A cationic amino acid polymer nanocarrier synthesized in supercritical CO₂ for co-delivery of drug and gene to cervical cancer cells

The present study was undertaken to investigate the ability of a drug curcumin-loaded polymer to inhibit the growth of cervical cancer cells by enhancing the anti-cancer efficiency of curcumin. We synthesized poly(methacryloyl beta-alanine) (PMBA) as a nanocarrier by radical polymerization in supercritical CO₂. The results showed that the curcumin encapsulated and folic acid (FA)-treated PMBA (Poly@Cur-FA) for 24 h activated the reactive oxygen species-mediated programmed cell death machinery in HeLa cells. This remarkable effect of Poly@Cur-FA treatment was visualized using different fluorescent probes, which demonstrated that the Poly@Cur-FA treatment disrupted the cell membrane, as also supported by scanning electron microscopy observations. The effect of Poly@Cur-FA dispersion on the cells was observed under a transmission electron microscope. Further, the HeLa cells were treated with the polymer encapsulated curcumin and Bcl2 siRNA (Pol-Cur-siRNA) for 24 h, which effectively suppressed the Bcl2 and simulated the autophagic pathway. This co-delivery system was designed to inhibit curcumin efflux and can enhance the treatment efficacy by targeting multiple signaling pathways, including cell cycle, apoptotic, and autophagic pathways. Collectively, the Pol-Cur-siRNA system appears to offer an efficient combinational therapeutic strategy that might overcome the problems associated with the chemosensitivity against the standard synthetic anti-cancer drugs. To support the experimental data, an artificial neural network model was developed to foresee the drug and gene release behaviors.