Halofuginone-guided nano-local therapy: Nano-thermosensitive hydrogels for postoperative metastatic canine mammary carcinoma with scar removal

Runan Zuo; Lingqing Kong; Wanjun Pang; Shanxiang Jiang

doi:10.1016/j.ijpx.2024.100241

Halofuginone-guided nano-local therapy: Nano-thermosensitive hydrogels for postoperative metastatic canine mammary carcinoma with scar removal

Int J Pharm X. 2024 Mar 26:7:100241. doi: 10.1016/j.ijpx.2024.100241. eCollection 2024 Jun.

Authors

Runan Zuo^{1

2}, Lingqing Kong¹, Wanjun Pang¹, Shanxiang Jiang²

Affiliations

¹ 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.
² 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.

Abstract

In female dogs, the highest morbidity and mortality rates cancer are the result of mammary adenocarcinoma, which presents with metastases in the lung. Other than early surgical removal, however, no special methods are available to treat mammary adenocarcinoma. Because human breast cancer and canine mammary carcinoma share clinical characteristics and heterogeneity, the canine model is a suitable spontaneous tumor model for breast cancer in humans. In this study, the physical swelling method was used to prepare halofuginone-loaded D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) polymer micelles nano-thermosensitive hydrogels (HTPM-gel). Furthermore, HTPM-gel was investigated via characterization, morphology, properties such as swelling experiment and in vitro release with reflecting its splendid nature. Moreover, HTPM-gel was further examined its capability to anti-proliferation, anti-migration, and anti-invasion. Ultimately, HTPM-gel was investigated for its in vivo anticancer activity in the post-operative metastatic and angiogenic canine mammary carcinoma. HTPM-gel presented spherical under transmission electron microscope (TEM) and represented grid structure under scanning electron microscope (SEM), with hydrodynamic diameter (HD) of 20.25 ± 2.5 nm and zeta potential (ZP) of 15.10 ± 1.82 mV. Additionally, HTPM-gel own excellent properties comprised of pH-dependent swelling behavior, sustained release behavior. To impede the migration, invasion, and proliferation of CMT-U27 cells, we tested the efficacy of HTPM-gel. Evaluation of in vivo anti-tumor efficacy demonstrates HTPM-gel exhibit a splendid anti-metastasis and anti-angiogenic ability, with exhibiting ideal biocompatibility. Notably, HTPM-gel also inhibited the scar formation in the healing process after surgery. In summary, HTPM-gel exhibited anti-metastasis and anti-angiogenic and scar repair features. According to the results of this study, HTPM-gel has encouraging clinical potential to treat tumors with multifunctional hydrogel.

Keywords: Angiogenesis; Halofuginone; Metastasis; Postoperative; Scar removal; Thermosensitive hydrogels.