PEGylated Chitosan-Albumin Nanocomposite for Efficient siRNA Delivery Against Lung Cancer

Background: The utilization of siRNA therapeutics in cancer treatment offers significant potential; however, the targeted delivery of siRNAs to tumor cells remains a major challenge. This study presents a novel folate-targeted PLGA–PEG-stabilized chitosan–albumin nanocomposite (FA-PPC-siRNA) designed for efficient siRNA delivery to cancer cells. Methods: The physicochemical properties of FA-PPC-siRNA were characterized, and its encapsulation efficiency, release profile, cellular uptake and antitumor effects were evaluated in vitro and in vivo. Results: The average particle size of FA-PPC-siRNA was (186.62 ± 8.93) nm and the zeta potential was (23.61 ± 3.93) mV. The encapsulation efficiency reached (96.28 ± 4.5)%. Over a 24-h period, the cumulative siRNA release rate was (93.62 ± 3.48)%, showing a pH-dependent release pattern. FA-PPC-siRNA demonstrated effective targeting and uptake by lung cancer cells, along with low cytotoxicity. It significantly inhibited the proliferation of lung cancer cells and exhibited excellent biocompatibility and tumor suppression in vivo. Conclusions: The FA-PPC-siRNA developed in this study exhibits lung cancer cell targeting capabilities and controlled drug release properties, facilitating efficient siRNA delivery and antitumor effects. This innovative nanocomposite shows promising potential for siRNA-based tumor-targeted drug delivery.