A metal-coordination stabilized small-molecule nanomedicine with high drug-loading capacity and synergistic photochemotherapy for cancer treatment

Abstract

Conventional nanomedicines typically employ a significant amount of excipients as carriers for therapeutic delivery, resulting in generally low drug-loading and compromised anti-cancer efficacy. Here, we propose a small-molecule nanomedicine (CMC NP) directly assembled using a chemotherapeutic drug (chlorambucil, CBL) and a phototherapeutic agent (chlorin e6, Ce6), and stabilized by metal coordination. The CMC NP exhibits exceptionally high drug loading (89.21%), robust stability, and smart disassembly in response to glutathione (GSH). Such a straightforward yet multifunctional delivery strategy could be a better alternative to overcome the above shortcomings of conventional nanomedicines while achieving enhanced efficacy. The CMC NP not only directly induces CBL-induced chemotherapy but also elicits synergistic antitumor responses through Ce6-mediated photodynamic and photothermal therapies. Owing to the multifaceted efforts from photodynamic, photothermal and chemo-therapies, the CMC NP exhibits excellent antitumor efficacy with negligible systemic toxicity which is untenable in traditional CBL-induced chemotherapy. Therefore, this study provides a feasible strategy for overcoming existing challenges and presents a potential opportunity to augment the clinical therapeutic effectiveness associated with conventional nanomedicine.