KERS-Inspired Nanostructured Mineral Coatings Boost IFN-γ mRNA Therapeutic Index for Antitumor Immunotherapy.

Autor: Shao Z; Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Orthopedics Research Institute of Zhejiang University, Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Clinical Research Center of Motor System Disease of Zhejiang Province, 88 Jiefang Road, Hangzhou City, Zhejiang Province, 310003, P. R. China., Chen L; Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Orthopedics Research Institute of Zhejiang University, Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Clinical Research Center of Motor System Disease of Zhejiang Province, 88 Jiefang Road, Hangzhou City, Zhejiang Province, 310003, P. R. China., Zhang Z; Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Orthopedics Research Institute of Zhejiang University, Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Clinical Research Center of Motor System Disease of Zhejiang Province, 88 Jiefang Road, Hangzhou City, Zhejiang Province, 310003, P. R. China., Wu Y; Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Orthopedics Research Institute of Zhejiang University, Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Clinical Research Center of Motor System Disease of Zhejiang Province, 88 Jiefang Road, Hangzhou City, Zhejiang Province, 310003, P. R. China., Mou H; Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Orthopedics Research Institute of Zhejiang University, Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Clinical Research Center of Motor System Disease of Zhejiang Province, 88 Jiefang Road, Hangzhou City, Zhejiang Province, 310003, P. R. China., Jin X; Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Orthopedics Research Institute of Zhejiang University, Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Clinical Research Center of Motor System Disease of Zhejiang Province, 88 Jiefang Road, Hangzhou City, Zhejiang Province, 310003, P. R. China., Teng W; Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Orthopedics Research Institute of Zhejiang University, Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Clinical Research Center of Motor System Disease of Zhejiang Province, 88 Jiefang Road, Hangzhou City, Zhejiang Province, 310003, P. R. China., Wang F; Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Orthopedics Research Institute of Zhejiang University, Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Clinical Research Center of Motor System Disease of Zhejiang Province, 88 Jiefang Road, Hangzhou City, Zhejiang Province, 310003, P. R. China., Yang Y; College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China., Zhou H; Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Orthopedics Research Institute of Zhejiang University, Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Clinical Research Center of Motor System Disease of Zhejiang Province, 88 Jiefang Road, Hangzhou City, Zhejiang Province, 310003, P. R. China., Xue Y; Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Orthopedics Research Institute of Zhejiang University, Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Clinical Research Center of Motor System Disease of Zhejiang Province, 88 Jiefang Road, Hangzhou City, Zhejiang Province, 310003, P. R. China., Eloy Y; Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Orthopedics Research Institute of Zhejiang University, Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Clinical Research Center of Motor System Disease of Zhejiang Province, 88 Jiefang Road, Hangzhou City, Zhejiang Province, 310003, P. R. China., Yao M; Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Orthopedics Research Institute of Zhejiang University, Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Clinical Research Center of Motor System Disease of Zhejiang Province, 88 Jiefang Road, Hangzhou City, Zhejiang Province, 310003, P. R. China., Zhao S; Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Orthopedics Research Institute of Zhejiang University, Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Clinical Research Center of Motor System Disease of Zhejiang Province, 88 Jiefang Road, Hangzhou City, Zhejiang Province, 310003, P. R. China., Cui W; Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, P. R. China., Yu X; Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Orthopedics Research Institute of Zhejiang University, Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Clinical Research Center of Motor System Disease of Zhejiang Province, 88 Jiefang Road, Hangzhou City, Zhejiang Province, 310003, P. R. China., Ye Z; Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Orthopedics Research Institute of Zhejiang University, Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Clinical Research Center of Motor System Disease of Zhejiang Province, 88 Jiefang Road, Hangzhou City, Zhejiang Province, 310003, P. R. China.
Jazyk: angličtina
Zdroj: Advanced materials (Deerfield Beach, Fla.) [Adv Mater] 2023 Dec; Vol. 35 (51), pp. e2304296. Date of Electronic Publication: 2023 Oct 27.
DOI: 10.1002/adma.202304296
Abstrakt: Tumor-associated macrophage (TAM) reprogramming is a promising therapeutic approach for cancer immunotherapy; however, its efficacy remains modest due to the low bioactivity of the recombinant cytokines used for TAM reprogramming. mRNA therapeutics are capable of generating fully functional proteins for various therapeutic purposes but accused for its poor sustainability. Inspired by kinetic energy recovery systems (KERS) in hybrid vehicles, a cytokine efficacy recovery system (CERS) is designed to substantially augment the therapeutic index of mRNA-based tumor immunotherapy via a "capture and stabilize" mechanism exerted by a nanostructured mineral coating carrying therapeutic cytokine mRNA. CERS remarkably recycles nearly 40% expressed cytokines by capturing them onto the mineral coating to extend its therapeutic timeframe, further polarizing the macrophages to strengthen their tumoricidal activity and activate adaptive immunity against tumors. Notably, interferon-γ (IFN-γ) produced by CERS exhibits ≈42-fold higher biological activity than recombinant IFN-γ, remarkably decreasing the required IFN-γ dosage for TAM reprogramming. In tumor-bearing mice, IFN-γ cmRNA@CERS effectively polarizes TAMs to inhibit osteosarcoma progression. When combined with the PD-L1 monoclonal antibody, IFN-γ cmRNA@CERS significantly boosts antitumor immune responses, and substantially prevents malignant lung metastases. Thus, CERS-mediated mRNA delivery represents a promising strategy to boost antitumor immunity for tumor treatment.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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