期刊
MOLECULAR PHARMACEUTICS
卷 10, 期 1, 页码 11-17出版社
AMER CHEMICAL SOC
DOI: 10.1021/mp300208g
关键词
viral capsid; VLP; bacteriophage P22; magnetic resonance imaging; MRI; imaging agent; contrast agent; T1; relaxivity; gadolinium; DTPA-Gd; azide-alkyne click chemistry; nanoparticle; nanocomposite; protein cages; payload
资金
- National Institutes of Health [R01-EB012027]
Attachment of multiple chelated Gd3+ ions to the interior of bacteriophage P22 viral capsids affords nanoscale MRI contrast agents with extremely high relaxivity values. Highly fenestrated wiffleball morphology is unique to P22 and assures water exchange between the environment and interior cavity of the capsid. The cavity of P22 wiffleball was functionalized with a branched oligomer comprising multiple DTPA-Gd complexes resulting in an impressive payload of 1,900 Gd3+ ions inside each 64 nm capsid. High relaxivities of r(l,ionic) = 21.7 mM(-1) s(-1) and r(l,particle) = 41,300 mM(-1) s(-1) at 298 K, 0.65 T (28 MHz) are reported, with r(1)/r(2) ratio of 0.80 and optimized rotational correlation time for this system. Specific design modifications are suggested for future improvements of viral capsid-based MRI contrast agents directed toward clinical translation.
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