With the recent advances in nanomaterials, photothermal therapies (PTT) enabled by deep-tissue penetration with novel nanoagents have offered a new hope for treating cancers. Nevertheless, PTT applications in conventional approaches remain translationally restricted due to their non-specificity and collateral pro-inflammatory effects during implementation. To address these drawbacks, we here report Lipo-PTO as the prototype of a new class of liposome-functionalized photothermal theragnostic agents, which can eradicate cancer cells in vivo with high selectivity. Lipo-PTO is activated by low pH and superoxide (O2•–) to specifically deliver and convert preloaded cyanine molecules to release Cy-NH in the tumour microenvironments, eventually enabling the activation of photothermal properties to induce tumour ablation. In further studies on Lipo-PTO for treating breast cancer (BC) in mouse models, Lipo-PTO usage was characterized by a high degree of biocompatibility, optimal retention time pharmacokinetics and tumour regression with minimal collateral damages. This study here thus illustrates an innovative strategy to target intrinsic attributes of tumour microenvironments for improved therapeutic precision and efficacy in PTT applications.
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