Issue 23, 2022

Drug delivery with a pH-sensitive star-like dextran-graft polyacrylamide copolymer

Abstract

The development of precision cancer medicine relies on novel formulation strategies for targeted drug delivery to increase the therapeutic outcome. Biocompatible polymer nanoparticles, namely dextran-graft-polyacrylamide (D-g-PAA) copolymers, represent one of the innovative non-invasive approaches for drug delivery applications in cancer therapy. In this study, the star-like D-g-PAA copolymer in anionic form (D-g-PAAan) was developed for pH-triggered targeted drug delivery of the common chemotherapeutic drugs – doxorubicin (Dox) and cisplatin (Cis). The initial D-g-PAA copolymer was synthesized by the radical graft polymerization method, and then alkaline-hydrolyzed to get this polymer in anionic form for further use for drug encapsulation. The acidification of the buffer promoted the release of loaded drugs. D-g-PAAan nanoparticles increased the toxic potential of the drugs against human and mouse lung carcinoma cells (A549 and LLC), but not against normal human lung cells (HEL299). The drug-loaded D-g-PAAan-nanoparticles promoted further oxidative stress and apoptosis induction in LLC cells. D-g-PAAan-nanoparticles improved Dox accumulation and drugs’ toxicity in a 3D LLC multi-cellular spheroid model. The data obtained indicate that the strategy of chemotherapeutic drug encapsulation within the branched D-g-PAAan nanoparticle allows not only to realize pH-triggered drug release but also to potentiate its cytotoxic, prooxidant and proapoptotic effects against lung carcinoma cells.

Graphical abstract: Drug delivery with a pH-sensitive star-like dextran-graft polyacrylamide copolymer

Article information

Article type
Paper
Submitted
04 มิ.ย. 2565
Accepted
29 ก.ย. 2565
First published
10 ต.ค. 2565
This article is Open Access
Creative Commons BY license

Nanoscale Adv., 2022,4, 5077-5088

Drug delivery with a pH-sensitive star-like dextran-graft polyacrylamide copolymer

A. Grebinyk, S. Prylutska, S. Grebinyk, S. Ponomarenko, P. Virych, V. Chumachenko, N. Kutsevol, Y. Prylutskyy, U. Ritter and M. Frohme, Nanoscale Adv., 2022, 4, 5077 DOI: 10.1039/D2NA00353H

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