Construction Of High Loading Natural Active Substances Nanoplatform and Application in Synergistic Tumor Therapy.

ABSTRACT

Background: Natural bioactive substances have been widely studied for their superior anti-tumor activity and low toxicity. However, natural bioactive substances suffer from poor water-solubility and poor stability in the physiological environment. Therefore, to overcome the drawbacks of natural bioactive substances in tumor therapy, there is an urgent need for an ideal nanocarrier to achieve high bioactive substance loading with low toxicity. Materials and Methods: Face-centered cubic hollow mesoporous Prussian Blue (HMPB) NPs were prepared by stepwise hydrothermal method. Among them, PVP served as a protective agent and HCl served as an etching agent. Firstly, MPB NPs were obtained by 0.01 M HCl etching. Then, the highly uniform dispersed HMPB NPs were obtained by further etching with 1 M HCl. Results: In this work, we report a pH-responsive therapeutic nanoplatform based on HMPB NPs. Surprisingly, as-prepared HMPB NPs with ultra-high bioactive substances loading capacity of 329 µg mg-1 owing to the large surface area (131.67 m2 g-1) and wide internal pore size distribution (1.8-96.2 nm). Moreover, with the outstanding photothermal conversion efficiency of HMPB NPs (30.13%), natural bioactive substances were released in the tumor microenvironment (TME). HMPB@PC B2 achieved excellent synergistic therapeutic effects of photothermal therapy (PTT) and chemotherapy (CT) in vivo and in vitro without causing any extraneous side effects. Conclusion: A biocompatible HMPB@PC B2 nanoplatform was constructed by simple physical adsorption. The in vitro and in vivo experiment results demonstrated that the synergy of PTT/CT provided excellent therapeutic efficiency for cervical cancer without toxicity. Altogether, as-designed nanomedicines based on natural bioactive substances may be provide a promising strategy for cancer therapy.