EPR Cancer Research Results
EPR, enhanced permeability and retention (EPR) effect: Click to Expand ⟱
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Passive accumulation (in cells) is based on the unique architecture of the tumor tissue, where neo-angiogenesis leads to an atypical endothelial layer and to fenestrated vasculature, which together with the impaired lymphatic drainage guides the penetration and accumulation of nano-sized materials within the cancerous tissues.
Exploited for drug design in the nanomedicine field.
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Scientific Papers found: Click to Expand⟱
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in-vivo, |
Ovarian, |
A2780S |
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NA, |
Ovarian, |
SKOV3 |
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Fenton↑, Chemodynamic therapy (CDT) holds great promise in achieving cancer therapy through Fenton and Fenton-like reactions, which generate highly toxic reactive species
ROS↑, can decompose already existing intracellular H2O2 and produce reactive oxygen species (ROS) to attain a therapeutic outcome.
eff↑, Ag+, Fe2+) based silver pentacyanonitrosylferrate or silver nitroprusside (AgNP) were developed for Fenton like reactions that can specifically kills cancer cells by taking advantage of tumor acidic environment without used of any external stimuli
angioG↓, been reported that Ag-based materials are involved in angiogenesis inhibition by blocking Akt phosphorylation
p‑Akt↓,
EPR↑, These results indicate thatin cancer cell lines internalized AgNP, which partially localized inysosomes and could be relocalized to cytoplasm avoiding degradation due to lysosomal acidic pH, which produce ROS.
selectivity↑, While, in normal fibroblast cells over time AgNP colocalization in lysosomes increased due to the difference in lysosomal pH between cancer
and normal cells
selectivity↑, results suggest that AgNP specifically produces ROS in cancer cell lines due to high acidity in comparison to the normal cells.
eff↑, This specific ROS production is probably due to tumor
acidic environment in which AgNP act as a Fenton reagent
Cyt‑c↑, Cytochrome c release after AgNP treatment
HO-1↑, In A2780 cell line, HO-1 expression levels increased 8.1-fold when treated with AgNP
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in-vitro, |
GBM, |
U251 |
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in-vitro, |
GBM, |
U87MG |
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in-vitro, |
GBM, |
GL26 |
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in-vitro, |
Cerv, |
HeLa |
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in-vitro, |
CRC, |
RKO |
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AntiCan↑, Among the various NPs, silver nanoparticles (AgNPs) have garnered attention due to their cytotoxic and genotoxic properties in cancer cells.
eff↑, Our results demonstrate that UiO-66-NH2@AgNPs@Cis-Pt and its combinations exhibit enhanced cytotoxicity compared to individual components such as AgNPs and Cis-Pt.
EPR↑, Their nanometric structure allows them to easily penetrate and accumulate in tumour tissues either actively, via targeting systems [6,7,8], or passively, by taking advantage of tumour angiogenesis and the enhanced permeation and retention (EPR) effe
selectivity↑,
ROS↑, Once inside, AgNPs induce an increase in the production of reactive oxygen species (ROS) and cause mitochondrial dysfunctions, caspases activation, apoptosis, autophagy, and DNA damage
Casp↑,
Apoptosis↑,
DNAdam↑,
tumCV↓, figure 8
eff↑, One of the primary characteristics of AgNPs is their ability to release Ag+ ions from their surface in response to low pH or oxidation.
*Inflam↓, results showed a greater anti-inflammatory effect in the treatment with AgNPs, with a greater decrease in skin thickness when compared with the use of 1% hydrocortisone cream.
*EPR↑, higher permeability and retention of the nanoparticles in the edema area.
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in-vitro, |
BC, |
4T1 |
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in-vivo, |
BC, |
4T1 |
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in-vitro, |
Nor, |
3T3 |
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AntiCan↑, AgNPs have been demonstrated to exhibit anti-tumor effects through cell apoptosis.
ROS↑, ox-carried PA-AgNPs generate reactive oxidation species intensively beside 4T1 cells.
TumVol↓, in vivo study confirms that PA-AgNPs with Dox successfully inhibit tumors, which are about four times smaller than the control group and have high biosafety that can be applied for chemotherapy.
EPR↑, While all normal cells need enough vitamins to survive, cancer cells require a considerable number of vitamins to proliferate rapidly. As a result, the receptors on the cancer cell surface are overexpressed to capture as many vitamins as possible.
selectivity↑, PA-AgNPs (without/with Dox) concentrations ranging from 0 to 100 μg mL−1 did not seem to impair 3T3 cell viability due to poor uptake by normal cells.
ChemoSen↑, These results suggested that Dox-carried PA-AgNPs were both safer and more effective for cancer prevention.
EPR↑, cellular uptake of the AgNPs results indicated that the AgNPs accumulated within the cell.
BAX↑, Bax, Bcl-2, caspase-3 (CASP3), caspase-9 (CASP9)
Bcl-2↑,
Casp3↑,
Casp9↑,
DNAdam↑, apoptotic effects of the AgNPs through DNA fragmentation test, flow cytometry and cell cycle analysis indicated the induction of apoptosis in the A549 cell line.
TumCCA↑,
Apoptosis↑,
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Review, |
Var, |
NA |
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Review, |
Diabetic, |
NA |
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ROS↑, action mechanisms of AgNPs, which mainly involve the release of silver ions (Ag+), generation of reactive oxygen species (ROS), destruction of membrane structure.
eff↑, briefly introduce a new type of Ag particles smaller than AgNPs, silver Ångstrom (Å, 1 Å = 0.1 nm) particles (AgÅPs), which exhibit better biological activity and lower toxicity compared with AgNPs.
other↝, This method involves reducing silver ions to silver atoms 9, and the process can be divided into two steps, nucleation and growth
DNAdam↑, antimicrobial mechanisms of AgNPs includes destructing bacterial cell walls, producing reactive oxygen species (ROS) and damaging DNA structure
EPR↑, Due to the enhanced permeability and retention (EPR) effect, tumor cells preferentially absorb NPs-sized bodies than normal tissues
eff↑, Large surface area may lead to increased silver ions (Ag+) released from AgNPs, which may enhance the toxicity of nanoparticles.
eff↑, Our team prepared Ångstrom silver particles, capped with fructose as stabilizer, can be stable for a long time
TumMeta↓, AgNPs can induce tumor cell apoptosis through inactivating proteins and regulating signaling pathways, or blocking tumor cell metastasis by inhibiting angiogenesis
angioG↓, Various studies support that AgNPs can deprive cancer cells of both nutrients and oxygen via inhibiting angiogenesis
*Bacteria↓, Rather than Gram-positive bacteria, AgNPs show a stronger effect on the Gram-negative ones. This may be due to the different thickness of cell wall between two kinds of bacteria
*eff↑, In general, as particle size decreases, the antibacterial effect of AgNPs increases significantly
*AntiViral↑, AgNPs with less than 10 nm size exhibit good antiviral activity 185, 186, which may be due to their large reaction area and strong adhesion to the virus surface.
*AntiFungal↑, Some studies confirm that AgNPs exhibit good antifungal properties against Colletotrichum coccodes, Monilinia sp. 178, Candida spp.
eff↑, The greater cytotoxicity and more ROS production are observed in tumor cells exposed to high positive charged AgNPs
eff↑, Nanoparticles exposed to a protein-containing medium are covered with a layer of mixed protein called protein corona. formation of protein coronas around AgNPs can be a prerequisite for their cytotoxicity
TumCP↓, Numerous experiments in vitro and in vivo have proved that AgNPs can decrease the proliferation and viability of cancer cells.
tumCV↓,
P53↝, gNPs can promote apoptosis by up- or down-regulating expression of key genes, such as p53 242, and regulating essential signaling pathways, such as hypoxia-inducible factor (HIF) pathway
HIF-1↓, Yang et al. found that AgNPs could disrupt the HIF signaling pathway by attenuating HIF-1 protein accumulation and downstream target genes expression
TumCCA↑, Cancer cells treated with AgNPs may also show cell cycle arrest 160, 244
lipid-P↑, Ag+ released by AgNPs induces oxidation of glutathione, and increases lipid peroxidation in cellular membranes, resulting in cytoplasmic constituents leaking from damaged cells
ATP↓, mitochondrial function can be inhibited by AgNPs via disrupting mitochondrial respiratory chain, suppressing ATP production
Cyt‑c↑, and the release of Cyt c, destroy the electron transport chain, and impair mitochondrial function
MMPs↓, AgNPs can also inhibit the progression of tumors by inhibiting MMPs activity.
PI3K↓, Various studies support that AgNPs can deprive cancer cells of both nutrients and oxygen via inhibiting angiogenesis
Akt↓,
*Wound Healing↑, AgNPs exhibit good properties in promoting wound repair and bone healing, as well as inhibition of inflammation.
*Inflam↓,
*Bone Healing↑,
*glucose↓, blood glucose level of diabetic rats decreased when treated with AgNPs for 14 days and 21 days without significant acute toxicity.
*AntiDiabetic↑,
*BBB↑, The small-sized AgNPs are easy to penetrate the body and cross biological barriers like the blood-brain barrier and the blood-testis barrier
AntiCan↑, anti-cancer efficacy was observed against MCF-7 breast cancer cells having IC50 values of 53.36 ± 0.36 μg/mL (chitosan–ascorbic acid–glucose
EPR↑, we hypothesize that the nanoformulations can be up-taken readily by the cancer cells
pH↝, cancer cells are known to be acidic therefore the chitosan matrix can readily dissolve releasing the encapsulated components thereby triggering the subsequent death process in the cancerous cells
TumAuto↑, Overall, 10-nm AgNPs showed the highest cellular responses compared with 50- and 100-nm AgNPs . autophagy-lysosomal system
EPR↑, 10-nm AgNPs exhibited the highest uptake and accumulation.
LC3B↑, Subcytotoxic concentrations of AgNPs enhanced expression of LC3B, a pro-autophagic protein, and CHOP, an apoptosis inducing ER-stress protein, and activation of NLRP3-inflammasome (caspase-1, IL-1β).
CHOP↑,
ER Stress↑,
NLRP3↑,
Casp1↓,
ROS↑, Elucidation of the molecular mechanism revealed that bAgNPs induce cytotoxicity through elevation of reactive oxygen species (ROS) levels and induction of apoptosis.
Apoptosis↑,
eff↑, Interestingly, inhibition of autophagy increased the production of ROS, resulting in enhanced cell death
ChemoSen↑, bAgNPs Enhance Cytotoxicity of Chemotherapeutic Drug Cisplatin (CDDP)
EPR↑, The AgNPs were selected over free metal silver for exploration of their anticancerous effects because of the enhanced permeability of NPs into tumors, attributable to the EPR effect.
Casp↑, Induction of Apoptotic Cell Death by bAgNPs through Activation of Caspases
MAPK↑, Our results provide strong evidence for selective activation of MAPK pathways following AgNP exposure
ROS↑, At pharmacologic concentrations, ascorbate undergoes oxidation via ascorbate radical, generating cytotoxic
hydrogen peroxide (H₂O₂) through Fenton chemistry
Fenton↑,
BioAv↑, Although AsP is more stable than vitamin C, its poor release capacity and water insolubility limit its
bioavailability and therapeutic efficacy15,17. Thus, incorporating it into nanoparticle carriers can enhance circulation time and tumor accumulatio
EPR↑, Nanoparticles sized 30–200 nm enhance cell uptake via increased surface area
and membrane wrapping, effectively accumulating in tumors
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in-vivo, |
Melanoma, |
B16-F10 |
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Dose↝, we developed a dual drug delivery system to encapsulate ascorbyl palmitate (AP) and paclitaxel (PTX) for synergistic cancer therapy. 223 nm
TumCG↓, In vivo, AP/PTX-SLNs were revealed to be much more effective in suppressing tumor growth in B16F10-bearing mice and in eliminating cancer cells in the lungs
TumCP↓, AP has been found to inhibit the cell proliferation and DNA synthesis of various cancer cells, including breast, colon, glioblastoma, skin, and brain cancer cells (Naidu, 2003a).
BioAv↓, AP is limited due to its water insolubility, rapid degradation (accelerated by metal ions and/or light), and low bioavailability.
BioAv↑, Therefore, new technologies including nanoparticles that can enhance its delivery efficacy and reduce the dose of administration for Vc while not reducing its anti-cancer efficacy are highly desired.
other↑, These results conformed to the conclusion that only high doses of ascorbic acid have the ability to induce cancer cell death.
Apoptosis↑, Conclusively, the AP/PTX-SLNs exhibited a greater efficacy in inducing cell apoptosis by reducing the Bcl-2/Bax ratio accompanied by promoting tubulin polymerization
Bax:Bcl2↑,
EPR↑, such nanocarriers to permeate into tumor sites because of the enhanced permeation and retention (EPR) effect.
toxicity↝, AP/PTX synergistic combination-based SLN therapy did not induce toxicity and represents a promising strategy for paclitaxel/the vitamin C derivative in promoting anti-cancer effects.
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in-vivo, |
Lung, |
B16-F10 |
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vitro+vivo, |
Lung, |
A549 |
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in-vitro, |
BC, |
MDA-MB-231 |
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BioAv↓, major limitation of the compound includes poor bioavailability at the tumor site due to short plasma half-life.
Half-Life↓, Though BBM is a potent drug but its half-life in blood plasma is very short, owing to its quick renal clearance
eff↑, cellular experiments demonstrated enhanced therapeutic efficacy of BBM-NPs in inhibiting metastasis, cell proliferation and growth as compared to native BBM in highly metastatic cancer cell lines.
TumMeta↓,
TumCP↓,
TumCG↓,
Apoptosis↑, BBM shows its anticancer activity by induction of apoptosis, cell cycle arrest16 and reversing multidrug resistance17.
TumCCA↑,
MMP2↓, activation of MMP-2 &MMP-9 was suppressed effectively by BBM-NPs treated cells as compared to native BBM in both the cell lines
MMP9↓,
VEGF↓, the VEGF expression is lower in BBM-NPs treated case than that of native counterparts
Bcl-2↓, moderate down regulation of anti-apoptotic protein BCL-2 in BBM-NPs treated cells than that of native BBM treated case in both A549 and MDA-MB-231 cells
eff↑, BBM-NPs may be due to the enhanced accumulation of drug at the tumor site with sustained release phenomenon
EPR↑, The higher effectiveness of BBM-NPs may be attributed to the enhanced accretion of nanoparticulate drug at the tumor site with sustained release over a period of time, due to EPR effect
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Review, |
Nor, |
NA |
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Review, |
Stroke, |
NA |
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Review, |
AD, |
NA |
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*eff↑, borneol has shown superior ability for anti-inflammatory and analgesic activities when coupled with other active ingredients from ancient times.
BBB↑, Given its ability to enhance cross-barrier permeation
ChemoSen↑, interest in borneol, for various purposes, including anti-inflammatory, analgesic, neuronal protection, permeability promotion, chemotherapy sensitization and borneol-modified nano-drug delivery system
*Inflam↓, borneol and its synthetic counterpart exhibit noteworthy anti-inflammatory properties by reducing inflammatory factors, namely NO, TNF-α, and IL-6
*NO↓,
*TNF-α↓,
*IL6↓,
*Bacteria↓, Borneol has shown exceptional anti-bacterial effect activity and has been coupled in TCM formulas for external use against bacteria growth
*eff↑, Studies indicated that the combined administration of edaravone and borneol (i.e. Edaravone Dexborneol) exhibited synergistic effects in the treatment of ischemic stroke
*Aβ↓, efficient prohibition of the accumulation of Aβ in the brain
*SOD↑, Borneol has been reported to exhibit exceptional potential in the augmentation of superoxide dismutase (SOD) activity
*neuroP↑, Both naturally occurring and artificially synthesized borneol exhibited neuroprotective properties
*EPR↑, The permeation-enhancing effects of natural borneol and synthetic borneol on various drug properties have been observed,
toxicity↓, Borneol is an ideal absorption enhancer with low toxicity, little stimulation to gastrointestinal mucosa and strong permeability
P-gp↓, The inhibition of P-gp expression has been observed as a potential mechanism for reversing multidrug resistance, with borneol implicated in this process
eff↑, Research findings indicated that natural borneol can substantially enhance the anticancer properties of paclitaxel and curcumin.
other↝, specifically, the incorporation of borneol has been associated with improvements in drug solubility, enhanced cellular uptake, reduced organ toxicity, and mitigation of multiple drug resistances.
*toxicity↓, A comprehensive toxicological evaluation, including a 30-day rat study, demonstrated that borneol did not induce cytotoxicity, inflammation, or tissue damage at daily doses up to 270 mg/kg
*EPR↑, evaluate borneol as a permeation enhancer for improving the oral absorption of intact poly(lactic-co-glycolic acid) (PLGA) nanoparticles with different mean sizes (50-300 nm)
*other↑, Our findings establish borneol as a safe and effective oral permeation enhancer for intact nanocarriers, offering a viable strategy to enhance the oral bioavailability of therapeutics, particularly those encapsulated within small-sized NPs.
ChemoSen↑, combined treatment of NB and TMZ more effectively inhibited human glioma growth via triggering mitochondria-mediated apoptosis in vitro, accompanied by the caspase activation.
mt-Apoptosis↑,
Casp↑,
DNAdam↑, NB enhanced TMZ-induced DNA damage through inducing reactive oxide species (ROS) overproduction.
ROS↑,
angioG↓, anti-angiogenesis.
BBB↑, It is reported that NB could improve the oral bioavailability of anti-tumor drugs by regulating the permeability of the BBB.
EPR↑,
TumVol↓, combined treatment of NB and TMZ significantly inhibited tumor volume and tumor weight compared to that in treatment with NB or TMZ alone
TumW↓,
BioEnh↑,
TumMeta↓, We focus on the updated works of improving therapeutic efficacy, reducing toxicity, inhibiting tumor metastasis, reversing multidrug resistance, and enhancing brain targeting
BBB↑,
EPR↑, Nanocarriers can increase the concentration of a drug at the tumor site via the enhanced permeability and retention (EPR) effect, which also reduces systemic toxicity
toxicity↓,
BioAv↑, Moreover, borneol can promote the transdermal absorption of other drugs and increase their blood concentration and bioavailability
ChemoSen↑, application of borneol in nanocarriers has great potential to improve the targeting and enhance the accumulation of chemotherapeutic drugs in tumors.
eff↑, Borneol enhanced the antidepressant effects of asiaticoside by promoting its penetration of the BBB, thus enhancing the anti-depressant effects with enhanced 5-HT and BDNF, and reduced TNF-α levels
other↑, Borneol enhanced the antidepressant effects of asiaticoside by promoting its penetration of the BBB, thus enhancing the anti-depressant effects with enhanced 5-HT and BDNF, and reduced TNF-α levels
P-gp↓, inhibition of the function and expression of P-gp
MDR1↓, borneol could significantly inhibit the activity of drug resistance proteins such as multidrug resistance mutation 1 (MDR1) and P-gp and accelerate the transportation of drugs
ROS↑, chemotherapeutic sensitizer works along with the chemotherapeutic drugs to promote anticancer effect by increasing the level of reactive oxygen species (ROS) (119), arresting cell cycle (120)
TumCCA↑,
other↝, volatility of borneol makes it extremely unstable during preparation and storage.
BioAv↓, the poor water solubility of NB is not conducive to blood circulation, which greatly limits the effective delivery to the treatment site and greatly reduces its therapeutic effect.
DNAdam↑, lead to the activation of signaling pathways, including those involved in ROS, DNA damage, and apoptosis
BioEnh↑,
AntiCan↑, Several convergent studies show that capsaicin displays robust cancer activity, suppressing the growth, angiogenesis and metastasis of several human cancers.
TumCG↓,
angioG↓,
TumMeta↓,
BioAv↓, clinical applications of capsaicin as a viable anti-cancer drug have remained problematic due to its poor bioavailability and aqueous solubility properties
BioAv↓, capsaicin is associated with adverse side effects like gastrointestinal cramps, stomach pain, nausea and diarrhea and vomiting
BioAv↑, All these hurdles may be circumvented by encapsulation of capsaicin in sustained release drug delivery systems.
selectivity↑, Most importantly, these long-acting capsaicin formulations selectively kill cancer cells and have minimal growth-suppressive activity on normal cells.
EPR↑, The EPR effect is a mechanism by which high–molecular drug delivery systems (typically prodrugs, liposomes, nanoparticles, and macromolecular drugs) tend to accumulate in tumor tissue much more than they do in normal tissues
eff↓, The efficiency of such extravasation is maximum when the size of the liposomes less than 200 nm The CAP-CUR-GLY-GAL-LIPO were spherical in shape with a narrow range of size distribution ranging from 135–155nm
ChemoSen↑, The chemosensitization and anti-tumor activity of capsaicin involves multiple molecular pathways
Dose∅, oral, Intravenous (IV), and Intraperitoneal (IP) options
Half-Life∅, oral metabolized in 105mins, T1/2in blood=25mins.
eff↑, presence of urea (as a carrier) increased the aqueous solubility of capsaicin by 3.6-fold compared to pure capsaicin
DDS↑, Chitosan nanoparticles (CSNPs) have prospects as a revolutionary delivery system capable of enhancing anticancer drug activity and reducing negative impacts on normal cells.
BioAv↑, delivering materials to improve the bioactivity of NPs and to understand the intricacies of breast cancer has garnered significant interest.
EPR↑, Enhancement of the therapeutic efficacy of therapy, especially in tumor therapy, through passive targeting or enhanced permeation and retention (EPR) effects
TumCP↓, Inhibitory effects on tumor cell proliferation, tumor-associated angiogenesis, and metastasis, thus exhibiting good anticancer activity
angioG↓,
TumMeta↓,
other↑, The primary goal of modifying CS is to enhance its solubility, which may lead to a wider range of potential applications
*other↝, CS typically exhibits molecular weights ranging from 300 to 1000 kDa, influenced by its degree of acetylation.
*BioAv↓, Generally, CS is insoluble in water at neutral pH
eff↑, This pH-responsive solubility can be advantageous in drug delivery to specific regions of the body with varying pH levels
toxicity↓, It is non-toxic, biodegradable, and biocompatible.
eff↑, Owing to the favourable attributes of CS, it is widely used in the nanoencapsulation of EOs.
TumCD↑, CS nanoparticles have shown potent cytotoxic effects against human breast cancer MCF-7 cells with an IC50 ranging from 3.72 to 17.81 μg/mL after a 72 h incubation period.
Half-Life↑, It was reported that EO-loaded CS nanoparticles are able to circulate in the bloodstream for a relatively long time and accumulate at the cancer cell site
selectivity↑,
EPR↑, This can be achieved through the enhanced permeability and retention (EPR) effect.
ROS↑, Z. multiflora EO-loaded CS nanoparticles triggered the production of intracellular reactive oxygen species (ROS) in the mitochondria, which leads to apoptosis.
Apoptosis↑,
eff↑, CS-nanoencapsulated Citrus EOs exhibited improved cytotoxic properties against cancerous MDA-MB-468 cells.
eff↑, Formulated CSCur NPs were assessed for in-vitro release, which exhibited a sustained release pattern and four-fold higher cytotoxic activity in a nanoparticulated system.
EPR↑, Enhanced uptake, apoptotic effect of CSCur NPs were established by morphological changes in cells as observed by fluorescence microscopy and FE-SEM.
DNAdam↑, DNA damage, cell-cycle blockage and elevated ROS levels further confirm the anticancer activity of the CSCur NPs following apoptotic pathways.
TumCCA↑,
ROS↑,
toxicity↓, In-vivo study on Danio rerio, for uptake and toxicity reveal the particle's biocompatibility and nontoxicity
angioG↓, Both chitosan and its various derivatives have been reported to selectively permeate through the cancer cell membranes and show anticancer activity through the cellular enzymatic, antiangiogenic, immunoenhancing, antioxidant defense mechanism, and ap
*Imm↑,
*antiOx↑,
selectivity↑, They get sequestered from noncancer cells and provide their enhanced bioavailability in cancer cells in a sustained release manner.
other↝, The degree of deacetylation (DDA) of chitin ranges from 60 to 100 % and molecular weight of commercially obtained chitosan ranges from 3800 to 20,000 Daltons.
toxicity↓, The degree of deacetylation (DDA) of chitin ranges from 60 to 100 % and molecular weight of commercially obtained chitosan ranges from 3800 to 20,000 Daltons.
BioAv↑,
eff↝, exert anticancer activity with minimal toxicity on noncancer cells [13] and such activity against different cancer cell lines significantly depends upon molecular weight and DDA [
Half-Life↑, Sustained Release Mechanism
MPT↑, Chitosan MDA-MB-231 Permeation enhancement, lowering of MMP9 activity
MMP9↓,
lipid-P↑, induction of lipid peroxidation, enhanced permeation and retention (EPR) effect
EPR↑,
NK cell↑, Immunoenhancement through increase in activity of NK cells, T cells, killer lymphocytes and cytokins.
Casp3↑, Cellular apoptosis, activation of caspase-3 and caspase-8,
Casp8↑,
TumCCA↑, Cytokine signaling cell cycle arrest, ROS activation
ROS↑,
DDS↑, CMCS has been prepared as a carrier of anticancer drug such as 5- fluorouracil, curcumin, and doxorubicin
VEGF↓, decrease in VEGF level and increase in TIMP1 level after 14-day treatment of mouse serum with CMCS in vivo.
TIMP1↑,
ChemoSen↑, The paclitaxel loaded modified glycol chitosan nanoparticles in the size of 400 nm has been found to show sustained release of paclitaxel to bring about the inhibition of MCF-7 tumor growth due to EPR effect in vitro
eff↑, Chitosan-curcumin nanoformulation has been found to show anticancer activity following the apoptotic pathways associated with DNA damage, cell-cycle blockage, and elevation of ROS levels in vivo
DDS↑, attained promising recognition from researchers for improving the pharmacokinetics and pharmacodynamics of chemotherapeutics.
eff↓, CS-NPs for target-specific delivery of chemotherapeutics have also been considered.
*Bacteria↓, Owing to their inherent antimicrobial, antioxidant, wound healing, analgesic, anti-rheumatic, immunomodulatory, mucoadhesive, antiproliferative, and antimetastatic properties, CS and CS-NPs have been extensively investigated
*antiOx↑,
*Wound Healing↑,
*Imm↑,
TumCP↓,
TumMeta↓,
angioG↓, anticancer potential of CS and CS-NPs was attributed to their antiangiogenic, antioxidant, immunoenhancing, and apoptotic effects
Apoptosis↑,
ROS↑, apoptotic effect of CS-NPs is due to the generation of reactive oxygen species (ROS), which induce apoptosis and cause severe stress to the mitochondria and endoplasmic reticulum.
ER Stress↑,
BioAv↑, CS-NPs improve the rate and extent of absorption of chemotherapeutics from the site of administration owing to their prolonged residence time.
Half-Life↑,
eff↑, interesting approach employing high-intensity ultrasound was proposed by Choi et al35 to improve the penetration of CS-NPs into tumor tissues.
EPR↑, permeated CS-NPs were retained in tumor tissues for longer periods. This phenomenon is called “Enhanced Permeation and Retention (EPR)” effect.
ChemoSen↑, In addition to monodelivery, CS-NPs have shown tremendous potential for combined delivery of chemotherapeutics.
eff↑, CS-NPs have been conjugated with a variety of targeting ligands (eg, folic acid, hyaluronic acid, transferrin, antibodies, peptides, and aptamers) to enable selective intracellular delivery.
EPR↑, improved drug encapsulating efficiency. Extensively investigated for cancer treatment are CNPs, which improve chemotherapeutic tumor-targeting efficacy.
*BioAv↑, enhancing medication bioavailability especially for hydrophobic compounds
*eff↑, greater drug stability in acidic surroundings, which are common in the stomach
*other↝, Solubility is one of the key restrictions, as chitosan is only soluble in acidic settings, hence limiting its use in neutral or alkaline pH circumstances
*Insulin↑, chitosan-coated NPs raised insulin bioavailability by 3.5 times over that of free insulin
*Bacteria↓, Particularly in wound healing, infection control, and antimicrobial coatings, chitosan has inherent antibacterial qualities. Chitosan’s broad-spectrum antibacterial action has been demonstrated by many investigations.
eff↑, CNPs may be further functionalized with particular targeted ligands including folic acid, monoclonal antibodies, or peptides. Targeting moieties such as folic acid—which binds to folate receptors overexpressed on many cancer cells
ChemoSen↑, chitosan-based formulations enhanced by 50% the cellular absorption of DOX in comparison to free DOX, therefore boosting their therapeutic effectiveness.
TumCG↓, Compared with SeNPs, Cs-SeNPs more strongly inhibited 3D-tumor spheroid growth.
TumCMig↓, Cs-SeNPs exhibited stronger effects in inhibiting cell migration and cell invasion than SeNPs.
TumCI↓,
ChemoSen↑, Improved 5-FU sensitivity was observed in Cs-SeNP-treated cells.
*BBB↑, capability of coumarin-6 associated Cs-SeNPs to pass through the BBB was confirmed.
eff↑, nanotechnology plays a crucial role in developing selenium nanoparticles (SeNPs) to overcome this obstacle by reducing toxicity and improving biocompatibility
eff↑, result obviously indicates that Cs-SeNPs have a significantly higher positive charge than SeNPs; CS-SeNPs provided strong positive charges to the nanoparticles due to the positive charge of chitosan
eff↑, The size of SeNPs was also found to be greater than that of Cs-SeNPs
selectivity↑, 0.2% CS-SeNPs provided a large difference in toxicity between normal and cancer cells
MMP2↓, Cs-SeNPs Inhibited Cell Migration and Cell Invasion of Glioma Cells by Inhibiting MMP-2/9 Activities
MMP9↓,
EPR↑, Chitosan Coating Enhanced Cellular Uptake of Cs-SeNPs in U87 Cells
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in-vitro, |
Lung, |
A549 |
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in-vitro, |
Liver, |
HepG2 |
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EPR↑, A-coated chitosan NPs enhanced drug accumulation by effectively transporting NPs into CD44-overexpressed tumor cells, and they also resulted in mitochondrial damage induced by the production of reactive oxygen species (ROS).
mtDam↑,
ROS↑,
Apoptosis↑, Compared to free drug and uncoated NPs, HA-coated chitosan NPs exhibited stronger inhibition rates and induced obvious apoptosis in CD44-overexpressed A549 cells.
eff↑, Results suggest that high voltage, nsPEFs target the nucleus and modify cellular functions while plasma membrane effects are delayed and become smaller as pulse duration is shortened
EPR↑, electropermeabilization: if this voltage exceeds a critical value, generally assumed to be 1 V, structural changes in the cell membrane occur that cause the membrane to become more permeable to molecular transport.
other↝, Pulses of nanosecond rise-times and durations charge subcellular membranes, such as the nuclear envelope, in addition to the plasma membrane.
other↝, The study is designed to specifically explore the predicted shift of pulsed field effects from outer membrane to the nuclear membrane in the nanosecond pulse regime while the pulse duration is reduced.
Dose↝, A Blumlein pulse generator supplied the PEFs of 10 or 60 ns duration with voltages ranging from 0.1 to 1 k. This voltage corresponds to maximum electric fields in the suspension between 10 and 100 kV/cm.
Dose↝, The Blumlein generator consisted of two 50 X coaxial cables, which gave a total impedance of 100 X that matched the impedance of the cable pulse generator to the resistance of the cell suspension between the two electrodes.
Dose↝, The energy stored in the cables was transferred into the load by a rectangular pulse, with the pulse duration determined by the length of the cable and the speed of electromagnetic waves in the dielectric of the cable
eff↑, Ultrashort electric pulses target the nucleus
Morphological changes of the nucleus due to nsPEFs
were striking.
MMP↓, nsPEF bypasses plasma-membrane shielding to porate organelles, collapse mitochondrial potential, perturb ER calcium, and transiently open the nuclear envelope.
Ca+2↑,
eff↑, synergy with checkpoint blockade.
ER Stress↑, capacity to directly target organelles such as mitochondria, endoplasmic reticulum (ER),
selectivity↑, selectively ablate solid tumors, suppress metastatic spread, and prime systemic anti-tumor immunity while sparing adjacent normal tissue [7,9,10,11,12,13,14,15].
CSCs↓, Preclinical investigations have demonstrated that nsPEFs significantly reduce CSC-associated subpopulations, including CD44+/CD24− cells in breast cancer xenografts and CD133+ glioma stem-like cells
CD44↓,
CD133↓,
ROS↑, nsPEFs release Ca2+ from the ER, disrupt mitochondrial membrane potential, induce reactive oxygen species (ROS) generation, and perturb nuclear chromatin structure within nanoseconds
Imm↑, nsPEFs not only eliminate local tumor cells but also convert the tumor into an in situ vaccine, amplifying their therapeutic relevance in the era of immunotherapy
DNAdam↑, figure 2
MOMP↑, induce mitochondrial outer membrane permeabilization (MOMP)
Cyt‑c↑,
Casp9↑, Subsequent release of cytochrome c enables apoptosome assembly, caspase-9 activation, and downstream activation of caspases-3/7, culminating in cell death
Casp3↑,
Casp9↑,
TumCD↑,
Fas↑, In certain cell types, nsEP can also activate the extrinsic pathway, where Fas receptor clustering stimulates caspase-8.
UPR↑, This rapid surge triggers ER stress pathways, activates unfolded protein response (UPR) signaling, and promotes cross-talk with mitochondria through mitochondria-associated membranes (MAMs)
Dose↝, longer ns pulses (100–300 ns) generate sustained plasma membrane charging, resulting in robust Ca2+ influx, osmotic imbalance, and apoptotic priming.
Dose↝, A critical threshold of 10–20 kV/cm is generally required to initiate pore formation in malignant cells, with higher amplitudes (>30–40 kV/cm) producing more extensive permeabilization [100].
Dose↓, Low pulse counts (<100) frequently produce reversible stress responses, such as transient mitochondrial depolarization or ER Ca2+ release, without committing cells to apoptosis. I
Dose↑, In contrast, higher pulse counts (500–1000) lead to irreversible apoptosis, caspase activation, and release of DAMPs that initiate ICD [80,106].
HMGB1↓, ICD after nsPEF is characterized by surface exposure of calreticulin, extracellular ATP release, and HMGB1 emission
eff↑, The integration of nsPEFs with NP-based systems thus represents a synergistic platform where physical membrane poration and molecular targeting cooperate to maximize therapeutic efficacy.
EPR↑, demonstrates that PEF + AuNPs enhanced membrane permeabilization compared with PEF alone,
ChemoSen↑, The superior efficacy of delayed drug administration following nsPEF exposure can be attributed to transient biophysical and biochemical changes that persist after pulsing.
ETC↝, study demonstrated that nsPEFs dynamically alter trans-plasma membrane electron transport (tPMET) and mitochondrial electron transport chain activity, resulting in differential ROS generation in cancer versus non-cancer cells (Figure 9).
*AntiAge↑, Mechanistically, nsPEFs upregulated HIF-1α and SIRT1, mediators of mitochondrial retrograde signaling, thereby reversing hallmarks of aging
*Hif1a↑,
*SIRT1↑,
EPR↑, AuNPs were modified via single-phase emulsification to form a nanoemulsion coated with a hydrophobic AsP layer, improving tumor targeting through the enhanced permeability and retention (EPR) effect.
eff↑, The Au-GEM-AsP-COV formulation demonstrated superior hydrophobicity, sustained release, and enhanced cytotoxicity (IC50 of 0.44 µg/mL) in the 4T1 cell line, significantly outperforming free GEM and modified Au-GEM formulations.
RadioS↑, Specifically, numerous NPs, particularly gold NPs (AuNPs) and hafnium oxide (HfO2) NPs (such as NBTXR3), have been shown to substantially augment the local radiation dose
EPR↑, Functionalized NPs have the capability to preferentially accumulate in tumor tissues via the enhanced permeability and retention (EPR) effect, thereby minimizing adverse effects on healthy tissues and enhancing the specificity of therapeutic interve
ROS↑, encompass enhanced ROS generation, inhibition of hypoxia, targeted radiation, improvement of the tumor immune microenvironment, and induction of G2/M cell cycle arrest (Table 1)
TumCCA↑,
AntiTum↑, frequency below 300 Hz) exert anti-tumor function, independent of thermal effects
TumCG↓, Magnetic fields (MFs) could inhibit cell growth and proliferation; induce cell cycle arrest, apoptosis, autophagy, and differentiation; regulate the immune system; and suppress angiogenesis and metastasis via various signaling pathways
TumCCA↑,
Apoptosis↑,
TumAuto↑,
Diff↑,
angioG↓,
TumMeta↓,
EPR↑, MFs not only promote the absorption of chemotherapy drugs by producing small holes on the surface of cell membrane
ChemoSen↑,
ROS↑, MF treatment has been shown to promote the generation of ROS in many studies (31, 71, 72), with exposure within a 60 Hz sinusoidal MF for 48 h in induced human prostate cancer for DU145, PC3, and LNCaP apoptoses
DNAdam↑, Repetitive exposure to LF-MFs induced DNA damage and accumulation of DSBs and triggered apoptosis in Hela and MCF7 cell lines
P53↑, PMFs could trigger apoptosis cell death by upregulating the p53 level and through the mitochondrial-dependent pathway
Akt↓, LF-MFs (300 mT, 6 Hz, 24 h) also induced apoptosis by suppressing protein kinase B (Akt) signaling, activating p38 mitogen-activated protein kinase (MAPK) signaling, and caspase-9, which is the executor of the mitochondrial apoptosis pathway
MAPK↑,
Casp9↑,
VEGFR2↓, reducing the expression and activation levels of VEGFR2
P-gp↓, A combination with the SMF (8.8 m T, 12 h) decreased the expression of P-glycoprotein (P-gp) in K562 cancer cells, while adriamycin itself induced an increase
| - |
vitro+vivo, |
NA, |
MCF-7 |
|
|
|
- |
vitro+vivo, |
NA, |
A549 |
|
|
|
TumCG↓, growth inhibition (∼5%)
TumVol↓, 9% for PMF2
Casp3↑,
Casp7↑,
Apoptosis↑,
DNAdam↑,
TumCCA↑,
ChemoSen↑, PEMF synergistically enhances the potency of chemotherapy agents such as doxorubicin, 17 vincristine, 18 mitomycin C, 18 cisplatin, 18 and actinomycin.
EPR↑, PEMF can increase cell permeability. longer PEMF exposure may be required to increase cell membrane permeability.
*ROS↓, Moreover, it is a cofactor of anti-oxidant enzymes (glutathione peroxidase and thioredoxin reductase) that safeguards our human body from reactive oxygen species (ROS).
*BioAv↑, SeNPs have displayed stupendous properties which have resulted in their maximum utilization for various crucial applications. They are biocompatible and exhibit excellent bioavailability, high affinity, biological activity, good permeability, and int
*antiOx↑, and intestinal absorption, as well as anti-oxidant activities
toxicity↓, NPs have lower toxicity than inorganic Se and other organoselenium compound
eff↑, This is because only a single-step reduction from the elemental selenium atom to selenide anion is required to activate redox cycling with oxygen to produce ROS while multiple-step reduction is necessary for selenite
*other↝, SeNPs are normally unstable in the liquid phase and extremely easy to aggregate which results in the formation of gray or black selenium with a large particle size.
EPR↑, It has been discovered that NPs of sizes ranging between 10 and 100 nm can penetrate deep into the tumor tissues and destroy cancer cells without affecting healthier ones, an effect termed as “enhanced permeation and retention”
selectivity↑,
eff↑, Amidst the efficient nanoparticle family, SeNPs have excelled in proving to be one of the best NPs available for cancer therapy.
RadioS↑, SeNPs (act as a radiosensitizer) were not affected by radiation instead a greater concentration of intracellular Se ions was induced, leading to an increase in its toxicity by rapid generation of free radicals.
eff↑, Small-sized SeNPs exhibited greater inhibition of cancer cell progression through the ROS-mediated system, and no side effects were observed on increasing selenoenzyme activities.
*Bacteria↓, Reports have demonstrated the exemplary features of SeNPs that enable them to be a powerful anti-microbial agent
Showing Research Papers: 1 to 32 of 32
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 32
Pathway results for Effect on Cancer / Diseased Cells:
Redox & Oxidative Stress ⓘ
Fenton↑, 2, HO-1↑, 1, lipid-P↑, 2, ROS↑, 16,
Mitochondria & Bioenergetics ⓘ
ATP↓, 1, ETC↝, 1, MMP↓, 1, MPT↑, 1, mtDam↑, 1,
Cell Death ⓘ
Akt↓, 2, p‑Akt↓, 1, Apoptosis↑, 10, mt-Apoptosis↑, 1, BAX↑, 1, Bax:Bcl2↑, 1, Bcl-2↓, 1, Bcl-2↑, 1, Casp↑, 3, Casp1↓, 1, Casp3↑, 4, Casp7↑, 1, Casp8↑, 1, Casp9↑, 4, Cyt‑c↑, 3, Fas↑, 1, MAPK↑, 2, MOMP↑, 1, TumCD↑, 2,
Transcription & Epigenetics ⓘ
other↑, 3, other↝, 6, tumCV↓, 2,
Protein Folding & ER Stress ⓘ
CHOP↑, 1, ER Stress↑, 3, UPR↑, 1,
Autophagy & Lysosomes ⓘ
LC3B↑, 1, TumAuto↑, 2,
DNA Damage & Repair ⓘ
DNAdam↑, 9, P53↑, 1, P53↝, 1,
Cell Cycle & Senescence ⓘ
TumCCA↑, 9,
Proliferation, Differentiation & Cell State ⓘ
CD133↓, 1, CD44↓, 1, CSCs↓, 1, Diff↑, 1, PI3K↓, 1, TumCG↓, 6,
Migration ⓘ
Ca+2↑, 1, MMP2↓, 2, MMP9↓, 3, MMPs↓, 1, TIMP1↑, 1, TumCI↓, 1, TumCMig↓, 1, TumCP↓, 5, TumMeta↓, 7,
Angiogenesis & Vasculature ⓘ
angioG↓, 8, EPR↑, 29, HIF-1↓, 1, VEGF↓, 2, VEGFR2↓, 1,
Barriers & Transport ⓘ
BBB↑, 3, P-gp↓, 3,
Immune & Inflammatory Signaling ⓘ
HMGB1↓, 1, Imm↑, 1, NK cell↑, 1,
Cellular Microenvironment ⓘ
pH↝, 1,
Protein Aggregation ⓘ
NLRP3↑, 1,
Drug Metabolism & Resistance ⓘ
BioAv↓, 5, BioAv↑, 7, BioEnh↑, 2, ChemoSen↑, 13, DDS↑, 3, Dose↓, 1, Dose↑, 1, Dose↝, 6, Dose∅, 1, eff↓, 2, eff↑, 34, eff↝, 1, Half-Life↓, 1, Half-Life↑, 3, Half-Life∅, 1, MDR1↓, 1, RadioS↑, 2, selectivity↑, 10,
Functional Outcomes ⓘ
AntiCan↑, 4, AntiTum↑, 1, toxicity↓, 6, toxicity↝, 1, TumVol↓, 3, TumW↓, 1,
Total Targets: 91
Pathway results for Effect on Normal Cells:
Redox & Oxidative Stress ⓘ
antiOx↑, 3, ROS↓, 1, SOD↑, 1,
Mitochondria & Bioenergetics ⓘ
Insulin↑, 1,
Core Metabolism/Glycolysis ⓘ
glucose↓, 1, SIRT1↑, 1,
Transcription & Epigenetics ⓘ
other↑, 1, other↝, 3,
Angiogenesis & Vasculature ⓘ
EPR↑, 3, Hif1a↑, 1, NO↓, 1,
Barriers & Transport ⓘ
BBB↑, 2,
Immune & Inflammatory Signaling ⓘ
IL6↓, 1, Imm↑, 2, Inflam↓, 3, TNF-α↓, 1,
Protein Aggregation ⓘ
Aβ↓, 1,
Drug Metabolism & Resistance ⓘ
BioAv↓, 1, BioAv↑, 2, eff↑, 4,
Clinical Biomarkers ⓘ
IL6↓, 1,
Functional Outcomes ⓘ
AntiAge↑, 1, AntiDiabetic↑, 1, Bone Healing↑, 1, neuroP↑, 1, toxicity↓, 1, Wound Healing↑, 2,
Infection & Microbiome ⓘ
AntiFungal↑, 1, AntiViral↑, 1, Bacteria↓, 5,
Total Targets: 30
Scientific Paper Hit Count for: EPR, enhanced permeability and retention (EPR) effect
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include :
-low or high Dose
-format for product, such as nano of lipid formations
-different cell line effects
-synergies with other products
-if effect was for normal or cancerous cells
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