Abstract

AbstractAs a typical characteristic of solid tumors, hypoxia diminishes the efficiency of oxygen‐dependent cancer therapy, such as type II photodynamic therapy (PDT). Tumor‐targeted multifunctional nanomedicine that overcomes hypoxic resistance is therefore highly desirable. The authors present an efficient strategy against hypoxic tumors based on aptamer‐targeting and 808 nm laser‐triggered three phototherapeutic pathways, which uses a hybrid with carbon dots, IR820 dye, and anti‐vascular endothelial growth factor aptamer as a novel nanomedicine (CD‐IR820‐Aptamer) with simultaneous type I PDT (PDT I), type II PDT (PDT II), and photothermal therapy (PTT) under single 808 nm laser irradiation. The obtained CD‐IR820‐Aptamer exhibits tumor‐targeting and mitochondrial accumulation. Direct phosphorescent spectra and photothermal imaging analyses demonstrates that CD‐IR820‐Aptamer can elicit O2•−, •OH (for PDT I), 1O2 (for PDT II), and heat (for PTT) via three pathways triggered by single 808 nm laser irradiation. The oxygen‐independent production of •OH and heat ensures the applicability of CD‐IR820‐Aptamer under hypoxic conditions. Through three phototherapeutic pathways are simultaneously triggered by 808 nm laser irradiation, the proposed nanohybrid displayed high efficiency for treating solid tumors. This work provides a basis for constructing new types of photoactive nanomedicines with targeting ability and improved therapeutic efficiency under hypoxic conditions that can be further used for cancer therapy in clinical trials.

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