Precise drug delivery for heart disease and cancer-- Monocytes count.
Aptamer-modified nanoparticles hitchhikes circulating monocytes to achieve precise drug delivery to cardiac infarct site and tumor.
One of the major challenges in modern pharmacological treatment is the difficulty to precisely deliver the drugs to the sites for treatment. Dr. Patrick C.H. Hsieh, the lead author and a distinguished research fellow at the Institute of Biomedical Sciences (IBMS), Academia Sinica (AS) and his research team established a novel drug delivery system in which the aptamer-modified liponanoparticles target to the circulating monocytes and travel along with the monocytes to the injury sites.
After injury, the number of monocytes, a type of white blood cells, increases in the circulation and monocytes move to the injury sites to remove the damaged cells. This new drug-delivery system takes advantages of the recruitment of monocytes to the injury sites by targeting the drug-loaded liposomes to the circulating monocytes via monocyte-specific aptamers, synthetic oligonucleotides that bind to a specific target molecule, on the surface of the particles. The circulating monocytes then carry these aptamer-drug-liposomes to the injury sites where the drugs are released.
Dr. Hsieh’s team used a technology called Cell-Systematic Evolution of Ligands by Exponential Enrichment (Cell-SELEX) to select a monocyte-specific aptamer from the oligonucleotide library of more than a quadrillion (1015) sequences. The aptamer can be easily modified on the liposomes. The aptamer-liposomes are stable and can be loaded with various drugs of interests.
The research team applied the aptamer- -liponanoparticles which are conjugated with a cardio-protective drug called IOX2 to amouse cardiac ischemia/reperfusion (I/R) model and found a significantly increased drug loading in the infarct area. The team observed reduced cardiomyocyte death, increased vessel growth and improved lifespan in the mouse I/R model.
Dr. Hsieh’s team also applied this novel drug delivery system to deliver gemcitabine, an anti-cancer compound, to the tumor site in a mouse pancreatic cancer model. After intravenous injection, more gemcitabine accumulated in the tumor, leading to augmentation of tumor cell death, shrinkage of tumor size, and an improved survival rate of the mice.
The team also suggests that the benefits of using this immune cell shuttling drug delivery system include the monocyte-navigating specificity of the aptamer, the stability of the aptamer-liposomes and the feasibility of encapsulating drugs with various purses.
The study entitled “Immune cell shuttle for precise delivery of nanotherapeutics for heart disease and cancer” was published online in Science Advances on 23th of April. The research team is led by Dr. Patrick Hsieh at IBMS, in collaboration with Dr. Hsien-Ming Lee at the Institute of Chemistry, AS; Dr. Peilin Chen at the Research Center for Applied Sciences, AS; Dr. Yun-Wen Tien at the Surgery Department of National Taiwan University Hospital; Dr. Timothy J. Kamp at The Department of Medicine and The Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison; Dr. James Lai at the Department of Bioengineering, University of Washington in Seattle. The study is funded by the AS Thematic Program.
Dr. Patrick C.H. Hsieh, Research Fellow in Institute of Biomedical Sciences, Academia Sinica
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Miss Pei-Ling Chen, Administrative Office, Institute of Biomedical Sciences, Academia Sinica
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