Postoperative distant metastasis and high recurrence rate causes a dilemma in treating triple-negative breast cancer (TNBC) owing to its unforeseeable invasion into various organs or tissues. The wealth of nutrition provided by vascular may facilitate the proliferation and angiogenesis of cancer cells, which further enhance the rates of postoperative metastasis and recurrence. Chemotherapy, as a systemic postoperative adjuvant therapy, is generally applied to diminish recurrence and metastasis of TNBC. Herein, an halofuginone-silver nano thermosensitive hydrogel (HTPM&AgNPs-gel) was prepared via a physical swelling method. The in vitro anticancer efficacy of HTPM&AgNPs-gel was analyzed by investigating cell proliferation, migration, invasion, and angiogenesis capacity. Furthermore, the in vivo anti-cancer activity of HTPM&AgNPs-gel was further appraised through the tumor suppression, anti-metastatic, anti-angiogenic, and anti-inflammatory ability. The optimized HTPM&AgNPs-gel, a thermosensitive hydrogel, showed excellent properties, including syringeability, swelling behavior, and a sustained release effect without hemolysis. In addition, HTPM&AgNPs-gel was confirmed to effectively inhibit the proliferation, migration, invasion, and angiogenesis of MDA-MB-231 cells. An evaluation of the in vivo anti-tumor efficacy demonstrated that HTPM&AgNPs-gel showed a stronger tumor inhibition rate (68.17%) than did HTPM-gel or AgNPs-gel used alone and exhibited outstanding biocompatibility. Notably, HTPM&AgNPs-gel also inhibited lung metastasis induced by residual tumor tissue after surgery and further blocked angiogenesis-related inflammatory responses. Taken together, the suppression of inflammation by interdicting the blood vessels adjoining the tumor and inhibiting angiogenesis is a potential strategy to attenuate the recurrence and metastasis of TNBC. HTPM&AgNPs-gel is a promising anticancer agent for TNBC as a local postoperative treatment.

Animal Derived Food Safety Innovation Team College of Animal Science and Technology Anhui Province Key Lab of Veterinary Pathobiology and Disease Control Anhui Agricultural University Hefei Anhui 230036 PR China; Engineering Center of Innovative Veterinary Drugs Center for Veterinary Drug Research and Evaluation MOE Joint International Research Laboratory of Animal Health and Food Safety College of Veterinary Medicine Nanjing Agricultural University 1 Weigang Nanjing 210095 PR China

Department of Chemistry Faculty of Science University of Hradec Kralove Hradec Kralove Czech Republic

Department of Chemistry Faculty of Science University of Hradec Kralove Hradec Kralove Czech Republic; Biomedical Research Center University Hospital Hradec Kralove 50003 Hradec Kralove Czech Republic; Andalusian Research Institute in Data Science and Computational Intelligence University of Granada Granada Spain

Engineering Center of Innovative Veterinary Drugs Center for Veterinary Drug Research and Evaluation MOE Joint International Research Laboratory of Animal Health and Food Safety College of Veterinary Medicine Nanjing Agricultural University 1 Weigang Nanjing 210095 PR China

School of Food and Biological Engineering Hefei University of Technology Hefei 230009 PR China

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