Delivery of siRNA using hyaluronic acid‐guided nanoparticles for downregulation of CXCR4

Abstract

AbstractIn this study, effective transport of small interfering RNAs (siRNAs) via hyaluronic acid (HA) receptor was carried out with biodegradable HA and low‐molecular weight polyethyleneimine (PEI)‐based transport systems. Gold nanoparticles (AuNPs) capable of giving photothermal response, and their conjugates with PEI and HA, were also added to the structure. Thus, a combination of gene silencing, photothermal therapy and chemotherapy, has been accomplished. The synthesized transport systems ranged in size, between 25 and 690 nm. When the particles were applied at a concentration of 100 μg mL−1 (except AuPEI NPs) in vitro, cell viability was above 50%. Applying radiation after the conjugate/siRNA complex (especially those containing AuNP) treatment, increased the cytotoxic effect (decrease in cell viability of 37%, 54%, 13%, and 15% for AuNP, AuPEI NP, AuPEI‐HA, and AuPEI‐HA‐DOX, respectively) on the MDA‐MB‐231 cell line. CXCR4 gene silencing via the synthesized complexes, especially AuPEI‐HA‐DOX/siRNA was more efficient in MDA‐MB‐231 cells (25‐fold decrease in gene expression) than in CAPAN‐1 cells. All these results demonstrated that the synthesized PEI‐HA and AuPEI‐HA‐DOX conjugates can be used as siRNA carriers that are particularly effective, especially in the treatment of breast cancer.