Magnetic Drug Targeting: Preclinical in Vivo Studies, Mathematical Modeling, and Extrapolation to Humans

被引:141
作者
Al-Jamal, Khuloud T. [1 ]
Bai, Jie [1 ]
Wang, Julie Tzu-Wen [1 ]
Protti, Andrea [3 ]
Southern, Paul [4 ]
Bogart, Lara [4 ]
Heidari, Hamed [6 ]
Li, Xinjia [1 ]
Cakebread, Andrew [2 ]
Asker, Dan [1 ]
Al-Jamal, Wafa T. [5 ]
Shah, Ajay [3 ]
Bals, Sara [6 ]
Sosabowski, Jane [2 ]
Pankhurst, Quentin A. [4 ]
机构
[1] Kings Coll London, Inst Pharmaceut Sci, Fac Life Sci & Med, London SE1 9NH, England
[2] Kings Coll London, Fac Life Sci & Med, Analyt & Environm Sci Div, London SE1 9NH, England
[3] Kings Coll London, Div Cardiovasc, James Black Ctr, British Heart Fdn,Ctr Excellence, London SE5 9NU, England
[4] UCL, Healthcare Biomagnet Lab, 21 Albemarle St, London W1S 4BS, England
[5] Univ East Anglia, Sch Pharm, Norwich Res Pk, Norwich NR4 7TJ, Norfolk, England
[6] Univ Antwerp, Electron Microscopy Mat Res EMAT, Groenenborgerlaan 171, B-2020 Antwerp, Belgium
基金
英国生物技术与生命科学研究理事会;
关键词
Polymeric nanocapsules; superparamagnetic iron oxide nanoparticles; SPELT imaging; cancer therapy; nanomedicine; IRON-OXIDE NANOPARTICLES; CANCER-THERAPY; SOLID TUMORS; DELIVERY; HYDRODYNAMICS; NANOCAPSULES; BLOOD; FIELD;
D O I
10.1021/acs.nanolett.6b02261
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A sound theoretical rationale for the design of a magnetic nanocarrier capable of magnetic capture in vivo after intravenous administration could help elucidate the parameters necessary for in vivo magnetic tumor targeting. In this work, we utilized our long-circulating polymeric magnetic nano carriers, encapsulating increasing amounts of superparamagnetic iron oxide nanoparticles (SPIONs) in a biocompatible oil carrier, to study the effects of SPION loading and of applied magnetic field strength on magnetic tumor targeting in CT26 tumor-bearing mice. Under controlled conditions, the in vivo magnetic targeting was quantified and found to be directly proportional to SPION loading and magnetic field strength. Highest SPION loading, however, resulted in a reduced blood circulation time and a plateauing of the magnetic targeting. Mathematical modeling was undertaken to compute the in vivo magnetic, viscoelastic, convective, and diffusive forces acting on the nanocapsules (NCs) in accordance with the Nacev-Shapiro construct, and this was then used to extrapolate to the expected behavior in humans. The model predicted that in the latter case, the NCs and magnetic forces applied here would have been sufficient to achieve successful targeting in humans. Lastly, an in vivo murine tumor growth delay study was performed using docetaxel (DTX)-encapsulated NCs. Magnetic targeting was found to offer enhanced therapeutic efficacy, and improve mice survival compared to passive targeting at drug doses of ca. 5-8 mg, of DTX/kg. This is,, to our knowledge, the first study that truly bridges the gap between preclinical experiments and clinical translation in the field of magnetic drug targeting.
引用
收藏
页码:5652 / 5660
页数:9
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