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

  • 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.

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Metadaten
Author:Anna GrebinykORCiD, Svitlana PrylutskaORCiD, Sergii GrebinykORCiD, Stanislav Ponomarenko, Pavlo Virych, Vasyl Chumachenko, Nataliya KutsevolORCiD, Yuriy PrylutskyyORCiD, Uwe RitterORCiD, Marcus FrohmeORCiDGND
URN:urn:nbn:de:kobv:526-opus4-16749
DOI (Version of Record):https://doi.org/10.1039/D2NA00353H
Parent Title (English):Nanoscale Advances
Publisher:Royal Society of Chemistry (RSC)
Document Type:Article
Language:English
Year of Publication:2022
Publishing Institution:Technische Hochschule Wildau
Release Date:2022/11/25
Volume:4
Issue:23
First Page:5077
Last Page:5088
Source:Grebinyk, A., Prylutska, S., Grebinyk, S., Ponomarenko, S., Virych, P., Chumachenko, V., … Frohme, M. (Eds.). (2022). Drug delivery with a pH-sensitive star-like dextran-graft polyacrylamide copolymer. Nanoscale Advances, 4(23), 5077–5088.
Faculties an central facilities:Fachbereich Ingenieur- und Naturwissenschaften
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Funding:Publikationsfonds der TH Wildau
Licence (German):Creative Commons - CC BY 3.0 - Namensnennung 3.0 Unported
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