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.