Exploiting the enhanced permeability and retention effect for tumor targeting

Iyer, Arun K.; Greish, Khaled; Fang, Jun; Maeda, Hiroshi

doi:10.1016/j.drudis.2006.07.005

Cited by 1,660 publications

(1,194 citation statements)

References 58 publications

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“…The tumor vasculature, characterized by irregularly shaped, dilated, defective, and/or leaky blood vessels, disorganized endothelial cells with fenestrations, as well as other abnormalities, allows for the passive accumulation of macromolecules at the tumor site [24]. Further, due to the poor lymphatic drainage, nanoparticles can accumulate and remain at the tumor site even in the absence of a targeting moiety [25].…”

Section: Introductionmentioning

confidence: 99%

“…Further, due to the poor lymphatic drainage, nanoparticles can accumulate and remain at the tumor site even in the absence of a targeting moiety [25]. This phenomenon is known as the enhanced permeability and retention (EPR) effect and makes it possible to achieve high local concentrations of macromolecules at the tumor site without specific targeting [24]. However, a question that has yet to be addressed with polymersomes is how much additional accumulation is possible with targeting.…”

Section: Introductionmentioning

confidence: 99%

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Polymersomes: A new multi-functional tool for cancer diagnosis and therapy

Levine

Ghoroghchian

Freudenberg

et al. 2008

Methods

198

122

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Nanoparticles are being developed as delivery vehicles for therapeutic pharmaceuticals and contrast imaging agents. Polymersomes (mesoscopic polymer vesicles) possess a number of attractive biomaterial properties that make them ideal for these applications. Synthetic control over block copolymer chemistry enables tunable design of polymersome material properties. The polymersome architecture, with its large hydrophilic reservoir and its thick hydrophobic lamellar membrane, provides significant storage capacity for both water soluble and insoluble substances (such as drugs and imaging probes). Further, the brush-like architecture of the polymersome outer shell can potentially increase biocompatibility and blood circulation times. A further recent advance is the development of multi-functional polymersomes that carry pharmaceuticals and imaging agents simultaneously. The ability to conjugate biologically active ligands to the brush surface provides a further means for targeted therapy and imaging. Hence, polymersomes hold enormous potential as nanostructured biomaterials for future in vivo drug delivery and diagnostic imaging applications.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polymersomes: A new multi-functional tool for cancer diagnosis and therapy

Levine

Ghoroghchian

Freudenberg

et al. 2008

Methods

198

122

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“…Furthermore, nano-size of micelles makes them passively targeted to tumors by the enhanced permeability and retention (EPR) effect, improving their antitumor effects. [21][22][23] In this work, chetomin was obtained by fermentation using Chaetomium cochliodes (C. 3.198), and chetomin-loaded polymeric micelles (Che-M) were prepared by using a solid dispersion method. When the concentration of copolymer was higher than the critical gelation concentration, the Che-M could form a thermosensitive hydrogel (Che-H), which was a free-owing sol at ambient temperature and converted into a non-owing gel at body temperature.…”

Section: Introductionmentioning

confidence: 99%

Enhanced antitumor activity and mechanism of biodegradable polymeric micelles-encapsulated chetomin in both transgenic zebrafish and mouse models

Deng

et al. 2014

Nanoscale

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Chetomin is a promising molecule with anti-tumor activities in the epipolythiodioxopiperazine family of fungal secondary metabolites; however, strong hydrophobicity has limited its further applications. In this work, chetomin was encapsulated into polymeric micelles to obtain an aqueous formulation, and the chetomin loaded micelles (Che-M) exhibited small particle size and high encapsulation efficiency. When the concentration of copolymer was higher than the critical gelation concentration, the Che-M could form a thermosensitive hydrogel (Che-H), which was free-flowing sol at ambient temperature and converted into a non-flowing gel at body temperature. The molecular modeling study has indicated that chetomin interacted with PCL as a core, which was embraced by PEG as a shell. Che-M showed equal cytotoxicity with free chetomin, but the apoptosis inducing effects of Che-M were more significant.Besides, Che-M could increase the GSSG level, decrease the GSH level, and increase the ROS in CT26 cells. Furthermore, stronger inhibitory effects of Che-M were observed on embryonic angiogenesis, tumor-induced angiogenesis and tumor growth in transgenic zebrafish models. In addition, Che-M was effective in inhibiting tumor growth and prolonging survival in a subcutaneous CT26 tumor model. In a colorectal peritoneal carcinomatosis model, both Che-M and Che-H showed excellent therapeutic effects, but Che-H was more effective. In conclusion, Che-M and Che-H may serve as candidates for cancer therapy.

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“…Anticancer drugs have some limitations as low stability and half-life, bioavailability that can be minimized using nanoparticles (Iyer et al 2006;Beija et al 2012;Liu et al 2012). Several studies showed that polymeric nanoparticles are suitable nanocarriers due to their high capacity of drug encapsulation and endocytosis efficiency by enhanced permeation and retention (EPR) effect (Garnett and Kallinteri 2006;Lee et al 2013;Sinha et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Encapsulation of a proteasome inhibitor with gold-polysaccharide nanocarriers

et al. 2014

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Designing positively charged chitosan-gum arabic-gold nanoparticle structures is farsighted to be a new approach to specific drug delivery. To reconnoitre this concept, an anticancer drug activity was evaluated with a proteasome inhibitor, bortezomib, in pancreatic cell lines, S2-013 and hTERT-HPNE. Laser scanning confocal microscopy show the uptake of the gold nanoparticle/bortezomib encapsulated in chitosan-gum arabic matrix and the fast internalization of these nanocombinations into pancreatic cells. Cytotoxic assays assessed that positively charged nanosystems reduce the cell growth and cell proliferation of S2-013s but the same effect was not observed in cytotoxic response in hTERT-HPNE cells. The findings of this study show the capacity of chitosan-gum arabic nanocarriers to deliver gold nanoparticles/anticancer drug and to increase the permeation and retention effect in S2-013 cells and minimize drug side effects in HPNE cells.

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Exploiting the enhanced permeability and retention effect for tumor targeting

Cited by 1,660 publications

References 58 publications

Polymersomes: A new multi-functional tool for cancer diagnosis and therapy

Polymersomes: A new multi-functional tool for cancer diagnosis and therapy

Enhanced antitumor activity and mechanism of biodegradable polymeric micelles-encapsulated chetomin in both transgenic zebrafish and mouse models

Encapsulation of a proteasome inhibitor with gold-polysaccharide nanocarriers

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