pH/near-infrared light dual activated Ce6-doped silicon nanoparticles with tumor chemo-photodynamic synergistic therapy for improving efficiency of monotherapy

Currently, single chemotherapeutics or photosensitizers implemented in clinic present huge challenges in terms of unfavorable therapeutic efficacy, physiological instability and non-selective toxicity. In order to remedy the faultiness of insufficient efficiency of monotherapy, we herein synthesized an “all-in-one” targeting drug delivery system with multimodal therapy based on chemo-photodynamic synergistic therapy. Specifically, mesoporous silica nanorods were first synthesized through doping chlorin e6 (Ce6) in the sol–gel process, and then were used to load chemotherapy drug. After the amino groups and boronic acid groups were sequentially modified on the surface of nanoparticles, lactobionic acid (LA) was chosen as an intermediary to achieve simultaneous crosslinking of targeting agent LA and sealing agent sericin through pH responsive boronic ester linkage. The obtained ultimate nanocomposites possessed good biocompatibility, colloidal stability and hemocompatibility. Besides, in vitro endocytosis experiment performed with confocal laser scanning microscopy and flow cytometry testified the LA-mediated accurate tumor-specific targeting ability of synthesized nanocarriers. Moreover, a series of in vitro assays demonstrated that fabricated therapeutic nanoplatform could not only release loaded drugs in response to acidic environment to achieve chemotherapy, but also could generate singlet oxygen from photosensitizer Ce6 under external light stimulation to realize photodynamic therapy. Most interestingly, the combination therapy including photodynamic therapy and chemotherapy exhibited a synergistic effect against tumor cells in both in vivo and ex vivo experiments. Briefly, the drug delivery system reported here could attain effective chemo-photodynamic synergistic therapy to dispose of the insufficient lethality of monotherapy while guaranteeing the safety during in vivo application.