Synergistic photothermal/photodynamic suppression of prostatic carcinoma by targeted biodegradable MnO₂ nanosheets

Abstract

The biodegradability and clearance of metal-based nanomaterials have been questioned worldwide, which have greatly limited their clinical translation. Herein, ultrathin manganese dioxide (MnO₂) nanosheets with broad near-infrared (NIR) absorption and pH-dependent degradation properties were prepared. After being modified with polyethylene glycol-cyclic arginine-glycineaspartic acid tripeptide (PEG-cRGD), the MnO₂ nanosheets were then used as photothermal agent and nanocarrier to encapsulate chlorin e6 (Ce6) for targeted photothermal (PTT) and photodynamic (PDT) of cancer. As expected, the MnO₂-PEG-cRGD nanosheets show high Ce6 loading capacity (351 mg/g), superb photothermal conversion performance (37.2%) and excellent colloidal stability. These nanosheets also exhibit pH-dependent and NIR-induced Ce6 release. Furthermore, the MnO₂ nanosheets can be degraded by reacting with hydrogen peroxide in the acidic microenvironment, which are able to elevate the oxygen concentration <i>in situ</i> and thus reverses the tumor hypoxia. Thanks to these favorable properties and the cRGD-mediated tumor-targeted ability, the fabricated MnO₂-PEG-cRGD/Ce6 nanocomposites can be effectively up taken by alpha-v beta-3 (α_vβ₃) integrin over-expressed prostatic carcinoma PC3 cells and achieve favorable therapeutic outcomes under a single 660 nm NIR laser, which is also verified by <i>in vitro</i> studies. The biodegradable MnO₂-PEG-cRGD/Ce6 nanosheets developed in this work can be a promising nanoplatform for synergetic PTT/PDT cancer therapy.