Fig. 1: Schematic illustration of facilitated gene transfection by the hybrid lipoplex with therapeutic mechanism exploration. | Nature Communications

Fig. 1: Schematic illustration of facilitated gene transfection by the hybrid lipoplex with therapeutic mechanism exploration.

From: The hybrid lipoplex induces cytoskeletal rearrangement via autophagy/RhoA signaling pathway for enhanced anticancer gene therapy

Fig. 1

The hybrid lipoplex enhances pDNA delivery through “outside-in” mechanical signaling (via the “harder” HS@Au) and “inside-out” biochemical signaling (through autophagy/RhoA pathways), inducing cytoskeletal rearrangement and promoting tumor inhibition by targeting the p53-MDM2 pathway. Once endocytosed by cells, the hybrid lipoplex (I) inhibits autophagic flux, reducing autophagosome formation and impairing lysosomal degradation of GTP-RhoA. This result in (II) increases membrane-associated GTP-RhoA and (III) enhances actin polymerization into F-actin, driving cytoskeletal rearrangement. The rearranged cytoskeleton facilitates transcytosis (IV), improving tumor penetration and accumulation of the hybrid lipoplex. Finally, (V) cytoskeletal rearrangement promotes p53 gene expression, and the co-loaded p53/SP141 hybrid lipoplex synergistically induces tumor apoptosis by targeting the p53-MDM2 pathway.

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