Qingqin Tan1,2,3, Lingjie He1,2,3, Xiaojun Meng4, Wei Wang1, Hudan Pan5, Weiguo Yin6, Tianchuan Zhu1, Xi Huang7,8,9,10, Hong Shan11. 1. Center for Infection and Immunity, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China. 2. Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai, 519000, Guangdong, China. 3. Key Laboratory of Tropical Diseases Control, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China. 4. Department of Endocrinology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China. 5. Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao, 999078, China. 6. The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, 511518, Guangdong, China. 7. Center for Infection and Immunity, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China. huangxi6@mail.sysu.edu.cn. 8. Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai, 519000, Guangdong, China. huangxi6@mail.sysu.edu.cn. 9. Key Laboratory of Tropical Diseases Control, Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, Guangdong, China. huangxi6@mail.sysu.edu.cn. 10. The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, 511518, Guangdong, China. huangxi6@mail.sysu.edu.cn. 11. Center for Infection and Immunity, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China. shanhong@mail.sysu.edu.cn.
Abstract
BACKGROUND: The worldwide pandemic of COVID-19 remains a serious public health menace as the lack of efficacious treatments. Cytokine storm syndrome (CSS) characterized with elevated inflammation and multi-organs failure is closely correlated with the bad outcome of COVID-19. Hence, inhibit the process of CSS by controlling excessive inflammation is considered one of the most promising ways for COVID-19 treatment. RESULTS: Here, we developed a biomimetic nanocarrier based drug delivery system against COVID-19 via anti-inflammation and antiviral treatment simultaneously. Firstly, lopinavir (LPV) as model antiviral drug was loaded in the polymeric nanoparticles (PLGA-LPV NPs). Afterwards, macrophage membranes were coated on the PLGA-LPV NPs to constitute drugs loaded macrophage biomimetic nanocarriers (PLGA-LPV@M). In the study, PLGA-LPV@M could neutralize multiple proinflammatory cytokines and effectively suppress the activation of macrophages and neutrophils. Furthermore, the formation of NETs induced by COVID-19 patients serum could be reduced by PLGA-LPV@M as well. In a mouse model of coronavirus infection, PLGA-LPV@M exhibited significant targeted ability to inflammation sites, and superior therapeutic efficacy in inflammation alleviation and tissues viral loads reduction. CONCLUSION: Collectively, such macrophage biomimetic nanocarriers based drug delivery system showed favorable anti-inflammation and targeted antiviral effects, which may possess a comprehensive therapeutic value in COVID-19 treatment.
BACKGROUND: The worldwide pandemic of COVID-19 remains a serious public health menace as the lack of efficacious treatments. Cytokine storm syndrome (CSS) characterized with elevated inflammation and multi-organs failure is closely correlated with the bad outcome of COVID-19. Hence, inhibit the process of CSS by controlling excessive inflammation is considered one of the most promising ways for COVID-19 treatment. RESULTS: Here, we developed a biomimetic nanocarrier based drug delivery system against COVID-19 via anti-inflammation and antiviral treatment simultaneously. Firstly, lopinavir (LPV) as model antiviral drug was loaded in the polymeric nanoparticles (PLGA-LPV NPs). Afterwards, macrophage membranes were coated on the PLGA-LPV NPs to constitute drugs loaded macrophage biomimetic nanocarriers (PLGA-LPV@M). In the study, PLGA-LPV@M could neutralize multiple proinflammatory cytokines and effectively suppress the activation of macrophages and neutrophils. Furthermore, the formation of NETs induced by COVID-19patients serum could be reduced by PLGA-LPV@M as well. In a mouse model of coronavirus infection, PLGA-LPV@M exhibited significant targeted ability to inflammation sites, and superior therapeutic efficacy in inflammation alleviation and tissues viral loads reduction. CONCLUSION: Collectively, such macrophage biomimetic nanocarriers based drug delivery system showed favorable anti-inflammation and targeted antiviral effects, which may possess a comprehensive therapeutic value in COVID-19 treatment.
Authors: Maroun Khoury; Jimena Cuenca; Fernanda F Cruz; Fernando E Figueroa; Patricia R M Rocco; Daniel J Weiss Journal: Eur Respir J Date: 2020-06-04 Impact factor: 16.671