TY - JOUR A1 - Grebinyk, Anna A1 - Prylutska, Svitlana A1 - Grebinyk, Sergii A1 - Ponomarenko, Stanislav A1 - Virych, Pavlo A1 - Chumachenko, Vasyl A1 - Kutsevol, Nataliya A1 - Prylutskyy, Yuriy A1 - Ritter, Uwe A1 - Frohme, Marcus T1 - Drug delivery with a pH-sensitive star-like dextran-graft polyacrylamide copolymer TI - Nanoscale Advances N2 - 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. Y1 - 2022 UR - https://opus4.kobv.de/opus4-th-wildau/frontdoor/index/index/docId/1674 UR - https://nbn-resolving.org/urn:nbn:de:kobv:526-opus4-16749 VL - 4 IS - 23 SP - 5077 EP - 5088 PB - Royal Society of Chemistry (RSC) ER -