Folate-induced nanostructural changes of oligochitosan nanoparticles and their fate of cellular internalization by melanoma

• Published in: Carbohydrate Polymers
• Main Author: Musalli A.H.; Talukdar P.D.; Roy P.; Kumar P.; Wong T.W.
• Format: Article
• Language: English
• Published: Elsevier Ltd 2020
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85085738172&doi=10.1016%2fj.carbpol.2020.116488&partnerID=40&md5=b29ede575b5441ec6b656b74cca9af37

This study examined the effects of folate environment of oligochitosan nanoparticles on their cellular internalization profiles in human melanoma cells. The conjugates and nanoparticles of oligochitosan-folate, oligochitosan-carboxymethyl-5-fluorouracil, and oligochitosan-folate-carboxymethyl-5-fluorouracil were synthesized by carbodiimide chemistry and prepared by nanospray drying technique respectively. The cellular internalization profiles of oligochitosan-folate nanoparticles against the human malignant melanoma cell line (SKMEL-28) were evaluated using confocal scanning electron microscopy technique through fluorescence labelling and endocytic inhibition, as a function of nanoparticulate folate content, size, polydispersity index, zeta potential, shape, surface roughness and folate population density. The cytotoxicity and cell cycle arrest characteristics of oligochitosan-folate-carboxymethyl-5-fluorouracil nanoparticles, prepared with an optimal folate content that promoted cellular internalization, were evaluated against the oligochitosan-folate and oligochitosan-carboxymethyl-5-fluorouracil conjugate nanoparticles. The oligochitosan-folate conjugate nanoparticles were endocytosed by melanoma cells via caveolae- and lipid raft-mediated endocytic pathways following them binding to the cell surface folate receptor. Nanoparticles that were larger and with higher folic acid contents and zeta potentials exhibited a higher degree of cellular internalization. Excessive conjugation of nanoparticles with folate resulted in a high nanoparticulate density of folate which hindered nanoparticles-cell interaction via folate receptor binding and reduced cellular internalization of nanoparticles. Conjugating oligochitosan with 20 %w/w folate was favorable for cellular uptake as supported by in silico models. Conjugating of oligochitosan nanoparticles with carboxymethyl-5-fluorouracil and 20 %w/w of folate promoted nanoparticles-folate receptor binding, cellular internalization and cancer cell death via cell cycle arrest at S phase at a lower drug dose than oligochitosan-carboxymethyl-5-fluorouracil conjugate nanoparticles and neat carboxymethyl-5-fluorouracil. © 2020 Elsevier Ltd