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.
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 |