Copolymer-Functionalized Cellulose Nanocrystals as a pH- and NIR-Triggered Drug Carrier for Simultaneous Photothermal Therapy and Chemotherapy of Cancer Cells.

Abstract

As a class of biocompatible and biodegradable naturally derived nanomaterials, cellulose nanocrystals (CNCs) with diverse surface functionalization have aroused considerable attention for a range of biomedical applications in drug or gene delivery, as a fluorescent nanoprobe, in cancer targeting, and in photothermal cancer therapy, among others. Herein, we construct the copolymer-functionalized CNCs as a pH- and near-infrared (NIR)-triggered drug carrier for simultaneous photothermal therapy and chemotherapy of cancer cells. Poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PCL-b-PDMAEMA) was conjugated onto the surface of CNCs through ring-opening polymerization, followed by activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP). The resultant CNC-based drug carrier can encapsulate doxorubicin (DOX) as a therapeutic agent and indocyanine green (ICG) as an NIR dye in the PCL core and the PDMAEMA shell, respectively, via hydrophobic and electrostatic interactions. In addition to the intrinsic pH response, the release profile of DOX can also be controlled by the duration of laser irradiation due to collapse of the crystal structure of the PCL domain with the increase of temperature induced by photothermal conversion. The drug carrier can exhibit enhanced cytotoxicity toward HepG2, human hepatocyte carcinoma, cells upon laser irradiation, which can be attributed to the synergistic effect arising from NIR-triggered burst release of DOX and photothermal heating. The rod-like morphology of the CNC-based drug carrier may help accelerate the endocytosis in cell membranes compared with its common spherical counterpart. Based on the abovementioned advantages, copolymer-functionalized CNCs can serve as a promising candidate for effective cancer treatment.