Room temperature synthesis of β-cyclodextrin functionalized graphene oxide decorated MIL-100 (Fe): A sustainable drug cargo for anticancer drug delivery

Abstract

Chemotherapy remains an extensively used cancer treatment method with the accessibility of various chemotherapeutic agents. However, its effectiveness is limited by the inability to distinguish between precipitously propagating normal cells and cancer cells, leading to severe side effects. Targeted drug delivery systems (DDS), utilizing advanced nanomaterials such as nanocarriers and natural/green chemotherapeutic agents like caffeic acid (CA), offer a promising solution to overcome these challenges and improve the sustainable consumption of chemotherapeutic agents. The current study presents a self-assembled, sustainable, and straightforward method for synthesizing CA nanocarriers using β-cyclodextrin conjugated graphene oxide (β-CD-GO)-functionalized Fe-based metal-organic frameworks ((β-CD-GO@MIL-100(Fe)), herein denoted as BGw-MF, through a hydrofluoric acid (HF)-free approach. The structural, functional, and morphological attributes of obtained nanocarriers were inspected through respective characterization methods. Furthermore, the CA loading efficiency (LE) was evaluated for the obtained BGw-MF nanocarriers with fixed drug concentrations, varied CA: nanocarrier ratio (w/w), and pH of the media. The results showed that BG0.5-MF had the highest LE, reaching 56.44 ± 2.25% for a 2 w/w ratio of CA in an alkaline environment (pH 9). Moreover, the CA release pattern of BG0.5-MF-CA was more controlled, with nearly 57.07 ± 2.01% release at pH 5 and 48.04 ± 1.44% at pH 7.4 over 8 days, which might enhance the therapeutic efficiency with higher release at tumor sites. The kinetics studies were subsequently conducted to evaluate the CA release characteristics of the BG0.5-MF nanocarrier. The nanocarrier followed a pseudo-second-order kinetic model for CA release at pH 5. In-vitro cytotoxicity tests of BG0.5-MF-CA revealed significant toxicity to lung cancer cells (A549) and cell viability of 68 ± 2 %, with no evident toxicity induced to normal cells (HEK293) at 400 μg/mL dose. The findings of the present work emphasized the potential of BGw-MF nanocarriers obtained at room temperature for CA-based anticancer DDS. The high loading capacity of the nanocarriers combined with the sustainable release of the drug from the nanocomposite makes it suitable for drug delivery. Moreover, the cytotoxicity of the nanocomposite towards cancer cells establishes BG0.5-MF as a promising nanocarrier for anticancer DDS.