NIR-emissive PEG-b-TCL micelles for breast tumor imaging and minimally invasive pharmacokinetic analysis

被引：16

作者：

Hofmann, Christina L. ^{[1
]}

O'Sullivan, Melanie C. ^{[2
]}

Detappe, Alexandre ^{[3
,4
,5
]}

Yu, Yingjie ^{[5
]}

Yang, Xi ^{[5
]}

Qi, Wei ^{[2
]}

Landon, Chelsea D. ^{[6
]}

Therien, Michael J. ^{[2
]}

Dewhirst, Mark W. ^{[1
,6
,7
]}

Ghoroghchian, P. Peter ^{[3
,4
,5
]}

Palmer, Gregory M. ^{[7
]}

机构：

[1] Duke Univ, Dept Biomed Engn, Room 136 Hudson Hall, Durham, NC 27708 USA

[2] Duke Univ, Dept Chem, French Family Sci Ctr, 124 Sci Dr, Durham, NC 27708 USA

[3] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA

[4] Harvard Med Sch, 25 Shattuck St, Boston, MA 02115 USA

[5] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave,Room 76-261F, Cambridge, MA 02139 USA

[6] Duke Univ, Med Ctr, Dept Pathol, Box 3455, Durham, NC 27710 USA

[7] Duke Univ, Med Ctr, Radiat Oncol Dept, Box 3455, Durham, NC 27710 USA

来源：

NANOSCALE | 2017年 / 9卷 / 36期

基金：

美国国家卫生研究院;

关键词：

RADIATION-THERAPY; GUIDED SURGERY; POLYMERSOMES; NANOPARTICLES; FLUOROPHORES; VESICLES; LIPOSOMES; TOXICITY; MOUSE;

D O I：

10.1039/c7nr02363d

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Motivated by the goal of developing a fully biodegradable optical contrast agent with translational clinical potential, a nanoparticle delivery vehicle was generated from the self-assembly of poly(ethylene-glycol)-block-poly(trimethylene carbonate-co-caprolactone) (PEG-b-TCL) copolymers. Cryogenic transmission electron microscopy verified that PEG-b-TCL-based micelles were formed at low solution temperatures (similar to 38 degrees C). Detailed spectroscopic experiments validated facile loading of large quantities of the high emission dipole strength, tris(porphyrin)-based fluorophore PZn3 within their cores, and the micelles displayed negligible in vitro and in vivo toxicities in model systems. The pharmacokinetics and biodistribution of PZn3-loaded PEG-b-TCL-based micelles injected intravenously were determined via ex vivo near-infrared (NIR) imaging of PZn3 emission in microcapillary tubes containing minute quantities of blood, to establish a novel method for minimally invasive pharmacokinetic monitoring. The in vivo circulatory half-life of the PEG-b-TCL-based micelles was found to be similar to 19.6 h. Additionally, longitudinal in vivo imaging of orthotopically transplanted breast tumors enabled determination of micelle biodistribution that correlated to ex vivo imaging results, demonstrating accumulation predominantly within the tumors and livers of mice. The PEG-b-TCL-based micelles quickly extravasated within 4T1 orthotopic mammary carcinomas, exhibiting peak accumulation at similar to 48 h following intravenous tail-vein injection. In summary, PEG-b-TCL-based micelles demonstrated favorable characteristics for further development as in vivo optical contrast agents for minimally invasive imaging of breast tumors.

引用

页码：13465 / 13476

页数：12

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