Preparation, characterization, and anticancer evaluation of polydatin conjugated with zinc MOF and encapsulated by liponiosomes as a potential nanotool-induce apoptosis

Abstract

Tumor is a serious worldwide issue that ranks as the second cause of mortality, regardless of the region's status. It is treated with a variety of techniques, including chemotherapy, radiotherapy, and surgery, however, there are drawbacks, such as adverse medication reactions. The investigation of stable and effective zinc metal-organic frameworks (ZMOFs) for medicinal applications has received increasing attention. Herein, we report the fabrication of our work has promised a drug delivery system (DDS) by polydatin (PD)-loaded ZMOF (PD-ZMOF) and encapsulated into liponiosomes (LNs) to form (PD-ZMOF@LNs) for increased drug targeting to tumor cells. The obtained compounds were characterized using XRD, SEM, TEM, FTIR, TGA, BET, PDI, zeta seizer, and zeta potentials (ZP) analysis. A computational approach based on Monte Carlo simulation was adopted to elucidate the PD loading mechanism into the ZMOF. Both ZMOF and PD-ZMOF@LNs showed no significant weight loss up to approximately 551⁰C, indicating their high thermal stability and the final weight decrease due to the full degradation of the ZMOF framework at that point. TEM images of ZMOF and PD-ZMOF@LNs NPs demonstrated a spherical-like and needle-like particles with an average diameter of 17.6 nm and 27.3 nm (*P < 0.05), respectively. The hydrodynamic size analyzer displayed an average particle size of 194.4 nm, with ZP of +23 mV. The encapsulation efficiency (EE), loading capacity (LC), drug release (DR), and drug-release kinetics of PD and PD-ZMOF@LNs were evaluated, and the results showed that PD was EE into ZMOF up to 91.27 ± 0.83 % (*P < 0.05). To understand the procedure of PD release at pH 6.9, four kinetic models were examined to identify which model best fit the obtained release data, and the Zero-order model demonstrated excellent release fitness with R2 = 0.9953. Anticancer activity of optimized free PD, ZMOF, and PD-ZMOF@LNs was evaluated in MCF-7 cells utilizing cell viability and flow-cytometric assays. Our samples demonstrate anti-tumor activity against MCF-7 cells with inhibitory concentrations (IC50) at 105 ± 1.5 µg/mL for PD-ZMOF@LNs. The surviving fraction and plating efficiency colony formation potential for PD-ZMOF@LNs were 32 % and 23 %, respectively (*P < 0.05). Flow cytometry analysis indicated that PD-ZMOF@LNs induced apoptosis in 77.39 % of MCF-7 cells.