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

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Histone deacetylase inhibitors (HDACi) show promise in cancer treatment by inhibiting tumor metastasis.
• Vorinostat (SAHA) is an approved HDACi, but faces challenges like poor solubility and low cellular penetration.
• Existing drug carriers have limitations for effective HDACi delivery.

Purpose of the Study:

• To fabricate a folate and vorinostat bound BSA nanogel (FVBN) for improved solubility, stability, cellular uptake, and targeted release.
• To evaluate the efficacy of FVBN in inhibiting cancer cell growth, migration, and metastasis.
• To assess the in vivo antitumor activity and safety profile of FVBN in preclinical cancer models.

Main Methods:

• Fabrication of folate and vorinostat bound BSA nanogel (FVBN).
• In vitro studies assessing cellular uptake, cytotoxicity, and cell cycle arrest.
• In vivo experiments using melanoma and ovarian cancer models in nude mice.

Main Results:

• FVBN demonstrated good dispersion and stability, enhancing vorinostat cellular uptake via folate-mediated endocytosis.
• FVBN exhibited comparable cytotoxicity to free SAHA, inducing G1/G0 phase cell cycle arrest.
• FVBN effectively inhibited melanoma growth and pulmonary metastasis, and showed significant antitumor effects in ovarian cancer models without liver damage.

Conclusions:

• FVBN represents a promising drug delivery system for HDACi, overcoming limitations of free SAHA.
• The gelated and inner-lysosome triggered release strategy of FVBN enhances therapeutic efficacy and safety.
• FVBN holds potential for expanding the clinical application of HDAC inhibitors in cancer therapy.