Rational design of vaccine adjuvants may provide protective immunity against infective diseases through immune-stimulation.DCs (Dentritic cells) are the most prominent APCs (antigen-presenting cells).In view of the potential use of targeting antigens to the DCs, particulate delivery systems, especially microparticles, have received considerable interest for application in antigen delivery.Antigen release behaviors play a pivotal role in antigen delivery.After uptake by DCs, microparticles containing antigens get into the endosome/lysosome.If antigens slowly release from microparticles, they will co-localized with endosome/lysosome, then be processed and bounded with MHCⅡ molecules and mainly induce humoral response.While, if antigens release from microparticles rapidly, they may escape into the cytoplasm, then be processed and bounded with MHCI molecules, finally generate CTL (cytotoxic T lymphocyte) responses which play an important role in virus infections.In order to achieve these strong immune response described above, we design a novel PLGA microparticles with big cavity structure which co-encapsulate the "antigen chaperons" (specific inorganics).These "antigen chaperons" can react with hydrogen ions in the endosome/lysosome of DCs (pH~ 5.0 and 6.5) to generate gas, which assists antigens release fast and escape into the cytoplasm to induce strong immunology reaction.We have successfully prepared the novel PLGA microparticles with narrow size distributions by SPG membrane emulsification, and their averge size was 1000 nm.The results of SEM and TEM showed that these designed microparticles had thinner shell and bigger inner cavity comparing with the conventional ones.The XRD diffraction pattern of the designed microparticles containing "antigen chaperons" combined those XRD diffraction patterns of empty microparticles and free "antigen chaperons", revealing that those inorgaincs were successfully encapsulated in the particles.In this study, OVA (ovalbumin) was used as model antigen to be loaded in the as-prepared PLGA microparticles.The antigen release profile of microparticles incubated in PBS with different pH values (pH~ 7.4, 6.5 and 5.0) showed that the novel microparticles developed in this study demonstrated pH-responsive character which would rapidly release antigen in acidic environment.Next, we investigated the ability of these microparticles activate and maturate BMDCs in vitro.It was found that the expression of the co-stimulatory markers CD40 and CD86 was significantly up-regulated and induced higher secretion levels of IL-12p70, TNF-α and IL-6 than the conventional PLGA microparticles encapsulating antigen and antigen alone.The enhancement of immune response was further confirmed by immunization study in vivo using BALB/c mice.Specific IgG levels increased in all the immunized animals on days 7, 14, 28, 35 compared with the control group.The IgG levels of as-designed microparticles were much higher (p<0.05) than the group of conventional PLGA microparticles and antigen alone on day 28, 35.The results of cytokine suggested that the level of IFN-γ was evidently elevated by immunizing the pH-sensitive PLGA microparticles.In conclusion, the novel pH-sensitive PLGA microparticles possessed the ideal properties for activating and maturating the DCs and offered excellent humoral and cellular immune protection, which showed great potential as vaccine adjuvants and delivery systems.