Fate of PLA and PCL-Based Polymeric Nanocarriers in Cellular and Animal Models of Triple-Negative Breast Cancer

• Published in: Biomacromolecules 2016-03, Vol.17 (3), p.744-755
• Main Authors: Sitia, Leopoldo, Ferrari, Raffaele, Violatto, Martina B., Talamini, Laura, Dragoni, Luca, Colombo, Claudio, Colombo, Laura, Lupi, Monica, Ubezio, Paolo, D’Incalci, Maurizio, Morbidelli, Massimo, Salmona, Mario, Moscatelli, Davide, Bigini, Paolo
• Format: Article
• Language: English
• Subjects: Animals; Cell Line, Tumor; Drug Carriers - adverse effects; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Female; Humans; Mice; Nanocapsules - adverse effects; Nanocapsules - chemistry; Polyesters - chemistry; Tissue Distribution; Triple Negative Breast Neoplasms - drug therapy
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/acs.biomac.5b01422

An integrated platform to assess the interaction between nanocarriers and biological matrices has been developed by our group using poly methyl-methacrylate nanoparticles. In this study, we exploited this platform to evaluate the behavior of two biodegradable formulations, poly-ε-caprolactone (PCL3) and poly lactic-acid (PLA8), respectively, in cellular and animal models of triple-negative breast cancer (TNBC). Both NPs shared the main physicochemical parameters (size, shape, ζ-potential) and exclusively differentiated on the material on which they are composed. Our results showed that (1) PLA8 NPs, systemically injected in mice, underwent rapid degradation without penetration into tumors; (2) PLA8 NPs were not internalized in the human TNBC cell line (MDA-MB-231); (3) PCL3 NPs had a longer bioavailability, reached the tumor parenchyma, and efficiently penetrated in MDA-MB-231 cells. Our data highlight the relevance of the material selection to both improve bioavailability and target tropism, and make PCL3 NPs an interesting tool for the development of nanodrugs against TNBC.