Chitosan‐Conjugated Folic Acid–Functionalized Zn‐MOF Nanocarrier for pH‐Responsive Targeted Capecitabine Delivery in Hepatocellular Carcinoma
Ali Junaid, Faiqa Noreen, Hamada H. Amer, Aiysha Althobaiti, Zeinhom M. El‐Bahy, Faizullah Khan, Magdi E. A. Zaki, Sobhi M. Gomha, Muhammad Naeem Ashiq, Zahid ShafiqABSTRACT
A multifunctional metal–organic framework (MOF) nanocarrier designated CA/Zn‐MOF/FC is reported for the pH‐responsive, receptor‐targeted delivery of capecitabine (CA) against hepatocellular carcinoma (HCC). The nanoplatform is constructed from a self‐assembled, pillared‐layer Zn 2 (BDC) 2 (DABCO) scaffold in which terephthalate (BDC) and 1,4‐diazabicyclo[2.2.2]octane (DABCO) act as linkers bridging Zn 2+ coordination nodes, affording an exceptionally high volumetric drug‐loading capacity. Dual functionalization with chitosan and folic acid (FC) is designed to confer active‐targeting functionality: Chitosan is intended to facilitate macropinocytosis and endosomal escape, whereas folic acid is proposed to direct folate receptor–mediated uptake by engaging folate receptors reported to be overexpressed on HepG 2 HCC cells. These results support CA/Zn‐MOF/FC as a stimulus‐responsive MOF nanoplatform with proposed receptor‐targeting functionality and promising in vitro performance, warranting further in vivo evaluation to establish its potential for HCC chemotherapy. In vitro cytotoxicity assays demonstrate that CA/Zn‐MOF/FC achieves an IC 50 of 21.3 ± 0.2 μM and 77.12% growth inhibition against HepG 2 cells, outperforming free CA (IC 50 : 24.1 ± 0.5 μM; 68.91% inhibition) and CA/Zn‐MOF, whereas LO 2 normal cell viability remained above 84% across all formulations, confirming substantially elevated tumor selectivity. These results support CA/Zn‐MOF/FC as a stimulus‐responsive MOF nanoplatform with proposed receptor‐targeting functionality and significant promise for HCC chemotherapy.