Nanoarchitectured hyaluronic acid-decorated hierarchical drug-like assemblies as synergistic immune modulators against breast carcinoma.

Considering the challenges of delivering drugs using nanoparticles, fabricating an intelligent drug-like nanocomposite platform with exceptional therapeutic effects has attracted enormous interest in achieving safe and highly effective tumor treatment. Although the activation of materials using external sources (light) is of great importance, it is obligatory to synergistically activate the internal stimuli, such as deadly free radicals and immune responses. This study aims to fabricate conformational biocompatible nanoassemblies based on in-situ grown platinum nanodots (Pt NDs) on the surface of manganese dioxide (MnO2) nanoflowers, followed by hyaluronic acid (HA) encapsulation (shortly HMP), enabling chemodynamic therapy (CDT), photothermal therapy (PTT), photothermal imaging, and immunotherapy synergistically. The HMP nanocomposites with enhanced photothermal conversion efficiency could deplete GSH in the tumor microenvironment, followed by the release of Mn2+ and Pt NDs. Mn2+ could further react with H2O2 to generate hydroxyl radicals (·OH) through a Fenton-like reaction, resulting in the CDT effect. The presence of Pt NDs showed an improvement in the photothermal conversion efficiency of HMP nanoassemblies (35.46 %) towards the PTT effect. In addition to synergistic (CDT and PTT) actions in 4 T1 cells in vitro, low doses of HMP nanocomposites could stimulate the high mobility group box 1 (HMGB-1) release and generate calreticulin (CRT) protein in tumor cells to provide necessary signals for immunotherapeutic destruction. Finally, HMP nanocomposites combined with light stimulation could effectively inhibit tumor growth in BALB/c tumor-bearing mice. In summary, the designed drug-free nanoassemblies resulted in enhanced tumor suppression through synergistic CDT, PTT, and potential immunotherapy therapeutic effects.