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Photoresponsive Zwitterionic Block Copolymer Nanoparticles Prepared by a One-Step Nanoprecipitation–Photocrosslinking Strategy for Precision Cancer Chemotherapy

Authors :

Helia Heydarinasab¹ Vahid Haddadi Asl² Mahdi Tohidian³ Hanie Ahmadi⁴

1- دانشگاه صنعتی امیرکبیر(پلی تکنیک تهران) 2- دانشگاه صنعتی امیرکبیر(پلی تکنیک تهران) 3- دانشگاه صنعتی امیرکبیر(پلی تکنیک تهران) 4- دانشگاه صنعتی امیرکبیر(پلی تکنیک تهران)

Keywords :

zwitterionic copolymer،coumarin methacrylate،RAFT polymerization،nanoprecipitation،photocrosslinking،drug delivery nanoparticles،simultaneous encapsulation

Abstract :

Targeted polymeric nanocarriers are increasingly explored to enhance the efficacy and safety of anticancer therapeutics. In this study, we report the design and fabrication of zwitterionic photoresponsive block copolymer nanoparticles, P(MAA-co-CouMA)-b-PDMAEMA, synthesized via RAFT polymerization. The copolymer combines the non-fouling characteristics of zwitterionic segments with the light-responsive coumarin moieties, enabling photocrosslinking for enhanced structural stability. A one-pot strategy was employed wherein nanoprecipitation, doxorubicin (DOX) encapsulation, and UV-induced crosslinking occurred simultaneously, simplifying fabrication and improving drug-loading efficiency. Characterization by FTIR and ¹H NMR confirmed successful copolymer synthesis, while SEM and DLS analyses revealed spherical nanoparticles with uniform morphology (~150 nm by SEM; ~250 nm hydrodynamic diameter, PDI < 0.2). In vitro DOX release studies at pH 7.4 and 37 °C demonstrated an initial burst release (~10–12%) followed by sustained release (~35% over 50 h), attributed to the coumarin-crosslinked matrix. This integrated approach offers a versatile platform for controlled and targeted drug delivery in cancer therapy.