1.Expert consensus on COVID-19 vaccination for children with special medical conditions
Xiangshi WANG ; Tianxing FENG ; Jingjing LI ; Wenjie WANG ; Yanling GE ; Jinqiao SUN ; Zhuoying HUANG ; Xiang GUO ; Zhi LI ; Xiaodong SUN ; Mei ZENG
Shanghai Journal of Preventive Medicine 2023;35(8):840-854
Children with certain comorbidities and immunocompromising conditions are highly vulnerable to SARS-CoV-2 infection. Vaccination against SARS-CoV-2 is an important strategy to reduce death, critical illness and overall disease burden. With the evolving and increasing transmission of SARS-CoV-2, universal vaccination is essential to achieve this goal. Children with special medical conditions are considered as the priorities for SARS-CoV-2 vaccination. However, vaccine hesitancy towards the implementation of SARS-CoV-2 vaccination currently remains an urgent challenge. In order to promote the sustainable vaccination for those children in Shanghai as well as China, Shanghai municipal center for disease control and prevention, together with the national children’s medical center, children’s hospital of Fudan university and the expert group on immunization planning of the Shanghai preventive medicine association, organized a consensus expert working group to formulate the evidence-based recommendations and implementation suggestions for children with common chronic diseases, allergy history, diseases involving adverse events related to vaccination, and immunocompromising conditions, based on the published evidence of SARS-CoV-2 vaccination for populations and children with special medical conditions.
2.Light-controllable charge-reversal nanoparticles with polyinosinic-polycytidylic acid for enhancing immunotherapy of triple negative breast cancer.
Lei FANG ; Zitong ZHAO ; Jue WANG ; Ping XIAO ; Xiangshi SUN ; Yaping DING ; Pengcheng ZHANG ; Dangge WANG ; Yaping LI
Acta Pharmaceutica Sinica B 2022;12(1):353-363
Nucleic acid drugs are highly applicable for cancer immunotherapy with promising therapeutic effects, while targeting delivery of these drugs to disease lesions remains challenging. Cationic polymeric nanoparticles have paved the way for efficient delivery of nucleic acid drugs, and achieved stimuli-responsive disassembly in tumor microenvironment (TME). However, TME is highly heterogeneous between individuals, and most nanocarriers lack active-control over the release of loaded nucleic acid drugs, which will definitely reduce the therapeutic efficacy. Herein, we have developed a light-controllable charge-reversal nanoparticle (LCCN) with controlled release of polyinosinic-polycytidylic acid [Poly(I:C)] to treat triple negative breast cancer (TNBC) by enhanced photodynamic immunotherapy. The nanoparticles keep suitably positive charge for stable loading of Poly(I:C), while rapidly reverse to negative charge after near-infrared light irradiation to release Poly(I:C). LCCN-Poly(I:C) nanoparticles trigger effective phototoxicity and immunogenic cell death on 4T1 tumor cells, elevate antitumor immune responses and inhibit the growth of primary and abscopal 4T1 tumors in mice. The approach provides a promising strategy for controlled release of various nucleic acid-based immune modulators, which may enhance the efficacy of photodynamic immunotherapy against TNBC.
3.Acid-switchable nanoparticles induce self-adaptive aggregation for enhancing antitumor immunity of natural killer cells.
Xiangshi SUN ; Xiaoxuan XU ; Jue WANG ; Xinyue ZHANG ; Zitong ZHAO ; Xiaochen LIU ; Guanru WANG ; Lesheng TENG ; Xia CHEN ; Dangge WANG ; Yaping LI
Acta Pharmaceutica Sinica B 2023;13(7):3093-3105
Deficiency of natural killer (NK) cells shows a significant impact on tumor progression and failure of immunotherapy. It is highly desirable to boost NK cell immunity by upregulating active receptors and relieving the immunosuppressive tumor microenvironment. Unfortunately, mobilization of NK cells is hampered by poor accumulation and short retention of drugs in tumors, thus declining antitumor efficiency. Herein, we develop an acid-switchable nanoparticle with self-adaptive aggregation property for co-delivering galunisertib and interleukin 15 (IL-15). The nanoparticles induce morphology switch by a decomposition-metal coordination cascade reaction, which provides a new methodology to trigger aggregation. It shows self-adaptive size-enlargement upon acidity, thus improving drug retention in tumor to over 120 h. The diameter of agglomerates is increased and drug release is effectively promoted following reduced pH values. The nanoparticles activate both NK cell and CD8+ T cell immunity in vivo. It significantly suppresses CT26 tumor in immune-deficient BALB/c mice, and the efficiency is further improved in immunocompetent mice, indicating that the nanoparticles can not only boost innate NK cell immunity but also adaptive T cell immunity. The approach reported here provides an innovative strategy to improve drug retention in tumors, which will enhance cancer immunotherapy by boosting NK cells.