Near-Infrared Cyanine-Loaded Liposome-like Nanocapsules of Camptothecin–Floxuridine Conjugate for Enhanced Chemophotothermal Combination Cancer Therapy

A dual-in-dual synergistic strategy was proposed based on the self-assembly of combinatorial nanocapsules (NCs) from Janus camptothecin-floxuridine (CF) conjugate and the near-infrared absorber of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR) by introducing PEGylated phospholipid of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycerol)-2000] to increase the blood circulation time of NCs. Due to the use of amphiphilic CF and DiR themselves to form liposome-like nanocapsules, the obtained CF-DiR NCs owned a significantly high loading content, a stable co-delivery drug combinations, a no premature release, and an excellent photothermal conversion efficiency. The in vivo fluorescence imaging indicated that CF-DiR NCs could achieve a high tumor accumulation after an intravenous injection. The dual drugs of camptothecin and floxuridine could be coordinately released due to the hydrolysis of the ester bond by the esterase in tumor. The in vivo experiments showed that more cytotoxicity of the CF-DiR NCs-mediated chemo- and photothermal dual therapy to tumor cells could be clearly observed than the chemotherapy or photothermal therapy alone due to the synergistic effect, leading to no recurrence in the entire treatment. All of the results highlighted that CF-DiR NCs were highly effective theranostic agents that could be used for imaging-guided cancer chemophotothermal therapy to conquer an intrinsic resistance to chemotherapeutics.