title: Investigation of size, surface charge, PEGylation degree and concentration on the cellular uptake of polymer nanoparticles.
abstract: In this work a large number of polymer nanoparticles (NPs) with different features have been synthesized through emulsion polymerization-based methods. Poly(methyl methacrylate) (PMMA), poly-ɛ-caprolactone (PCL), and poly(lactic acid) (PLA) based NPs with different size, hydrophobicity, surface charge, PEGylation degree, type of emulsifier and ζ potential have been produced and characterized. All the different NPs have been adopted for cellular uptake studies, leading to a precise quantification of the number of internalized NPs into a selected tumor cell line. The experiments summarize, emphasize and improve the comprehension of the influence of NPs features on the uptake efficiency. In detail, a linear relationship between uptake and both size and NP concentration independently upon other NP characteristics was found. Moreover, it was confirmed that cells are able to internalize and retain for a long time preferentially positively charged NPs. Finally, by coupling results of uptake studies with cell viability measurements, an easy and fast check to control the effectiveness of a selected polymer as drug carrier has been proposed. In particular, we observed that biodegradable PLA-based NPs with high molecular weight, non-PEGylated and positively charged PCL NPs are the better choice to maximize the uptake and minimize side effect against cells.
authors.affiliation: Department of Chemistry, Materials and Chemical Engineering, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ferrari
authors.affiliation: Department of Oncology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Lupi
authors.affiliation: Department of Chemistry, Materials and Chemical Engineering, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Colombo
authors.affiliation: Institute for Chemical and Bioengineering, ETH Zurich, CH-8093 Zurich, Switzerland.
authors.forename: Massimo
authors.initials: M
authors.lastname: Morbidelli
authors.affiliation: Department of Oncology, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, 20156 Milano, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Incalci
authors.affiliation: Department of Chemistry, Materials and Chemical Engineering, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy. Electronic address: davide.moscatelli@polimi.it.
authors.forename: Davide
authors.initials: D
authors.lastname: Moscatelli
mesh_terms: D004337:Drug Carriers / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters; D011108:Polymers / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide)
keywords: Drug delivery; Endocytosis; Imaging; Nanoparticle; Polymer; Uptake