1.Reimaging biological barriers affecting distribution and extravasation of PEG/peptide- modified liposomes in xenograft SMMC7721 tumor.
Hailing TANG ; Mengjie RUI ; Junhua MAI ; Wei GUO ; Yuhong XU
Acta Pharmaceutica Sinica B 2020;10(3):546-556
Liposomes, as one of the most successful nanotherapeutics, have a major impact on many biomedical areas. In this study, we performed laser scanning confocal microscope (LSCM) and immunohistochemistry (IHC) assays to investigate the intra-tumor transport and antitumor mechanism of GE11 peptide-conjugated active targeting liposomes (GE11-TLs) in SMMC7721 xenograft model. According to classification of individual cell types in high resolution images, biodistribution of macrophages, tumor cells, cells with high epidermal growth factor receptor (EGFR) expression and interstitial matrix in tumor microenvironment, in addition, their impacts on intra-tumor penetration of GE11-TLs were estimated. Type I collagen fibers and macrophage flooded in the whole SMMC7721 tumor xenografts. Tumor angiogenesis was of great heterogeneity from the periphery to the center region. However, the receptor-binding site barriers were supposed to be the leading cause of poor penetration of GE11-TLs. We anticipate these images can give a deep reconsideration for rational design of target nanoparticles for overcoming biological barriers to drug delivery.
2.An mRNA vaccine elicits STING-dependent antitumor immune responses.
Zhe CHEN ; Chaoyang MENG ; Junhua MAI ; Yongbin LIU ; Hangwen LI ; Haifa SHEN
Acta Pharmaceutica Sinica B 2023;13(3):1274-1286
Lipid-formulated RNA vaccines have been widely used for disease prevention and treatment, yet their mechanism of action and individual components contributing to such actions remain to be delineated. Here, we show that a therapeutic cancer vaccine composed of a protamine/mRNA core and a lipid shell is highly potent in promoting cytotoxic CD8+ T cell responses and mediating anti-tumor immunity. Mechanistically, both the mRNA core and lipid shell are needed to fully stimulate the expression of type I interferons and inflammatory cytokines in dendritic cells. Stimulation of interferon-β expression is exclusively dependent on STING, and antitumor activity from the mRNA vaccine is significantly compromised in mice with a defective Sting gene. Thus, the mRNA vaccine elicits STING-dependent antitumor immunity.
3.Adsorptive hemofiltration for sepsis management: expert recommendations based on the Asia Pacific experience.
Ling ZHANG ; Matthew COVE ; Binh G NGUYEN ; Nuttha LUMLERTGUL ; Kartik GANESH ; Alfred CHAN ; Giang T H BUI ; Chunwen GUO ; Junhua LI ; Songqiao LIU ; Mian PENG ; Kit W FOONG ; Jian ZHANG ; Minmin WANG ; Jacques GOLDSTEIN ; Kai HARENSKI
Chinese Medical Journal 2021;134(18):2258-2260