Peptide–Drug Conjugate-Based Nanocombination Actualizes Breast Cancer Treatment by Maytansinoid and Photothermia with the Assistance of Fluorescent and Photoacoustic Images

To develop a highly efficient strategy against tumors, here, a nanocombination (PDC/P@HCuS) was designed and constructed to actualize chemo-phototherapy with the assistance of fluorescence (FL) and photoacoustic (PA) images. First, a type of organic-inorganic hybrid nanosystem (P@HCuS) was engineered by coupling the fluorescence-labeled amphiphilic fPEDC copolymer on the surface of hollow mesoporous copper sulfide nanoparticle (HCuS), in which HCuS was used as a photothermal and PA agent; fPEDC as a stabilizer, chromophore, and redox/pH-sensitive gatekeeper; and both of them as drug carriers. Then, a peptide-drug conjugate (cRGD-SMCC-DM1, PDC), as a molecular targeted maytansinoid, was loaded inside of P@HCuS to form PDC/P@HCuS. Next, the PDC/P@HCuS was investigated carefully with or without near-infrared (NIR) laser irradiation. In vitro, the nanocombination exhibited stimuli-responsive drug release, obvious cellular uptake, strong cytotoxicity to tumor cells, significant impact on cell cycle, and cytoskeleton and cellular proteomics as well as evident permeability into the tumor sphere, most of which could be boosted by NIR laser irradiation. In vivo, the nanocombinaiton exerted good FL/PA imaging features and photothermal efficiency, achieved the best antitumor efficacy in the presence of NIR laser irradiation, and showed excellent biosafety. Together, it demonstrated that the PDC/P@HCuS, representing a chemo-phototherapy based on a nanocombination associated with peptide-drug conjugate, could achieve the highly efficient antitumor effect.