Enhanced permeability and retention (EPR) effect for anticancer nanomedicine drug targeting.
Effective cancer therapy remains one of the most challenging tasks to the scientific community, with little advancement on overall cancer survival landscape during the last two decades. A major limitation inherent to most conventional anticancer chemotherapeutic agents is their lack of tumor selectivity. One way to achieve selective drug targeting to solid tumors is to exploit abnormalities of tumor vasculature, namely hypervascularization, aberrant vascular architecture, extensive production of vascular permeability factors stimulating extravasation within tumor tissues, and lack of lymphatic drainage. Due to their large size, nano-sized macromolecular anticancer drugs administered intravenously (i.v.) escape renal clearance. Being unable to penetrate through tight endothelial junctions of normal blood vessels, their concentration builds up in the plasma rendering them long plasma half-life. More importantly, they can selectively extravasate in tumor tissues due to its abnormal vascular nature. Overtime the tumor concentration will build up reaching several folds higher than that of the plasma due to lack of efficient lymphatic drainage in solid tumor, an ideal application for EPR-based selective anticancer nanotherapy. Indeed, this selective high local concentration of nano-sized anticancer drugs in tumor tissues has proven superior in therapeutic effect with minimal side effects in both preclinical and clinical settings.
Greish
Khaled
K
Department of Pharmaceuticals and Pharmaceutical Chemistry, and Utah Center for Nanomedicine, University of Utah, Salt Lake City, UT, USA.
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D004354:Drug Screening Assays, Antitumor; D008297:Male; D008298:Maleates / Q000737:chemistry; D051379:Mice; D008823:Micelles; D008954:Models, Biological; D050997:Nanomedicine / Q000379:methods*; D009369:Neoplasms / Q000628:therapy*; D010539:Permeability / Q000187:drug effects; D011137:Polystyrenes / Q000737:chemistry; D014018:Tissue Distribution / Q000187:drug effects
D000970:Antineoplastic Agents; D008298:Maleates; D008823:Micelles; D011137:Polystyrenes; C024074:styrene-maleic acid polymer; D004317:Doxorubicin