Biomimetic Diselenide-Bridged Mesoporous Organosilica Nanoparticles as an X-ray-Responsive Biodegradable Carrier for Chemo-Immunotherapy.

Chemotherapy causes off-target toxicity and is often ineffective against solid tumors. Targeted and on-demand release of chemotherapeutics remains a challenge. Here, cancer-cell-membrane-coated mesoporous organosilica nanoparticles (MONs) containing X-ray- and reactive oxygen species (ROS)-responsive diselenide bonds for controlled release of doxorubicin (DOX) at tumor sites are developed. DOX-loaded MONs coated with 4T1 breast cancer cell membranes (CM@MON@DOX) show greater accumulation at tumor sites and prolonged blood circulation time versus an uncoated control in mice bearing 4T1 orthotopic mammary tumors. Under low-dose X-ray radiation, the DOX-loaded MONs exhibit carrier degradation-controlled release via cleavage of diselenide bonds, resulting in DOX-mediated immunogenic cell death at the tumor site. Combination with a PD-L1 checkpoint blockade further enhances inhibition of tumor growth and metastasis with low systemic toxicity. Together, the findings show the promise of these biomimetic, radiation-responsive diselenide-bond-bridged MONs in chemo-immunotherapy.

Directed Graphene-Based Nanoplatforms for Hyperthermia: Overcoming Multiple Drug Resistance.

Multidrug resistance (MDR), which leads tumors resistance to traditional anticancer drugs, can cause the failure of chemotherapy treatments. Herein, we present a new way to overcome this problem using smart multifunctional graphene-based drug delivery systems which can target subcellular organelles and show synergistic hyperthermia and chemotherapy. Mitochondria-targeting ligands are conjugated onto the doxorubicin-loaded, polyglycerol-covered nanographene sheets to actively accumulate them inside the mitochondria after charge-mediated cellular internalization. Upon near-infrared (NIR) irradiation, adenosine triphosphate (ATP) synthesis and mitochondrial function were inhibited and doxorubicin released into the cellular interior. The hyperthermia-accelerated drug release led to a highly selective anticancer efficiency, confirmed by in vitro and in vivo experiments.