Delivery of a model lipophilic membrane cargo to bone marrow via cell-derived microparticles

JOURNAL OF CONTROLLED RELEASE

卷:326

Article

Yang, Chunyan^1,2  Chen, Fangfang^1,2  Ren, Ping²  Lofchy, Laren²  Wan, Chun³  Shen, Jingshi³  Wang, Guankui²  Gaikwad, Hanmant²  Ponder, Jessica⁴  Jordan, Craig T.⁴  Scheinman, Robert²  Simberg, Dmitri² 

[1] Jilin Univ, China Japan Union Hosp, Changchun, Jilin, Peoples R China

[2] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Anschutz Med Campus, Aurora, CO 80045 USA

[3] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA

[4] Univ Colorado, Sch Med, Dept Med, Div Hematol, Aurora, CO USA

关键词: Indocyanine lipid;    Liposome;    Bone marrow;    Drug delivery;    Erythrocyte;    Jurkat;    Leukemia;   

DOI  :  10.1016/j.jconrel.2020.07.019

来源: Elsevier

【 摘 要 】

Bone marrow (BM) is the central immunological organ and the origin of hematological diseases. Efficient and specific drug delivery to the BM is an unmet need. We tested delivery of fluorescent indocarbocyanine lipids (ICLs, DiR, DiD, DiI) as a model lipophilic cargo, via different carriers. Systemically injected T-lymphocyte cell line Jurkat delivered ICLs to the BM more efficiently than erythrocytes, and more selectively than PEGylated liposomes. Near infrared imaging showed that the delivery was restricted to the BM, lungs, liver and spleen, with no accumulation in the kidneys, brain, heart, intestines, fat tissue and pancreas. Following systemic injection of ICL-labeled cells in immunodeficient or immunocompetent mice, few cells arrived in the BM intact. However, between 5 and 10% of BM cells were ICL-positive. Confocal microscopy of intact BM confirmed that ICLs are delivered independently of the injected cells. Flow cytometry analysis showed that the lipid accumulated in both CD11b + and CD11b- cells, and in hematopoietic progenitors. In a xenograft model of acute myeloid leukemia, a single injection of 10 million Jurkat cells delivered DiD to similar to 15% of the tumor cells. ICL-labeled cells disappeared from blood almost immediately post-intravenous injection, but numerous cell-derived microparticles continued to circulate in blood. The microparticle particle formation was not due to the ICL labeling or complement attack and was observed after injection of both syngeneic and xenogeneic cells. Injection of microparticles produced in vitro from Jurkat cells resulted in a similar ICL delivery as the injection of intact Jurkat cells. Our results demonstrate a novel delivery paradigm wherein systemically injected cells release microparticles that accumulate in the BM. In addition, the results have important implications for studies involving systemically administered cell therapies.

【 授权许可】

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