A minimally designed PD-L1-targeted nanocomposite for positive feedback-based multimodal cancer therapy |
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| Affiliation: | 1. State Key Laboratory of Natural Medicines, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China;2. NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, Nanjing 210009, PR China;3. Department of Pharmaceutical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China;1. Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China;2. Department of Hepatobiliary and Pancreatic Surgery the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China;3. Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou 311121, China;4. CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China;5. Department of Cell Biology, School of Medicine, Zhejiang University, Hangzhou, 310058, China;6. Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China;7. Jinhua Institute of Zhejiang University, Jinhua 321299, China;8. MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China;1. Department of Minimally Invasive Interventional Radiology, the State Key Laboratory of Respiratory Disease, School of Biomedical Engineering & The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, P. R. China;2. Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China;3. Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region;4. School of Pharmaceutical Sciences, Capital Medical University, Beijing, China;1. Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China;2. School of Science and Engineering, Shenzhen Key Laboratory of Functional Aggregate Materials, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, China;3. Department of Materials Science & Engineering, Hong Kong Institute for Advanced Study, City University of Hong Kong, Kowloon, Hong Kong 999077, China;4. Center for Advanced Materials Research, Advanced Institute of Natural Sciences, Beijing Normal University at Zhuhai, Zhuhai 519085, China;5. School of Chemistry and Chemical Engineering, Hefei University of Technology, Hefei 230009, China;6. Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research, Center for Tissue Restoration and Reconstruction and Institute for Advanced Study, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong 999077, China;7. Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates (South China University of Technology), Guangzhou 510640, China;1. Department of Chemical, Biomolecular, and Corrosion Engineering, The University of Akron, Ohio 44325, USA;2. College of Materials Science& Engineering, Zhejiang University of Technology, Hangzhou 310014, China;3. Institute of Industrial Catalysis, State Key Laboratory Breeding Base of Green-Chemical Synthesis Technology, College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310032, China;4. State Key Laboratory of Marine Resources Utilization in South China Sea, Hainan University, Haikou 570228, China;5. School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China;6. Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China;1. Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 199 Ren''ai Road, Suzhou 215123, Jiangsu, PR China;2. Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China;1. Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, PR China;2. Institute for Advanced Studies, Wuhan University, Wuhan, 430072, PR China;3. Wuhan Research Centre for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, 430071, PR China |
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| Abstract: | Combining immune checkpoint blockade therapy (ICBT) with other treatment modalities through nanotechnology offers an opportunity to further boost immunity for effective cancer treatment. Herein three-in-one programmed death-ligand 1 (PD-L1)-targeted nanocomposite (NC) was minimally fabricated through self-assembling photothermal agent black phosphorus nanosheet (BPN), chemotherapeutic agent Polymetformin (PolyMet), and immune checkpoint inhibitor anti-PD-L1 antibody (aPD-L1), avoiding the easy degradability of BPN through bridging the electrostatic interaction between PolyMet and BPN. The prepared aPD-L1-PolyMet/BPN NC could precisely target primary tumor through the interaction between aPD-L1 and PD-L1 based on ICBT, and the targeting efficacy was gradually reinforced due to the PD-L1 upregulation in tumor sites after photothermal therapy (PTT), ensuring positive feedback-mediated multimodal antitumor effect during continuous treatment loops. Moreover, the combinational therapy composed of photothermal immunotherapy (PIT), chemotherapy and ICBT strengthened the antitumor efficacy owing to their synergistic mechanism. Meanwhile, the generated positive feedback property during treatment displayed powerful antitumor effect, which not only inhibited primary and abscopal tumor progression, but also prevented tumor metastasis and promoted long-term tumor immune memory establishment. Therefore, this antitumor NC provided a prospective insight into the field of multimodal cancer therapy through rational and minimal design. |
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| Keywords: | PD-L1-targeted nanocomposite Positive feedback loop Immune checkpoint blockade therapy Black phosphorus nanosheet Polymetformin |
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