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ACS Applied Materials & Interfaces

ACS Applied Materials & Interfaces

IF: 8.3
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Tumor-Targeted Metal–Organic Framework for Improved Photodynamic Therapy and Inhibited Tumor Metastasis in Melanoma

Published:9 December 2024 DOI: 10.1021/acsami.4c18058
Wenhao Gao, Yutong Song, Fei Wu, Shiting Xu, Bin Liu, Lingjun Zeng, Enqin Zheng, Hongtao Song, Qian Zhang

Abstract

Tumor hypoxia and elevated intracellular glutathione (GSH) levels significantly compromise the effectiveness of photodynamic therapy (PDT) in treating melanoma. In this study, we synthesized positively charged nanoparticles through a self-assembly method, incorporating photosensitizer verteporfin (VER), mitochondrial respiratory inhibitor atovaquone (ATO), and Fe3+. Subsequently, the nanoparticles were modified with sodium hyaluronate (HA) to obtain HA-ATO-Fe3+-VER nanoparticles (HAFV NPs). The fabricated HAFV NPs demonstrated excellent stability and in vitro Fenton reaction activity. HA facilitated the cellular internalization of HAFV NPs by targeting CD44 receptors, hence relieving tumor hypoxia through the disruption of the mitochondrial respiratory chain and involvement in the Fenton reaction. Simultaneously, ATO directly impeded the biosynthesis of GSH by diminishing ATP levels, while Fe3+ was supposed to oxidate GSH to GSSG, thereby doubly depleting GSH. The integration of these multiple mechanisms markedly enhanced the PDT efficacy of VER. Following intravenous administration, HAFV NPs preferentially accumulated in tumor tissues with minimal accumulation in the skin, demonstrating favorable biocompatibility in vivo. Furthermore, HAFV NPs effectively inhibited tumor growth and lung metastasis, which presents a promising strategy for melanoma treatment.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Coenzyme Q10 303-98-0 C59H90O4 1104 suppliers $10.00-$2850.00
o-Phenylenediamine 95-54-5 C6H8N2 611 suppliers $9.00-$1896.50
Thiazolyl Blue 298-93-1 C18H16N5S.Br 607 suppliers $7.00-$5262.50
FETUIN 9014-81-7 NULL 92 suppliers $37.07-$4810.00

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