Hederagenin (HED) has poor anticancer activity whose mechanism remains unclear and unsystematic. Free drugs for cancer treatment exhibit disadvantages such as poor targeting and efficacy. To address this problem, we constructed a nanoplatform of black phosphorus quantum dots (BPQDs) camouflaged with a platelet membrane (PLTm) carrying HED, termed PLT@BPQDs-HED. PLTm vesicles serve as a shell to encapsulate multiple high-efficiency drug-loaded nanocores, which can target tumor sites and significantly improve antitumor activity. Compared with free HED, this platform significantly reduced tumor cell viability and the mitochondrial membrane potential (MMP), while increasing the production of intracellular reactive oxygen species (ROS). The platform also significantly increased the amounts of terminal deoxyribonucleotide transferase mediated dUTP nick-end-labeling (TUNEL)-positive cells and decreased the number of Ki-67-positive cells. In addition, the platform upregulated proapoptotic factor Bax, downregulated the anti-apoptotic molecule Bcl-2, activated Caspase-9 and Caspase-3, and stimulated Cytochrome C release. Moreover, the platform promoted the formation of autophagosomes, upregulated Beclin-1, and promoted LC3-I conversion into LC3-II. This study demonstrated that the above platform significantly enhances tumor targeting and promotes mitochondria-mediated cell apoptosis and autophagy in tumor cells.

An eikonal equation-based tomography method is used to invert the high-quality regional and teleseismic traveltime data recorded by 26 broadband seismic stations in northern Sumatra, following which we obtain the P and S wave velocity structures of the crust and mantle down to a depth of 800 km. The results of both P and S wave tomography clearly show that the Indo-Australian oceanic plate continuously penetrates downward beneath northern Sumatra and the maximum penetration depth varies approximately from 400 km at the northern tip of Sumatra to about 800 km around the southern boundary of our study area. Significant slab folding or bending reported in the literature as the main feature of the subducted slab beneath northern Sumatra is not found in our results. Instead, our tomographic images demonstrate only a less curved slab that mimics the shape of the Sunda Trench and volcanic arc and generally extends over depths from 120 to 450 km. P wave tomography shows broad and pronounced low-velocity anomalies beneath the island of Sumatra in the lower crust and uppermost mantle. Our model also reveals a slab tear approximately at 120-km depth, which has been documented in previous studies and considered to be related to the eruption of the Toba supervolcano.

No abstract