title: Cellular Uptake and Cytotoxic Effect of Epidermal Growth Factor Receptor Targeted and Plitidepsin Loaded Co-Polymeric Polymersomes on Colorectal Cancer Cell Lines.
abstract: Encapsulating chemotherapy drugs in targeted nanodelivery systems is one of the most promising approaches to tackle cancer disease, avoiding side effects of common treatment. In the last decade, several nanocarriers with different nature have been tested, but polypeptide-based copolymers have attracted considerable attention for their biocompatibility, controlled and slow biodegradability as well as their low toxicity. In this work, we synthesized, characterized and evaluated poly(trimethylene carbonate)-bock-poly(L-glutamic acid) derived polymersomes, targeted to epidermal growth factor receptor (EGFR), loaded with plitidepsin and ultimately tested in HT29 and LS174T colorectal cancer cell lines for specificity and efficacy. Furthermore, morphology, physico-chemical properties and plitidepsin loading were carefully investigated. A thorough in vitro cytotoxicity analysis of the unloaded polymersomes was carried out for biocompatibility check, studying viability, cell membrane asymmetry and reactive oxygen species levels. Those cytotoxicity assays showed good biocompatibility for plitidepsin-unloaded polymersomes. Cellular uptake and cytotoxic effect of EGFR targeted and plitidepsin loaded polymersome indicated that colorectal cancer cell lines were.more sensitive to anti-EGFR-drug-loaded than untargeted drug-loaded polymersomes. Also, in both cell lines, the use of untargeted polymersomes greatly reduced plitidepsin cytotoxicity as well as the cellular uptake, indicating that the use of this targeted nanocarrier is a promising approach to tackle colorectal cancer disease and avoid the undesired effects of the usual treatment. Furthermore, in vivo assays support the in vitro conclusions that EGFR targeted polymersomes could be a good drug delivery system. This work provides a proof of concept for the use of encapsulated targeted drugs as future therapeutic treatments for cancer.
authors.forename: Felipe
authors.initials: F
authors.lastname: Goñi-de-Cerio
authors.forename: Julie
authors.initials: J
authors.lastname: Thevenot
authors.forename: Hugo
authors.initials: H
authors.lastname: Oliveira
authors.forename: Encarnación
authors.initials: E
authors.lastname: Pérez-Andrés
authors.forename: Edurne
authors.initials: E
authors.lastname: Berra
authors.forename: Marc
authors.initials: M
authors.lastname: Masa
authors.forename: Blanca
authors.initials: B
authors.lastname: Suárez-Merino
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lecommandoux
authors.forename: Pedro
authors.initials: P
authors.lastname: Heredia
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000378:metabolism*; D047630:Depsipeptides / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D004146:Dioxanes / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009336:Necrosis; D010456:Peptides, Cyclic; D011099:Polyglutamic Acid / Q000737:chemistry / Q000493:pharmacokinetics*; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; D004146:Dioxanes; D004337:Drug Carriers; D010456:Peptides, Cyclic; D011108:Polymers; D011099:Polyglutamic Acid; C059299:polytrimethylene carbonate; C512478:EGFR protein, human; D066246:ErbB Receptors; C098980:plitidepsin