Multifunctional and multimodality theranostic nanomedicine for enhanced phototherapy

Photodynamic therapy (PDT) has attracted much attention in recent years for its favorable therapeutic efficacy in cancer therapy. However, PDT alone is insufficient to improve the therapeutic efficiency mainly due to the limited penetration depth of light, the insufficient O₂ supply in the hypoxic microenvironment, and the high level of reducing substances in cancer cells. To overcome these limitations, a multifunctional MnO₂ nanoparticle was constructed with honeycomb MnO₂ which was loaded with the photosensitizer Ce6 and modified with polydopamine on its surface (HMnO₂/C&P) to achieve efficient PDT/mild photothermal treatment (PTT) combination therapy. HMnO₂/C&P had high drug loading contents (11.2% Ce6) and can be responsive to the tumor microenvironment (TME), supply O₂ to alleviate the hypoxic microenvironment, and clear GSH to reduce the consumption of ROS, thus enhancing the PDT effect. The introduction of PDA can improve the stability of HMnO₂/C&P, and further give the ability of PTT to act as nanomedicine. The results of in vitro and in vivo experiments show that HMnO₂/C&P based PDT/mild PTT combination therapy has an excellent inhibitory effect on tumor growth. Meanwhile, HMnO₂/C&P can act as a fluorescence imaging reagent and a TME triggerable magnetic resonance imaging (MRI) contrast agent, thus having excellent multimodal self-tracking abilities. Collectively, this study provides a new perspective on the design of multifunctional theranostic nanomedicine to maximize the efficacy of cancer phototherapy.