MemHsp70 Receptor-mediated Multifunctional Ordered Mesoporous Carbon Nanospheres for Photoacoustic Imaging-Guided Synergistic Targeting Trimodal Therapy

Integrating multiple discrete function-related theranostic modalities into one platform for effective cancer treatments has been considered to be a challenge for current nanomedicine design. In this work, a "four-in-one" theranostic system was simply prepared and developed for photoacoustic (PA) imaging-guided synergistic targeting chemo-gene-thermo trimodal therapy of breast cancer. In this system, polyethylene glycol (PEG)-bridged polyethylenimine (PEI) and a memHsp70 receptor-targeting peptide (TKD), PPT, was uniformly capped on doxorubicin (DOX)-loaded oxidized mesoporous carbon nanospheres (OMCN) to encapsulate therapeutic genes into cancer cells via active targeting accumulation. Taking both the advantages of OMCN (high photothermal conversion, strong PA contrast, and controllable drug loading) and the hydrophilic polymer (gene vector, switchable pores' cap, and targeting ability), the "four-in-one" theranostic system exhibited distinct PA imaging visualization, NIR/pH sensitive drug/gene release, and synergistic targeting therapeutic outcome, which were much superior than the single therapy or the combination of two treatments.