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Title: Glycopolymers Mediate Suicide Gene Therapy in ASGPR-Expressing Hepatocellular Carcinoma Cells in Tandem with Docetaxel
Authors: Santo, Daniela 
Cordeiro, Rosemeyre A. 
Mendonça, Patrícia V. 
Serra, Arménio 
Coelho, Jorge 
Faneca, Henrique 
Issue Date: 13-Mar-2023
Publisher: American Chemical Society
Project: This work was financed by the European Regional Development Fund (ERDF) through the COMPETE 2020 program (Operational Program for Competitiveness and Internationalization) and Portuguese national funds via FCT Fundação para a Ciência e a Tecnologia, under projects: IF/01007/2015, POCI-01-0145-FEDER-30916, UIDB/04539/2020, and UIDP/04539/2020. D.S. acknowledges FCT for the Grant: SFRH/BD/132601/2017. R.C. acknowledges financial support from FCT by Scientific Employment Stimulus 2020.00186.CEECIND. The 1H NMR data were collected at the UC-NMR facility which is supported in part by FEDER European Regional Development Fund through the COMPETE Programme (Operational Programme for Competitiveness) and by National Funds through FCT Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) through grants REEQ/481/QUI/2006, RECI/QEQ-QFI/0168/2012, CENTRO-07-CT62-FEDER- 002012, and Rede Nacional de Ressonância Magnética Nuclear (RNRMN). 
Serial title, monograph or event: Biomacromolecules
Volume: 24
Issue: 3
Abstract: Cationic glycopolymers stand out as gene delivery nanosystems due to their inherent biocompatibility and high binding affinity to the asialoglycoprotein receptor (ASGPR), a target receptor overexpressed in hepatocellular carcinoma (HCC) cells. However, their synthesis procedure remains laborious and complex, with problems of solubilization and the need for protection/deprotection steps. Here, a mini-library of well-defined poly(2-aminoethyl methacrylate hydrochloride-co-poly(2-lactobionamidoethyl methacrylate) (PAMA-co-PLAMA) glycopolymers was synthesized by activators regenerated by electron transfer (ARGET) ATRP to develop an efficient gene delivery nanosystem. The glycoplexes generated had suitable physicochemical properties and showed high ASGPR specificity and high transfection efficiency. Moreover, the HSV-TK/GCV suicide gene therapy strategy, mediated by PAMA144-co-PLAMA19-based nanocarriers, resulted in high antitumor activity in 2D and 3D culture models of HCC, which was significantly enhanced by the combination with small amounts of docetaxel. Overall, our results demonstrated the potential of primary-amine polymethacrylate-containing-glycopolymers as HCC-targeted suicide gene delivery nanosystems and highlight the importance of combined strategies for HCC treatment.
ISSN: 1525-7797
DOI: 10.1021/acs.biomac.2c01329
Rights: openAccess
Appears in Collections:FCTUC Eng.Química - Artigos em Revistas Internacionais
IIIUC - Artigos em Revistas Internacionais
I&D CEMMPRE - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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