A Nanoparticle Carrier for Co-Delivery of Gemcitabine and Small Interfering RNA in Pancreatic Cancer Therapy.

Abstract

BACKGROUND: The concept of precision medicine to treat cancer shows promise and a co-delivery carrier for chemotherapy drugs and target genes is the key tool for both basic research and clinical application. To address this, we developed a cancer-targeting nanoparticle vector to transfer gemcitabine (Gem) and small interfering RNA (siRNA) to pancreatic cancer. METHODS: Iron oxide nanoparticles (IONPs) resonant at 15 nm were conjugated with the single chain variable fragment (scFv) against CD44v6 (scFvCD44v6), which has proven pancreatic cancer-targeting specificity as reported in our previous study. Gem was then linked through a lysosomally cleavable tetrapeptide linker, resulting in a scFv-targeted nanoparticle construct, which was subsequently conjugated to siRNA targeting the Bmi-1 oncogene (siBmi-1) to obtain the multifunctional nanoparticle scFv-Gem-siBmi-1-NPs. A series of biological experiments were performed to test its biophysical characterization, gene silencing efficacy and anti-tumor effect in vitro and in vivo. RESULTS: The multifunctional nanoparticle not only possesses an ultra-small size of approximately 80 nm, excellent biocompatibility and biodegradability, but also exerts a synergistic anti-tumor effect both in vitro and in vivo, such as inhibition of tumor cell growth, invasion and migration, reduction of cell cycle progression and promotion of tumor apoptosis. Furthermore, this nanoparticle can efficiently target pancreatic cancer in vivo, resulting in the enhanced bioavailability and efficacy of Gem. CONCLUSION: scFv-Gem-siBmi-1-NPs provide an effective and targeted co-delivery of Gem and siBmi-1 to pancreatic cancer, and exert an efficient and corporate anti-tumor therapeutic effect. This prospective vector shows promise for precise treatment of pancreatic cancer.

• Authors: Jiajia Li, Yinting Chen, Linjuan Zeng, Guoda Lian, Shaojie Chen, Yaqing Li, Kege Yang, Kaihong Huang
• Journal: Journal of biomedical nanotechnology (J Biomed Nanotechnol) Vol. 12 Issue 8 Pg. 1654-66 (Aug 2016) ISSN: 1550-7033 [Print] United States
• PMID: 29342344 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Bmi1 protein, mouse
• CD44v6 antigen
• Hyaluronan Receptors
• Magnetite Nanoparticles
• Nanoconjugates
• Proto-Oncogene Proteins
• RNA, Small Interfering
• Deoxycytidine
• Polycomb Repressive Complex 1
• Gemcitabine

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacokinetics, pharmacology)
• Cell Line, Tumor
• Cell Physiological Phenomena (drug effects)
• Deoxycytidine (analogs & derivatives, chemistry, pharmacokinetics, pharmacology)
• Female
• Humans
• Hyaluronan Receptors
• Magnetite Nanoparticles (chemistry)
• Mice
• Mice, Inbred BALB C
• Nanoconjugates (chemistry)
• Pancreatic Neoplasms (metabolism)
• Particle Size
• Polycomb Repressive Complex 1 (genetics)
• Proto-Oncogene Proteins (genetics)
• RNA, Small Interfering (chemistry, genetics, pharmacokinetics)
• Xenograft Model Antitumor Assays
• Gemcitabine