Targeted anti-cancer therapy:Co-delivery of VEGF siRNA and Phenethyl isothiocyanate(PEITC)via cRGD-modified lipid nanoparticles for enhanced anti-angiogenic efficacy
摘要Anti-tumor angiogenesis therapy,targeting the suppression of blood vessel growth in tumors,presents a potent approach in the battle against cancer.Traditional therapies have primarily concentrated on single-target techniques,with a specific emphasis on targeting the vascular endothelial growth factor,but have not reached ideal therapeutic efficacy.In response to this issue,our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs.These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes.To enhance their targeted delivery capability,they were combined with a cyclic RGD peptide(cRGD).Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD,which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature.In this multifaceted approach,co-delivery of VEGF siRNA and phenethyl isothiocyanate(PEITC)was employed to target both tumor vascular endothelial cells and tumor cells simultaneously.The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF,inhibit the accumulation of HIF-1α under hypoxic conditions,and induce apoptosis in tumor cells.In summary,we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis,which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.
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