In Situ Separable Nanovaccines with Stealthy Bioadhesive Capability for Durable Cancer Immunotherapy.

Because of tumor heterogeneity and the immunosuppressive tumor microenvironment, most cancer vaccines typically do not elicit robust antitumor immunological responses in clinical trials. In this paper, we report findings about a bioadhesive nanoparticle (BNP)-based separable cancer vaccine, FeSHK@B-ovalbumin (OVA), to target multi-epitope antigens and exert effective cancer immunotherapy. After the FeSHK@B-OVA "nanorocket" initiates the "satellite-rocket separation" procedure in the acidic tumor microenvironment, the FeSHK@B "launch vehicle" can amplify intracellular oxidative stress persistently. This procedure allows for bioadhesiveness-mediated prolonged drug retention within the tumor tissue and triggers the immunogenic death of tumor cells that transforms the primary tumors into antigen depots, which acts synergistically with the OVA "satellite" to trigger robust antigen-specific antitumor immunity. The cooperation of these two immunostimulants not only efficiently inhibits the primary tumor growth and provokes durable antigen-specific immune activation in vivo but also activates a long-term and robust immune memory effect to resist tumor rechallenge and metastasis. These results highlight the enormous potential of FeSHK@B-OVA to serve as an excellent therapeutic and prophylactic cancer nanovaccine. By leveraging the antigen depots in situ and the synergistic effect among multi-epitope antigens, such a nanovaccine strategy with stealthy bioadhesion may offer a straightforward and efficient approach to developing various cancer vaccines for different types of tumors.

Bioadhesive Nanoparticles for Local Drug Delivery.

Local drug delivery is an effective strategy for achieving direct and instant therapeutic effects. Current clinical treatments have fallen short and are limited by traditional technologies. Bioadhesive nanoparticles (NPs), however, may be a promising carrier for optimized local drug delivery, offering prolonged drug retention time and steadily maintained therapeutic concentrations. In addition, the possibility of clinical applications of this platform are abundant, as most polymers used for bioadhesion are both biodegradable and biocompatible. This review highlights the major advances in the investigations of polymer-based bioadhesive nanoparticles and their innumerable applications in local drug delivery.

[Comparison of techniques irrigating and reversing rabbit ear vein to digest, isolate and culture endothelial cells].

OBJECTIVE: To establish the better method for isolating and culturing the endothelial cells (ECs). METHODS: The "irrigative digestion" and "reverse interiorly-exteriorly digestion" methods were performed for digesting, isolating, collecting and culturing the ear vein endothelial cells of rabbit. The trypan blue stain was used to test the cell activity. The third-passage cell was identified by factor VI related antigen. The differences between the methods in cell number, activity and purity were compared to get an optimal method. RESULTS: The number of ECs deriving from the "irrigative digestion" method had no significant difference from that deriving from the "reverse interiorly-exteriorly" method when cells were isolated from rabbit ear vein originally. However, after cultured for 5 or 10 days, the vein endothelial cells from the "irrigative digestion" method showed the growth status superior to those from the "reverse interiorly-exteriorly" method. The cultured cells had a cobble stone appearance with a strict monolayer growth, it could be observed under inverted microscope. The factor VIII related antigen was tested by immunohistochemistry, it supported that the cultured cells was ECs. CONCLUSION: The "irrigative digestion" method is the better choice to isolate endothelial cells from small vessel.