UV Irradiation-Induced Cyclic-to-Linear Topological Changes of a Light/pH Dual-Sensitive Cyclic Copolymer for Enhanced Drug Delivery

Abstract

Cyclic polymers with cleavable backbones triggered by either external or internal stimuli can realize simultaneous extracellular stability and intracellular destabilization of cyclic polymer-based nanocarriers but remain seldom reported. To this end, we prepared herein cyclic-ONB-P(OEGMA-<i>st</i>-DMAEMA) (<i>c</i>-ONB-P(OEGMA-<i>st</i>-DMAEMA)) with a light-cleavable junction in the polymer backbone based on oligo (ethylene glycol) monomethyl ether methacrylate (OEGMA) and N,N-dimethylaminoethyl methacrylate (DMAEMA) using a light-cleavable atom transfer radical polymerization (ATRP) initiator containing an o-nitrobenzyl (ONB) ester group. Together with the pH-sensitivity of DMAEMA, <i>c</i>-ONB-P(OEGMA-<i>st</i>-DMAEMA) shows a light-cleavable mainchain and pH-sensitive side chains. Notably, doxorubicin (DOX)-loaded <i>c</i>-ONB-P(OEGMA₄-st-DMAEMA₃₈) (C2) micelles mediated an IC₅₀ value of 2.28 μg/mL in Bel-7402 cells, which is 1.7-fold lower than that acquired without UV irradiation. This study thus reported the synthesis of a cyclic copolymer with a UV-cleavable backbone and uncovered the effects of topological modulation on the in vitro controlled release properties of cyclic polymers.