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Abstract Despite the promise and advantages of autologous cancer cell vaccination, it remains challenging to induce potent anti-tumor immune responses with traditional immunization strategies with whole tumor cell lysate. In this study, we sought to develop a simple and effective approach for therapeutic vaccination with autologous whole tumor cell lysate. Endogenous cell membranes harvested from cancer cells were formed into PEGylated nano-vesicles (PEG-NPs). PEG-NPs exhibited good serum stability in vitro and draining efficiency to local lymph nodes upon subcutaneous administration in vivo. Vaccination with PEG-NPs synthesized from murine melanoma cells elicited 3.7-fold greater antigen-specific cytotoxic CD8+ T lymphocyte responses, compared with standard vaccination with freeze-thawed lysate in tumor-bearing mice. Importantly, in combination with anti-programmed death-1 (αPD-1) IgG immunotherapy, PEG-NP vaccination induced 4.2-fold higher frequency of antigen-specific T cell responses (P < 0.0001) and mediated complete tumor regression in 63% of tumor-bearing animals (P < 0.01), compared with FT lysate + αPD-1 treatment that exhibited only 13% response rate. In addition, PEG-NPs + αPD-1 IgG combination immunotherapy protected all survivors against a subsequent tumor cell re-challenge. These results demonstrate a general strategy for eliciting anti-tumor immunity using endogenous cancer cell membranes formulated into stable vaccine nanoparticles. [ABSTRACT FROM AUTHOR]

Abstract: Mesoporous silica spheres with controllable particle size were synthesized in mixed ethanol–water solvent. These materials possessed same pore size distribution and pore channel geometry. The amount of ibuprofen (IBU) adsorbed in mesoporous channels increased with the surface area of mesoporous silica spheres. Three kinds of release fluids, simulated intestinal fluid (SIF, pH=7.4), simulated body fluid (SBF, pH=7.4), and simulated gastric fluid (SGF, HCl aqueous solution, pH=1.2) were used to investigate drug release. The effects of particle size and dispersancy of mesoporous spheres on drug release rate were discussed in detail. It was found that larger or agglomerate mesoporous silica spheres could delay the drug release process, which could be attributed to pore-mouth amount and mesopore channel length of mesoporous spheres. Furthermore, to obtain a well controlled drug release system, hydrophobic trimethylsilyl (TMS) groups were functionalized on the surface of mesoporous silica spheres. The release of IBU from TMS-functionalized mesoporous spheres was obviously delayed with the increase of TMS content. [Copyright &y& Elsevier]

Abstract: A simple pH-controlled drug release system was successfully prepared by coating pH-sensitive polymer hydroxypropyl methylcellulose phthalate (HPMCP) on drug-loaded mesoporous SBA-15 tablet. Using famotidine (Famo) as a model drug, the effects of coating times and drying temperature on drug release were studied in detail to optimize the drug release system. In simulated gastric fluid (SGF, pH 1.2), it took only 2h for Famo to be completely released from mesoporous silica tablet without HPMCP coating. Also in SGF, with the increase of coating times and drying temperature, the release of Famo was greatly delayed by HPMCP coating. For the tablet with twice coating of HPMCP and dried at 80°C, only 4.0wt.% of Famo could be released within 4h. However, in simulated intestinal fluid (SIF, pH 7.4), HPMCP coating did not show obvious effect on the release of Famo. [Copyright &y& Elsevier]

Abstract: Dimethylsilyl (DMS) modified mesoporous silicas were successfully prepared via co-condensation and post-grafting modification methods. The post-grafting modification was carried out by the reaction of the as-synthesized MCM-41 material (before CTAB removal) with diethoxydimethylsinale (DEDMS). N2 adsorption–desorption and 29Si MAS NMR characterization demonstrated that different amount of DMS groups were successfully incorporated into the co-condensation modified samples, and the functional DMS groups were placed selectively on the pore openings and external pore surfaces in the post-grafting modified samples. Subsequently, the controlled drug delivery properties from the resulting DMS-modified mesoporous silicas were investigated in detail. The drug adsorption experiments showed that the adsorption capacities were mainly depended on the content of silanol group (CSG) in the corresponding carriers. The in vitro tests exhibited that the incorporation of DMS groups greatly retarded the ibuprofen release rate. Moreover, the ibuprofen release profiles could be well modulated by varying DMS modification levels and site-selective distribution of functional groups in mesoporous carriers. [Copyright &y& Elsevier]