Aptamer and IR820 Dual-Functionalized Carbon Dots for Targeted Cancer Therapy against Hypoxic Tumors Based on an 808 nm Laser-Triggered Three-Pathway Strategy

As 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 O-2(center dot-), (OH)-O-center dot (for PDT I), O-1(2) (for PDT II), and heat (for PTT) via three pathways triggered by single 808 nm laser irradiation. The oxygen-independent production of (OH)-O-center dot 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.