Multifunctional cisplatin-loaded polydopamine/MnO2 nanomedicine circumvents drug resistant tumor microenvironment for enhanced chemo-photothermal therapy.

Based on nanomedicine, tumor microenvironment modulation and combination therapy has become an important approach for efficient tumor treatment. Herein, we designed a multifunctional nanoparticle through layer-by-layer strategy. Dopamine self-polymerization forms cisplatin (CDDP) prodrugs encapsulated polydopamine (PDA) core, with a manganese dioxide (MnO2) shell formed on the surface through in situ coating. Targeting molecule hyaluronic acid (HA) is assembled on the surface through electrostatic and coordination interactions, constituting the nanomedicine HMPP NPs. After targeted internalization by tumor cells, MnO2 catalyzes the decomposition of intracellular hydrogen peroxide (H2O2) to generate oxygen (O2). Meanwhile, MnO2 and CDDP prodrug deplete the intracellular glutathione (GSH) to prevent the detoxification effect to CDDP. Therefore, at the first stage HMPP NPs could circumvent the CDDP resistant tumor microenvironment by alleviating tumor hypoxia and GSH depletion. Subsequently, HMPP NPs exert photoacoustic (PA) imaging guided combinational chemo-phototherapy, leveraging the exceptional photothermal properties of PDA. Ultimately, HMPP NPs-mediated combination therapy demonstrates efficient killing of cancer cells in vitro and achieves significant tumor suppression effects in vivo. All in all, this work underscores the importance of nanomedicine mediated tumor microenvironment modulation and combination therapy in combating drug resistance for effective tumor treatment.