Targeted delivery of hybrid nanovesicles for enhanced brain penetration to achieve synergistic therapy of glioma.

Blood-brain barrier (BBB) obstructing brain drug delivery severely hampers the therapeutic efficacy towards glioma. An efficient brain delivery strategy is of paramount importance for the treatment of glioma. Inspired by brain targeting exosome, biomimetic BBB penetrated hybrid (pHybrid) nanovesicles, engineered by membrane fusion between blood exosome and tLyp-1 peptide modified liposome, is explored for brain targeting drug delivery. Transferrin receptor (TfR) on pHybrid nanovesicles facilitates the BBB transcytosis into brain parenchyma, and eventually endocytosed by glioma cells and diffusion to extra-vascular tumor tissues under the guidance of tLyp-1 peptide. pHybrid nanovesicles co-loaded with salvianolic acid B (SAB) and cryptotanshinone (CPT), which is constructed by membrane hybridization of blood exosome loaded with SAB and tLyp-1 modified liposome loaded with CPT, are explored for cytotoxic and anti-angiogenetic therapy towards glioma. Upon accumulation at tumor site, the loaded CPT and SAB shows synergistic effects towards glioma from cytotoxicity on cancer cells and anti-angiogenesis on tumor, respectively. Overall, this study provides a biomimetic nanoplatform for increased BBB transcytosis into brain parenchyma, which serves as a prospective strategy for delivering therapeutic agents against glioma through synergistic mechanisms.

Gather wisdom to overcome barriers: Well-designed nano-drug delivery systems for treating gliomas.

Due to the special physiological and pathological characteristics of gliomas, most therapeutic drugs are prevented from entering the brain. To improve the poor prognosis of existing therapies, researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy. Although these strategies can be used clinically to overcome the blood‒brain barrier (BBB), the accurate delivery of drugs to the glioma lesions cannot be ensured. Nano-drug delivery systems (NDDS) have been widely used for precise drug delivery. In recent years, researchers have gathered their wisdom to overcome barriers, so many well-designed NDDS have performed prominently in preclinical studies. These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions, drug release in response to the glioma microenvironment, biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein, and carriers created according to the active ingredients of traditional Chinese medicines. We reviewed these well-designed NDDS in detail. Furthermore, we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy, and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.

Tumor-derived extracellular vesicles as messengers of natural products in cancer treatment.

Extracellular vesicles (EVs) are kinds of two-layer vesicles secreted by cells. They play significant roles in mediating component exchange between cells, signal transduction, and pathological development. Among them, the tumor-derived EVs (TDEVs) are found related to the tumor microenvironment and cancer development. TDEVs can be designed as a natural drug carrier with high tumor targeting and permeability. In recent years, drug delivery systems (DDS) based on TDEVs for cancer treatments have received considerable attention. In this review, the biological characteristics of TDEVs are introduced, especially the effect on the tumor. Furthermore, the various approaches to constructing DDS based on TDEVs are summarized. Then we listed examples of TDEVs successfully constructing treatment systems. The use of chemical drugs, biological drugs, and engineered drugs as encapsulated drugs are respectively introduced, particularly the application progress of active ingredients in traditional Chinese medicine. Finally, this article introduces the latest clinical research progress, especially the marketed preparations and challenges of clinical application of TDEVs.