Indocyanine green–encapsulated nanoscale metal–organic frameworks for highly effective chemo-photothermal combination cancer therapy

Indocyanine green (ICG), as the only U.S. Food and Drug Administration–approved near-infrared (NIR) clinical agent, has been considered as an ideal light absorber for laser-mediated photothermal therapy (PTT) in cancer treatment. However, the practical applications of ICG are severely hampered by its poor aqueous stability, rapid body clearance, and low cellular uptake. To overcome these limitations, we herein report the successful example of integrating ICG into a zeolitic imidazolate framework (ZIF-8) to fabricate a novel nanoscale ICG@ZIF-8 hybrid material . Through a simple one-pot synthesis method, a high loading content of 20.6% can be achieved in the resultant ICG@ZIF-8. The photostability and tumor accumulation of ICG are notably promoted due to the protection of the framework, leading to enhanced photothermal conversion efficiency. Furthermore, we also discover, for the first time, that the pH-triggered release of large amount of Zn 2+ from ZIF-8 in tumor acidic microenvironment also significantly contributes to targeted killing of cancer cells. As a result of the combined PTT and chemotherapy, ICG@ZIF-8 exhibits greatly improved diagnostic efficacy for both in vitro and in vivo cancer therapy, leading to 91% tumor eradication in all the mice treated with ICG@ZIF-8 and NIR irradiation. Hematoxylin and eosin (H&E)–stained slices show that no noticeable tissue damage is observed in major organs, indicating the safety of ICG@ZIF-8.