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-st-DMAEMA) (c-ONB-P(OEGMA-st-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, c-ONB-P(OEGMA-st-DMAEMA) shows a light-cleavable mainchain and pH-sensitive side chains. Notably, doxorubicin (DOX)-loaded c-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.

Macromolecular architectural effects on solution self-assembly of amphiphilic AB-type block copolymers

“…10). 168 These groundbreaking developments underscore the untapped ability and versatility of cyclic polymers in advanced drug delivery technologies, providing opportunities for improved therapeutic strategies in cancer treatment.…”

Loop to linear: exploring the impact of corona topology on the properties of self-assembled polymer nanoparticles

“…Among many stimuli-responsive systems, light has been rediscovered as a favourable stimulus due to its convenience and controllability. 2,8–11 Unlike other stimuli, light offers the advantage of being readily accessible and can be employed without additional reagents and under mild reaction conditions. Various light-responsive systems, such as anthracene dimerisation, 12,13 azobenzene, 11,14 and o -nitrobenzyl ( o -NB), 15–18 have been developed, enabling precise control over molecules by adjusting parameters such as light intensity, wavelength, and irradiation time.…”

A Facile Synthetic Approach to UV-Degradable Hydrogels

“…Numerous studies have shown that the degradation of hydrogels is mainly dependent on the light cleavage groups on the gel polymer chain segments. One of the most common light-cleavable groups is o -nitrobenzyl ester [ 19 , 20 , 21 , 22 , 23 , 24 ], which can absorb UV light energy and use it for the internal chemical reaction to break the chemical bond. The incorporation of light cleavable groups brings a variety of changes to the properties of hydrogels, yet it also imparts certain complexities to their synthesis.…”