Cellulose nanocrystal-annealed hydrogel system for local chemo-metabolic therapy of melanoma

Da In Jeong; Qiaojun Hao; Song Yi Lee; Sungyun Kim; Mrinmoy Karmakar; Seongnam Chu; Miso Park; Hyun-Jong Cho

doi:10.1016/j.jconrel.2024.11.015

Cellulose nanocrystal-annealed hydrogel system for local chemo-metabolic therapy of melanoma

J Control Release. 2024 Nov 11:S0168-3659(24)00760-0. doi: 10.1016/j.jconrel.2024.11.015. Online ahead of print.

Authors

Da In Jeong¹, Qiaojun Hao¹, Song Yi Lee², Sungyun Kim¹, Mrinmoy Karmakar¹, Seongnam Chu³, Miso Park¹, Hyun-Jong Cho⁴

Affiliations

¹ Department of Pharmacy, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.
² Department of Pharmacy, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea; Kangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.
³ Department of Pharmacy, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea; Daehwa Pharmaceutical Co., Ltd., Seoul 06699, Republic of Korea.
⁴ Department of Pharmacy, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea. Electronic address: hjcho@kangwon.ac.kr.

PMID: 39536973
DOI: 10.1016/j.jconrel.2024.11.015

Abstract

A cellulose nanocrystal (CNC)-annealed hydrogel (CAH) structure, including doxorubicin (DOX) and 2-deoxy-d-glucose (2DG), was developed for local chemo-metabolic therapy (LCMT) of melanoma. DOX has been used as a chemotherapeutic agent because of its intercalation into DNA and generation of free radicals. 2DG has been used as a glycolytic inhibitor in multiple metabolic therapies in combination with DOX. Covalent and non-covalent (i.e., ionic and hydrogen-bonding) binding approaches between CNC and drug cargo (i.e., DOX and 2DG) were used to tune the rheological properties of the CAH structure to achieve sustained drug release. Reduction of reduced nicotinamide adenine dinucleotide phosphate, adenosine triphosphate, and mitochondrial membrane potential, and elevation of cellular reactive oxygen species and cleaved caspases 3 and 7 were observed following treatment with CNC/DOX/2DG in B16F10 cells. Glutathione depletion, enhanced lipid peroxidation, and decreased lactate levels were observed in the CNC/DOX/2DG group. After intratumoral injection of the CNC/DOX/2DG hydrogel into B16F10 tumor-bearing mice, stronger tumor growth suppression and anti-recurrence capabilities were observed. These findings imply that the viscoelastically modulated CAH hydrogel system can be a strong candidate for LCMT of melanoma.

Keywords: Chemo-metabolic therapy; Hydrogel; Local injection; Melanoma; Nanocellulose annealing.