Programmable Bispecific Nano-immunoengager That Captures T Cells and Reprograms Tumor Microenvironment

Zhang，Lu1,2; Bo，Ruonan1; Wu，Yi1; Li，Longmeng1; Zhu，Zheng1; Ma，Ai Hong1; Xiao，Wenwu1; Huang，Yanyu1; Rojalin，Tatu1; Yin，Xingbin1; Mao，Chunping2; Wang，Fengyi2; Wang，Yongheng1; Zhang，Hongyong1; Low，Kelmen E.1; Lee，Kiana1; Ajena，Yousif1; Jing，Di1; Zhang，Dalin1; Baehr，Christopher M.1; Liu，Ruiwu1; Wang，Lei3; Li，Yuanpei1; Lam，Kit S.1,4

2022

10.1021/acs.nanolett.2c00582

NANO LETTERS   Impact Factor & Quartile

1530-6984

1530-6992

Immune checkpoint blockade (ICB) therapy has revolutionized clinical oncology. However, the efficacy of ICB therapy is limited by the ineffective infiltration of T effector (Teff) cells to tumors and the immunosuppressive tumor microenvironment (TME). Here, we report a programmable tumor cells/Teff cells bispecific nano-immunoengager (NIE) that can circumvent these limitations to improve ICB therapy. The peptidic nanoparticles (NIE-NPs) bind tumor cell surface α3β1 integrin and undergo in situ transformation into nanofibrillar network nanofibers (NIE-NFs). The prolonged retained nanofibrillar network at the TME captures Teff cells via the activatable α4β1 integrin ligand and allows sustained release of resiquimod for immunomodulation. This bispecific NIE eliminates syngeneic 4T1 breast cancer and Lewis lung cancer models in mice, when given together with anti-PD-1 antibody. The in vivo structural transformation-based supramolecular bispecific NIE represents an innovative class of programmable receptor-mediated targeted immunotherapeutics to greatly enhance ICB therapy against cancers.

fibrillar transformation immune checkpoint blockade (ICB) therapy nano-immuno-engager T cells capture

SCI ; EI

English

NI Journal Papers

Corresponding

NIH["R01CA115483","U01CA198880","R01CA247683","R01EB012569","R01CA232845","R01DE029237"] ; National Key R&D Program of China[2018YFE0205400]

Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics

Chemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied ; Physics, Condensed Matter

WOS:000860449000001

AMER CHEMICAL SOC

20223412590762

Cell membranes ; Cytology ; Diseases ; Mammals ; Tumors

Biological Materials and Tissue Engineering:461.2 ; Biology:461.9 ; Immunology:461.9.1

MATERIALS SCIENCE

2-s2.0-85136032142

Scopus

1.Department of Biochemistry and Molecular Medicine,UC Davis NCI-designated Comprehensive Cancer Center,University of California Davis,Sacramento,95817,United States
2.Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen,Guangdong,518055,China
3.CAS Center for Excellence in Nanoscience,CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety,National Center for Nanoscience and Technology,Beijing,100190,China
4.Division of Hematology and Oncology,Department of Internal Medicine,School of Medicine,University of California Davis,Sacramento,95817,United States

Zhang，Lu,Bo，Ruonan,Wu，Yi,et al. Programmable Bispecific Nano-immunoengager That Captures T Cells and Reprograms Tumor Microenvironment[J]. NANO LETTERS,2022,22(17).

Zhang，Lu.,Bo，Ruonan.,Wu，Yi.,Li，Longmeng.,Zhu，Zheng.,...&Lam，Kit S..(2022).Programmable Bispecific Nano-immunoengager That Captures T Cells and Reprograms Tumor Microenvironment.NANO LETTERS,22(17).

Zhang，Lu,et al."Programmable Bispecific Nano-immunoengager That Captures T Cells and Reprograms Tumor Microenvironment".NANO LETTERS 22.17(2022).