Surface Mineralization of Engineered Bacterial Outer Membrane Vesicles to Enhance Tumor Photothermal/Immunotherapy.

Gram-negative bacteria can naturally produce nanosized spherical outer membrane vesicles (OMVs) with a lipid bilayer membrane, possessing immunostimulatory capabilities to be potentially applied in tumor therapy. However, the systemic toxicity induced by pathogen-associated molecular patterns (PAMPs) of OMVs is the main obstacle for their clinical translation. Herein, melanin-loaded OMVs were produced with a genetic engineering strategy and further coated with calcium phosphate (CaP) to reduce their toxicity to enhance tumor treatment effects. Wild-type bacterium Escherichia coli Nissle 1917 (EcN) was genetically engineered to highly express tyrosinase to catalyze the intracellular synthesis of melanin, giving melanin-loaded OMVs (OMVMel). To reduce the systemic toxicity in tumor therapy, OMVMel was coated with CaP by surface mineralization to obtain OMVMel@CaP. In comparison with OMVMel, OMVMel@CaP showed lower systemic inflammatory responses in healthy mice and less damage to the liver, spleen, lung, and kidney, so the administration dose could be increased to enhance the antitumor effect. In the acidic tumor microenvironment, the CaP shell disintegrated to release OMVMel to trigger antitumor immune responses. Under costimulation of OMVMel acting as immunoadjuvants and the damage-associated molecular patterns (DAMPs) released by the photothermal effect, the efficiency of tumor photothermal/immunotherapy was largely boosted through promoting the infiltration of matured DCs, M1 macrophages, and activated CD8+ T cells, decreasing the ratio of MDSCs in tumors.

Engineered Extracellular Vesicles to Enhance Antigen Presentation for Boosting Light-Driven Tumor Immunotherapy.

Extracellular vesicles (EVs) have emerged as potential tools for tumor-target therapy accompanied with activating anticancer immune responses by serving as an integrated platform, but usually suffered from the limited cross presentation of tumor-associated antigen by dendritic cells (DCs). Here, a straightforward engineering strategy to construct heat shock proteins 70 (HSP70) highly expressed EVs incapsulated with Te nanoparticles (Te@EVsHSP70 ) for tumor photothermal therapy triggering improved immunotherapy is proposed. Tumor cells are firstly used as bioreactors for intracellular synthesis of Te nanoparticles, and NIR irradiation is subsequently introduced to upregulate the expression of HSP70 to give engineered Te@EVsHSP70 through exocytosis. Te@EVsHSP70 exhibits excellent photothermal performance and enhanced tumor antigen capture capability, which induces significant immunogenic death of tumor cells and improves DCs maturation both in vitro and in vivo. Thus, the engineered EVs demonstrate superior antitumor efficacy through photothermal effect and following provoked antitumor immune responses. This work provides a facile method to fabricate multifunctional EVs-based drug delivery system for improving photothermal-triggered tumor immunotherapy.

[Effectiveness of a school weight control program].

BACKGROUND: School-based health promotion programs have been shown to reduce the incidence of obesity in students and improve student physical fitness. However, few longitudinal evaluations of the effectiveness of such programs have been conducted. PURPOSE: The purpose of this study was to assess the effectiveness of an in-school weight control program. Data was collected prior to and after the school's summer vacation period. METHODS: The study utilized a one-group pretest-posttest design. Overweight and obese children from the fifth grade in an elementary school in Taipei City were selected as purposive samples. The study, which was conducted between March and June 2007, introduced general obesity concepts, taught basic nutrition education, and organized a physical activity program that comprised two 45-min exercise sessions during the week and one 30-min session activity each weekend. The obesity index assessed the body mass index (BMI) and waist-to-height ratio (WHtR), with physical fitness tests conducted before and after student summer vacations to assess achieved weight control results. The nonparametric test and repeat measure were used to assess weight control program effectiveness. RESULTS: After the weight control program, significant declines in BMI and WHtR (p < .001), significant improvements in 800-m run/walk (p < .01) and 1-minute sit-up tests (p < .05) were recorded. However, no significant comparative improvement was achieved on either obesity index or physical fitness test. CONCLUSIONS: Weight control programs represent an effective approach to reduce BMI and WHtR and improve physical fitness. An appropriate diet and exercise are important for school-aged children to maintain effective weight control and physical fitness health.