Development of injectable in situ hydrogels based on hyaluronic acid via Diels-Alder reaction for their antitumor activities studies.

Autor: Shi Y; College of pharmacy, Xinxiang Medical University, 453003 Xinxiang, PR China. Electronic address: shiyongli2005@163.com., Xu S; College of pharmacy, Xinxiang Medical University, 453003 Xinxiang, PR China., Zhao J; College of pharmacy, Xinxiang Medical University, 453003 Xinxiang, PR China., Zhu H; College of pharmacy, Xinxiang Medical University, 453003 Xinxiang, PR China., Pan X; College of pharmacy, Xinxiang Medical University, 453003 Xinxiang, PR China., Zhao B; Basic Medicine College, Xinxiang Medical University, 453003, Xinxiang, PR China., Sun Z; First Clinical College, Xinxiang Medical University, 453003 Xinxiang, PR China., Li N; College of pharmacy, Xinxiang Medical University, 453003 Xinxiang, PR China. Electronic address: jianjinshuln@163.com., Hou X; College of pharmacy, Xinxiang Medical University, 453003 Xinxiang, PR China; Pingyuan Laboratory, Xinxiang, Henan 453007, PR China. Electronic address: houxueyan1234@yeah.net.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Mar; Vol. 262 (Pt 1), pp. 129642. Date of Electronic Publication: 2024 Jan 23.
DOI: 10.1016/j.ijbiomac.2024.129642
Abstrakt: The objective of this study was to develop an injectable hydrogel based on furfuryl amine-conjugated hyaluronic acid (FA-conj-HA) and evaluate the in vivo anti-4 T1 tumor activity of doxorubicin-loaded hydrogel (DOX@FA-conj-HA gel ). The cargo-free hydrogel (FA-conj-HA gel ) was fabricated through a Diels-Alder reaction at 37 °C with FA-conj-HA as a gel material and four armed poly(ethylene glycol)2000-maleimide (4-arm-PEG2000-Mal) as a cross-linker. The bio-safety of FA-conj-HA gel were assessed, and the in vivo antitumor activity of DOX@FA-conj-HA gel was also investigated. Many 3D network structures were observed from scanning electron microscope (SEM) photograph, confirming the successful preparation of FA-conj-HA gel . The absence of cytotoxicity from FA-conj-HA gel was proved by the high viability of 4 T1 cells. In vivo bio-safety studies suggested that the obtained FA-conj-HA gel did not induce acute toxicity or other lesions in treated mice, confirming its high bio-safety. The reduced tumor volumes, hematoxylin-eosin staining (H&E), and TdT-mediated dUTP-biotin nick end labeling (TUNEL) analysis indicated the potent in vivo anti-4 T1 tumor effects of DOX@FA-conj-HA gel . In conclusion, the favorable bio-safety and potent antitumor activity of DOX@FA-conj-HA gel highlighted its potential application in oncological therapy.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this study.
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Databáze: MEDLINE