Affiliation:
1. State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China
2. School of Pharmacy Fudan University Shanghai 201203 China
3. Department of Breast Surgery Shanghai Pudong Hospital Fudan University Pudong Medical Center Shanghai 201399 China
4. Artificial Intelligence Innovation and Incubation Institute Fudan University Shanghai 200433 China
5. State Key Laboratory of Genetic Engineering School of Life Sciences & Human Phenome Institute Fudan University Shanghai 200433 China
6. Bohai Rim Advanced Research Institute for Drug Discovery Yantai Shandong 264005 China
Abstract
AbstractThe immunomodulatory effects of many therapeutic agents are significantly challenged by their insufficient delivery efficiency and short retention time in tumors. Regarding the distinctively upregulated fibronectin (FN1) and tenascin C (TNC) in tumor stroma, herein a protease‐activated FN1 and/or TNC binding peptide (FTF) is designed and an extracellular matrix (ECM)‐trapped bioinspired lipoprotein (BL) (FTF‐BL‐CP) is proposed that can be preferentially captured by the TNC and/or FN1 for tumor retention, and then be responsively dissociated from the matrix to potentiate the antitumor immunity. The FTF‐BL‐CP treatment produces a 6.96‐, 9.24‐, 6.72‐, 7.32‐, and 6.73‐fold increase of CD3+CD8+ T cells and their interferon‐γ‐, granzyme B‐, perforin‐, and Ki67‐expressing subtypes versus the negative control, thereby profoundly eliciting the antitumor immunity. In orthotopic and lung metastatic breast cancer models, FTF‐BL‐CP produces notable therapeutic benefits of retarding tumor growth, extending survivals, and inhibiting lung metastasis. Therefore, this ECM‐trapping strategy provides an encouraging possibility of prolonging tumor retention to potentiate the antitumor immunity for anticancer immunotherapy.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
University of Washington College of Arts and Sciences