Therapeutic cancer vaccines that harness the immune system to reject cancer cells have shown great promise for cancer treatment. Although a wave of efforts have spurred to improve the therapeutic effect, unfavorable immunization microenvironment along with a complicated preparation process and frequent vaccinations substantially compromise the performance. Here, we report a novel microcapsule-based formulation for high-performance cancer vaccinations. The special self-healing feature provides a mild and efficient paradigm for antigen microencapsulation. After vaccination, these microcapsules create a favorable immunization microenvironment in situ, wherein antigen release kinetics, recruited cell behavior, and acid surrounding work in a synergetic manner. In this case, we can effectively increase the antigen utilization, improve the antigen presentation, and activate antigen presenting cells. As a result, effective T cell response, potent tumor inhibition, antimetastatic effects, and prevention of postsurgical recurrence are achieved with various types of antigens, while neoantigen was encapsuled and evaluated in different tumor models.
A method is herein proposed to produce biodegradable microcapsules by a self-healing of porous microspheres, which were prepared from water-in-oil-in-water (W 1 /O/ W 2 ) double-emulsion templates. Methoxypoly(ethylene glycol)-b-poly-DL-lactide (PELA) was dissolved in ethyl acetate (EA) as the oil phase (O) of double emulsion, NaCl and poly(vinyl acetate) aqueous solutions serving as internal and external water phases (W 1 and W 2 ), respectively. Porous PELA microspheres were prepared by a two-step emulsification and solvent extraction method. Core materials, such as proteins or latex particles, could then be loaded by diffusion from the external water phase. Eventually, the pores in the surface could heal up triggered by a solvent swelling or infrared irradiation to form closed microcapsules. Compared with traditional encapsulations which are based on the two-step emulsification, the proposed posthealing approach could overcome some drawbacks, such as the shear destruction, solvent erosion to delicate core materials, or even their unexpected release during the emulsification. Besides PELA, poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) microcapsules were also proved feasible to fulfill such an approach.
With their hierarchical structures and the substantial surface areas, hollow particles have gained immense research interest in biomedical applications. For scalable fabrications, emulsion-based approaches have emerged as facile and versatile strategies. Here, the recent achievements in this field are unfolded via an "emulsion particulate strategy," which addresses the inherent relationship between the process control and the bioactive structures. As such, the interior architectures are manipulated by harnessing the intermediate state during the emulsion revolution (intrinsic strategy), whereas the external structures are dictated by tailoring the building blocks and solidification procedures of the Pickering emulsion (extrinsic strategy). Through integration of the intrinsic and extrinsic emulsion particulate strategy, multifunctional hollow particles demonstrate marked momentum for label-free multiplex detections, stimuli-responsive therapies, and stem cell therapies.
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