title: Photo- and thermo-responsive multicompartment hydrogels for synergistic delivery of gemcitabine and doxorubicin.
abstract: Hydrogels have found promising applications in drug delivery due to their biocompatibility, high drug loading capability, and tunable release profiles. However, hydrogel-based carriers are primarily employed for delivering hydrophilic payloads while hydrophobic drugs cannot be efficiently delivered due to the lack of hydrophobic domains within conventional hydrogel matrices. Herein, we report that thermo- and photo-responsive hydrogels could be constructed from amphiphilic triblock copolymers, poly(N-isopropylacrylamide)-b-poly(4-acryloylmorpholine)-b-poly(2-((((2-nitrobenzyl)oxy)carbonyl) amino)ethyl methacrylate) (PNIPAM-b-PNAM-b-PNBOC), and the resulting hydrogels could be further engineered a new carrier for both hydrophilic gemcitabine (GCT) and hydrophobic doxorubicin (DOX). PNIPAM-b-PNAM-b-PNBOC triblock copolymers were first self-assembled into micelles with hydrophobic photosensitive PNBOC cores, hydrophilic PNAM inner shells, and thermoresponsive PNIPAM coronas below the lower critical solution temperature (LCST), while hydrogels of physically cross-linked micellar nanoparticles were achieved at elevated polymer concentrations and high temperatures above the critical gelation temperature (CGT). Rheological experiments revealed that the CGT was highly dependent on polymer compositions and concentrations, that is, a longer hydrophobic PNBOC block or a higher polymer concentration led to a decreased CGT. However, the CGT prior to UV irradiation (CGT0) could be drastically elevated after UV irradiation (CGTUV) as a result of UV irradiation-induced concurrently cross-linking and hydrophobic-to-hydrophilic transition within PNBOC cores. As such, gel-to-sol transition could be accomplished by either temperature decrease or exposure to UV irradiation at a fixed temperature lower than the CGTUV. Note that both GCT and DOX could be simultaneously encapsulated into the hydrogels due to the coexistence of extramicellar aqueous phase and hydrophobic micellar cores. Intriguingly, the subsequent co-release of GCT and DOX could be regulated by taking advantage of either temperature or UV irradiation-mediated gel-to-sol transitions.
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, iChem (Collaborative Innovation Center of Chemistry for Energy Materials), Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, iChem (Collaborative Innovation Center of Chemistry for Energy Materials), Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China.
authors.forename: Guoying
authors.initials: G
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, iChem (Collaborative Innovation Center of Chemistry for Energy Materials), Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China. Electronic address: ghliu@ustc.edu.cn.
authors.forename: Guhuan
authors.initials: G
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, iChem (Collaborative Innovation Center of Chemistry for Energy Materials), Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China. Electronic address: jmhu@ustc.edu.cn.
authors.forename: Jinming
authors.initials: J
authors.lastname: Hu
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, iChem (Collaborative Innovation Center of Chemistry for Energy Materials), Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China. Electronic address: sliu@ustc.edu.cn.
authors.forename: Shiyong
authors.initials: S
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000528:radiation effects; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000528:radiation effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000528:radiation effects; D004317:Doxorubicin / Q000737:chemistry / Q000528:radiation effects; D004337:Drug Carriers / Q000737:chemistry / Q000528:radiation effects; D004338:Drug Combinations; D065546:Drug Liberation; D020100:Hydrogels / Q000737:chemistry / Q000528:radiation effects; D008823:Micelles; D011108:Polymers / Q000737:chemistry / Q000528:radiation effects; D013696:Temperature; D014466:Ultraviolet Rays; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004338:Drug Combinations; D020100:Hydrogels; D008823:Micelles; D011108:Polymers; D003841:Deoxycytidine; D004317:Doxorubicin; D000093542:Gemcitabine
keywords: Drug delivery; Hydrogels; Photoresponsive; Sol-gel transition; Thermoresponsive