Carrier-free chemo-phototherapeutic nanomedicines with endo/lysosomal escape function enhance the therapeutic effect of drug molecules in tumors

Feng, Xue, Brown, Calum M., Wang, Hongdi, Kashif, Saima, Roberts, Sam, Yan, Li, Munshi, Tasnim, Hands, Philip J. W., Zhang, Wenjun and Chen, Xianfeng 2024. Carrier-free chemo-phototherapeutic nanomedicines with endo/lysosomal escape function enhance the therapeutic effect of drug molecules in tumors. Journal of Materials Chemistry B: Materials for biology and medicine 12 (27) , pp. 6703-6715. 10.1039/D4TB00465E

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Abstract

Carrier-free nanomedicines offer advantages of extremely high drug loading capacity (>80%), minimal non-drug constituent burden, and facile preparation processes. Numerous studies have proved that multimodal cancer therapy can enhance chemotherapy efficiency and mitigate multi-drug resistance (MDR) through synergistic therapeutic effects. Upon penetration into the tumor matrix, nanoparticles (NPs) are anticipated to be uptaken by cancer cells, primarily through clathrin-meditated endocytosis pathways, leading to their accumulation in endosomes/lysosomes within cells. However, endo/lysosomes exhibit a highly degradative environment for organic NPs and drug molecules, often resulting in treatment failure. Hence, this study designed a lysosomal escape mechanism with carrier-free nanomedicine, combining the chemotherapeutic drug, curcumin (Cur), and the photothermal/photodynamic therapeutic drug, indocyanine green (ICG), for synergistic cancer treatment (ICG-Cur NPs) via a facile preparation process. To facilitate endo/lysosomal escape, ICG-Cur NPs were modified with metal-phenolic networks (MPNs) of different thickness. The results indicate that a thick MPN coating promotes rapid endo/lysosomal escape of ICG-Cur NPs within 4 h and enhances the photothermal conversion efficiency of ICG-Cur NPs by 55.8%, significantly improving anticancer efficacy in both chemo- and photo-therapies within 3D solid tumor models. This finding underscores the critical role of endo/lysosomal escape capacity in carrier-free drug NPs for therapeutic outcomes and offers a facile solution to achieve it.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Engineering
Publisher:	Royal Society of Chemistry
ISSN:	2050-7518
Date of Acceptance:	11 June 2024
Last Modified:	28 Feb 2025 15:00
URI:	https://orca.cardiff.ac.uk/id/eprint/176442

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