Nanoparticles modified with tumor-targeting scFv deliver siRNA and miRNA for cancer therapy.
Targeted delivery of RNA-based therapeutics for cancer therapy remains a challenge. We have developed a LPH (liposome-polycation-hyaluronic acid) nanoparticle formulation modified with tumor-targeting single-chain antibody fragment (scFv) for systemic delivery of small interfering RNA (siRNA) and microRNA (miRNA) into experimental lung metastasis of murine B16F10 melanoma. The siRNAs delivered by the scFv targeted nanoparticles efficiently downregulated the target genes (c-Myc/MDM2/VEGF) in the lung metastasis. Two daily intravenous injections of the combined siRNAs in the GC4-targeted nanoparticles significantly reduced the tumor load in the lung. miRNA-34a (miR-34a) induced apoptosis, inhibited survivin expression, and downregulated MAPK pathway in B16F10 cells. miR-34a delivered by the GC4-targeted nanoparticles significantly downregulated the survivin expression in the metastatic tumor and reduced tumor load in the lung. When miR-34a and siRNAs were co-formulated in GC4-targeted nanoparticles, an enhanced anticancer effect was observed.
Chen
Yunching
Y
Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Zhu
Xiaodong
X
Zhang
Xiaoju
X
Liu
Bin
B
Huang
Leaf
L
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008175:Lung Neoplasms / Q000628:therapy*; D008545:Melanoma / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000008:administration & dosage* / Q000235:genetics / Q000502:physiology*; D053758:Nanoparticles / Q000737:chemistry*; D009362:Neoplasm Metastasis / Q000628:therapy; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000737:chemistry*; D000077022:Survivin
C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D035683:MicroRNAs; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D057127:Single-Chain Antibodies; D000077022:Survivin