Facile one-step synthesis of NIR-Responsive siRNA-Inorganic hybrid nanoplatform for imaging-guided photothermal and gene synergistic therapy

Diagnosis-guided synergistic treatment based on innovative nanomaterials is of great significance for the development of anti-cancer therapies. However, the low delivery efficiency of therapeutic gene and the inability to trigger release on demand are still major obstacles impeding its wide application. Herein, we report an ultra-fast one-step method within 2 min to prepare a smart carrier, liposome-coated Prussian blue @ gold nano-flower, which is named LPAR after linking with tumor-targeting peptide. The versatile LPAR not only can respond to near-infrared (NIR) light, achieve the selective delivery and the controlled release of siRNA targeting the mutant gene of Kras at its codon-12 from Glycine (G) to Aspartic acid (D) (named as G12D mutant gene) in the malignant pancreatic tumors, but also efficiently convert the absorbed NIR light into the heat to realize gene-photothermal synergistic therapy both in vitro and in vivo. Theoretical simulation results reveal that the outstanding photothermal conversion efficiency of LPAR is mainly due to its higher electric field intensity and power density distributions. Furthermore, the LPAR possesses the capabilities for triple-modal imaging. Therefore, the developed NIR light-responsive LPAR has the potential to be served as a tumor-targeted nano-delivery system for imaging-guided synergistic therapy of cancers.