Carboxylesterase-activatable multi-in-one nanoplatform for near-infrared fluorescence imaging guided chemo/photodynamic/sonodynamic therapy toward cervical cancer.

Abstract

Traditional tumor treatment faces great challenge owning to inherent drawbacks. Activatable prodrugs with multi-modality therapeutic capacity are highly desired. In this consideration, a responsiveness-released multi-in-one nanoplatform, PLGA-PEG@HC, toward cervical cancer therapy was innovatively developed. Among the nanoplatform, HC was constructed by incorporating chlorambucil, a classic chemotherapy drug into a near-infrared photo- and sono-sensitizer, HCH via ester linker, which can be specifically hydrolyzed by carboxylesterase (CES). HC is scarcely fluorescent and toxic due to the caging of HCH and chlorambucil, thus achieving low background signal and minimal side effects. However, once selectively hydrolyzed by tumor enriched CES, ester bond will be broken. Consequently, HCH and chlorambucil are released so as to achieve near-infrared fluorescence imaging and synergistic photodynamic/sonodynamic/chemo therapy. PLGA-PEG packaging ensures the biocompatibility of HC. The as-obtained nanoplatform, with diameter of 97 nm, achieves tumor targeting capacity via EPR. In vitro and in vivo applications have demonstrated that PLGA-PEG@HC can accumulate in tumor tissues, exhibit CES-activatable near-infrared fluorescence imaging and efficient tumor suppression capacity. Compared with the reported combinational therapy materials which are complex in compositions, PLGA-PEG@HC is simple in formulation but demonstrates near-infrared fluorescence traced and considerable therapy efficacy toward tumors, which may accelerate the clinical translation.