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Issue 1, 2013
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Kinetic quantification of protein polymer nanoparticles using non-invasive imaging

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Abstract

Protein polymers are repetitive amino acid sequences that can assemble monodisperse nanoparticles with potential applications as cancer nanomedicines. Of the currently available molecular imaging methods, positron emission tomography (PET) is the most sensitive and quantitative; therefore, this work explores microPET imaging to track protein polymer nanoparticles over several days. To achieve reliable imaging, the polypeptides were modified by site-specific conjugation using a heterobifunctional sarcophagine chelator, AmBaSar, which was subsequently complexed with 64Cu. AmBaSar/64Cu was selected because it can label particles in vivo over periods of days, which is consistent with the timescales required to follow long-circulating nanotherapeutics. Using an orthotopic model of breast cancer, we observed four elastin-like polypeptides (ELPs)-based protein polymers of varying molecular weight, amino acid sequence, and nanostructure. To analyze this data, we developed a six-compartment image-driven pharmacokinetic model capable of describing their distribution within individual subjects. Surprisingly, the assembly of an ELP block copolymer (78 kD) into nanoparticles (Rh = 37.5 nm) minimally influences pharmacokinetics or tumor accumulation compared to a free ELP of similar length (74 kD). Instead, ELP molecular weight is the most important factor controlling the fate of these polymers, whereby long ELPs (74 kD) have a heart activity half-life of 8.7 hours and short ELPs (37 kD) have a half-life of 2.1 hours. These results suggest that ELP-based protein polymers may be a viable platform for the development of multifunctional therapeutic nanoparticles that can be imaged using clinical PET scanners.

Graphical abstract: Kinetic quantification of protein polymer nanoparticles using non-invasive imaging

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Publication details

The article was received on 10 Jul 2012, accepted on 03 Oct 2012 and first published on 11 Oct 2012


Article type: Paper
DOI: 10.1039/C2IB20169K
Citation: Integr. Biol., 2013,5, 183-194
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    Kinetic quantification of protein polymer nanoparticles using non-invasive imaging

    S. M. Janib, S. Liu, R. Park, M. K. Pastuszka, P. Shi, A. S. Moses, M. M. Orosco, Y.-A. Lin, H. Cui, P. S. Conti, Z. Li and J. A. MacKay, Integr. Biol., 2013, 5, 183
    DOI: 10.1039/C2IB20169K

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