title: Sub-100 nm biodegradable nanoparticles: in vitro release features and toxicity testing in 2D and 3D cell cultures.
abstract: A big challenge in tumor targeting by nanoparticles (NPs), taking advantage of the enhanced permeability and retention effect, is the fabrication of small size devices for enhanced tumor penetration, which is considered fundamental to improve chemotherapy efficacy. The purposes of this study are (i) to engineer the formulation of doxorubicin-loaded poly(D,L-lactic-co-glycolic acid) (PLGA)-block-poly(ethylene glycol) (PEG) NPs to obtain <100 nm devices and (ii) to translate standard 2D cytotoxicity studies to 3D collagen systems in which an initial step gradient of the NPs is present. Doxorubicin release can be prolonged for days to weeks depending on the NP formulation and the pH of the release medium. Sub-100 nm NPs are effectively internalized by HeLa cells in 2D and are less cytotoxic than free doxorubicin. In 3D, <100 nm NPs are significantly more toxic than larger ones towards HeLa cells, and the cell death rate is affected by the contributions of drug release and device transport through collagen. Thus, the reduction of NP size is a fundamental feature from both a technological and a biological point of view and must be properly engineered to optimize the tumor response to the NPs.
authors.affiliation: Dipartimento di Chimica Farmaceutica e Tossicologica, Facoltà di Farmacia, Università di Napoli Federico II, Via Domenico Montesano 49, Napoli, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Biondi
authors.forename: Daniela
authors.initials: D
authors.lastname: Guarnieri
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.forename: Valentina
authors.initials: V
authors.lastname: Belli
authors.forename: Paolo Antonio
authors.initials: PA
authors.lastname: Netti
mesh_terms: D020341:Absorbable Implants; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008422:Materials Testing; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D053769:Nanocapsules; D004317:Doxorubicin