Redox-Responsive Gold Nanoparticles Coated with Hyaluronic Acid and Folic Acid for Application in Targeting Anticancer Therapy

• Published in: Molecules (Basel, Switzerland) Vol. 29; no. 7; p. 1564
• Main Authors: Munderere, Raissa, Gulfam, Muhammad, Ali, Israr, Kim, Seon-Hwa, Vu, Trung Thang, Park, Sang-Hyug, Lim, Kwon Taek
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.04.2024
• Subjects: Biocompatibility; Cancer; Cancer therapies; Care and treatment; Cervical cancer; Chemical bonds; Chemical properties; Chemotherapy; Cytotoxicity; Dihydrofolate reductase; drug delivery; Drug delivery systems; dual target; Folic Acid; Glutathione; Gold; gold nanoparticles; HEK293 Cells; Humans; Hyaluronic Acid; hybrid; Ligands; Metal Nanoparticles; methotrexate; Methotrexate - pharmacology; Nanoparticles; Physiology; Toxicity; Vitamin B; South Korea; methotrexate; hybrid; drug delivery; dual target; gold nanoparticles
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules29071564

Methotrexate (MTX) has poor water solubility and low bioavailability, and cancer cells can become resistant to it, which limits its safe delivery to tumor sites and reduces its clinical efficacy. Herein, we developed novel redox-responsive hybrid nanoparticles (NPs) from hyaluronic acid (HA) and 3-mercaptopropionic acid (MPA)-coated gold NPs (gold@MPA NPs), which were further conjugated with folic acid (FA). The design of FA-HA-ss-gold NPs aimed at enhancing cellular uptake specifically in cancer cells using an active FA/HA dual targeting strategy for enhanced tumor eradication. MTX was successfully encapsulated into FA-HA-ss-gold NPs, with drug encapsulation efficiency (EE) as high as >98.7%. The physicochemical properties of the NPs were investigated in terms of size, surface charges, wavelength reflectance, and chemical bonds. MTX was released in a sustained manner in glutathione (GSH). The cellular uptake experiments showed effective uptake of FA-HA-ss-gold over HA-ss-gold NPs in the deep tumor. Moreover, the release studies provided strong evidence that FA-HA-ss-gold NPs serve as GSH-responsive carriers. In vitro, anti-tumor activity tests showed that FA-HA-ss-gold/MTX NPs exhibited significantly higher cytotoxic activity against both human cervical cancer (HeLa) cells and breast cancer (BT-20) cells compared to gold only and HA-ss-gold/MTX NPs while being safe for human embryonic kidney (HEK-293) cells. Therefore, this present study suggests that FA-HA-ss-gold NPs are promising active targeting hybrid nanocarriers that are stable, controllable, biocompatible, biodegradable, and with enhanced cancer cell targetability for the safe delivery of hydrophobic anticancer drugs.