Polydopamine-coated mesoporous silica nanoparticles for multi-responsive drug delivery and combined chemo-photothermal therapy

Synergistic therapy of chemotherapy and photothermal therapy exhibits great potential to improve the therapeutic efficiency for cancer therapy. In this study, a new biocompatible multiple sensitive drug delivery system (DDS) was synthesized by covering a polydopamine (PDA) layer on doxorubicin (DOX)-loaded mesoporous silica nanoparticle (MSN) via disulfide bonds (MSN-SS-PDA/DOX). PDA worked as a photothermal therapy (PTT) agent and also a gate keeper to control drug release, which was highly sensitive to pH and could prolong the residence time, simultaneously increase water solubility and biocompatibility of the nanoparticles. The DDS exhibited excellent monodispersity, redox/pH/NIR-multi-dependent release characteristics, remarkable photothermal conversion property (photothermal conversion efficiency eta = 40.21%) and outstanding tumor cell synergistic killing efficiency of chemotherapy and photothermal therapy (combination index CI = 0.175). The biodistribution and pharmacodynamics experiments of MSN-SS-PDA/DOX in 4T1 tumor models indicated that MSN-SS-PDA made more DOX accumulate in tumor tissue than free DOX, extend circulation time of DOX in the body, and exhibit a significant synergistic antitumor efficacy. Meanwhile, the tumor growth was remarkably inhibited, which was much more obvious than any monotherapy effect. Thus, the novel nanoplatform presents a promising future as a drug delivery system for combination therapy.