Gelated Vorinostat with inner-lysosome triggered release for tumor-targeting chemotherapy

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 194; p. 111144
• Main Authors: Guo, Changyong, Wang, Qirong, Zhang, Xingjie, Lu, Fengkun, Sun, Miao, Zeng, Peiyu, Sun, Linhong, She, Lan, Wang, Bingkai, Zhang, Yunchang, Wang, Chen, Ma, Zhiqiang, Yang, Feng
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2020
• Subjects: HDACi; Nanogel; Suberoylanilide hydroxamic acid; Vorinostat; Nanogel; HDACi; Vorinostat; Suberoylanilide hydroxamic acid
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2020.111144

[Display omitted] •A nanogel of vorinostat with inner-lysosome triggered release was prepared.•FVBN enhanced the antitumor-effect of vorinostat with lower toxicity in vitro and in vivo.•FVBN significantly suppressed tumor metastasis against mice-bearing melanoma.•FVBN is promising to expand the scope of application of HDACi in clinical cancer therapy. Histonedeacetylase inhibitor (HDACi) has great potential in targeted antitumor therapy by inhibiting tumor migration, invasion, and metastasis. As one of the typical HDACis, vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) was approved as a therapeutic agent for cancer therapy, however, challenges remain due to their poor solubility, short half-life and low efficiency in cellular penetration. Considering the disadvantages of usual drug carriers, folate and vorinostat bound BSA nanogel (FVBN)was fabricated to implement higher solubility, stability, cellular uptake, and lipase-responsive release. With good dispersion and stability, FVBN significantly increased the cellular uptake of vorinostat through folate-mediated endocytosis. FVBN exhibited comparable cytotoxicity with free SAHA, and the growth of tumor cells was blocked in G1/G0 phase just like SAHA performed in cell cycle arrest tests. Moreover, FVBN not only effectively inhibited the growth of melanoma but also observably prevented pulmonary metastasis of melanoma. In the experiment against nude mice bearing solid ovarian cancer, FVBN showed excellent antitumor effect without liver damage, demonstrating the superiority of gelated and inner-lysosome triggered release strategies to the free SAHA, and it is promising to expand the scope of application of HDACi in clinical cancer therapy.