H7K(R2)2-modified pH-sensitive self-assembled nanoparticles delivering small interfering RNA targeting hepatoma-derived growth factor for malignant glioma treatment.
The lack of effective glioma therapeutics mandates the development of novel treatment strategies. Hepatoma-derived growth factor (HDGF) has been considered as a potential glioma therapeutic target, and its expression level in gliomas is positively related to the malignant grade. Although there are no effective and specific inhibitors against this target, small interfering RNA targeting HDGF (siHDGF)-mediated RNA interference (RNAi) can inhibit the target protein function by knockdown of HDGF expression. However, the application of siHDGF in glioma research and therapy is hampered by the challenge to safe and effective in vivo systemic delivery of siHDGF to gliomas. To address this question, we develop the peptide H7K(R2)2-modified pH-sensitive self-assembled hybrid nanoparticles encapsulating siHDGF (H7K(R2)2-PSNPs (siHDGF)). The acidic glioma microenvironment is beneficial to the membrane penetration of H7K(R2)2-PSNPs and the encapsulated siHDGF. Following systemic administration, H7K(R2)2-PSNPs (siHDGF) can effectively deliver siHDGF into the brain and malignant glioma cells, and therefore can significantly downregulate HDGF expression, inhibit malignant phenotypes of glioma cells, result in reduced tumor volumes and prolonged survival times in nude mice bearing U251 human glioblastoma. Thus, systemic administration of H7K(R2)2-PSNPs (siHDGF) offers an effective way for the targeted delivery of siHDGF and may serve as a practical malignant glioma therapy.
['Zhou|Meiling|M|', 'Jiang|Nan|N|', 'Fan|Junting|J|', 'Fu|Song|S|', 'Luo|Honghua|H|', 'Su|Ping|P|', 'Zhang|Mingwan|M|', 'Shi|Huihui|H|', 'Zeng|Jiaqi|J|', 'Huang|Yuan|Y|', 'Li|Yang|Y|', 'Shen|Hong|H|', 'Zhang|Aixia|A|', 'Li|Rui|R|']
D000818:Animals D001932:Brain Neoplasms D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D002470:Cell Survival D018014:Gene Transfer Techniques D005910:Glioma D006801:Humans D006863:Hydrogen-Ion Concentration D036341:Intercellular Signaling Peptides and Proteins D008819:Mice, Nude D053758:Nanoparticles D010316:Particle Size D010455:Peptides D055550:Protein Stability D034741:RNA, Small Interfering D014018:Tissue Distribution D014162:Transfection D023041:Xenograft Model Antitumor Assays
Nanoparticles Small interfering RNA Hepatoma-derived growth factor Malignant gliomas Targeted delivery