Smart nanocarrier from norbornene based triblock copolymers for the sustained release of multi-cancer drugs

Abstract

A stimuli responsive, multi-anticancer drug derived nanocarrier has been synthesized by conjugating doxorubicin, chlorambucil, folate to the backbone of a norbornene polymer. Monomers namely NOR–DOX (mono 1), NOR–CHO (mono 2), and norbornene grafted poly(ethyleneglycol)–folate NOR–PEG–FOL (mono 3), are connected to the norbornene backbone by ester linkers to demonstrate the pH responsive capabilities. The complete chemical and biological properties of the nanocarriers, intended for combination cancer chemotherapy, are discussed. This nanocarrier, DOX–CHO–FOL is designed in such a way that doxorubicin, and chlorambucil, are both conjugated to the same polymer. The presence of the PEG–FOL functionality makes the system water-soluble as well as site-specific. The nanocarrier capabilities are tested by dynamic light scattering, scanning electron and transmission electron microscopies. The drug release profile shows the importance of having the ester linker which helps the drug at the mild acidic conditions resembling the pH of the cancerous cells. Confocal microscope studies confirm the cell internalization of the nanocarrier. MTT assay against 4T cells suggests the importance of the nanocarrier in the anticancer efficacy.