Glioblastoma (GBM) belongs to the deadliest primary malignancies with high mortality rate and poor prognosis. Over the past decades, less progress has been made to treat GBM, owing largely to the lack of effective chemotherapeutics and poor drug accumulation in the glioma tissue. In order to address this issue, we present an efficient biomimetic nanocomposite (Cu2−xSe-CB@MEM, CCM), consisting of Cu2−xSe nanoparticle core modified by cinobufotalin (CB), a toad venom extract, which is camouflaged with glioma cell Ln229 membrane. It is demonstrated that CB can decrease the protein activity of inosine monophosphate dehydrogenase 1 (IMPDH1), a key target correlated with prognosis, through intermolecular hydrogen bonding with amino acid residues ARG-105 and ASP-77. The glioma cell membrane-camouflage endows the CCM with blood-brain barrier penetration and homology tumor-targeted ability. The optimized cinobufotalin based chemotherapy combining with the near-infrared-II (NIR-II) irradiation shows outstanding inhibition effect to glioma cells, by blocking cell cycle and inducing apoptosis. In vivo mice bearing orthotopic Ln229 GBM treated with CCM+NIR-II (CCM+L) have significantly suppressed tumor growth and extended survival, without side effect. The glioma cell membrane camouflaged nanocomposite of Cu2−xSe and cinobufotalin with its significant anti-glioma property and well biosafety will provide novel alternatives for clinical treatment of GBM.
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Bufalin is efficacious in treating various tumors, however, the clinical application of which is restricted by the myocardial toxicity. Developing a smart synergetic delivery system is widely considered as a promising therapeutic strategy. To address this issue, a black phosphorus hybrid polypeptides hydrogel was designed to highly load bufalin, and achieved near-infrared (NIR)-controllable drug release with synergistic photothermal-chemo therapeutic effect. Black phosphorus nanosheets (BPNSs) and bufalin were co-loaded in temperature-sensitive supramolecular hydrogel to receive smart hybridization (BP-bufalin@SH). With NIR irradiation (1 W·cm-2), BP-bufalin@SH exhibited a rapid and large temperature increase and released bufalin via light-controllable manner, with which the side effects of bufalin were greatly decreased. Combined with photothermal-chemo therapeutic effect, BP-bufalin@SH could collapse the mitochondrial transmembrane potential resulting in the irreversible apoptosis of tumor cells, and realize a highly efficient in vivo tumor elimination with good biosafety and biocompatibility. This work provides a new hydrogel platform for controlling bufalin release, and thus further promotes the practical application on antitumor therapy.