Porous polymersomes with encapsulated Gd-labeled dendrimers as highly efficient MRI contrast agents

Zhiliang Cheng, Daniel L.J. Thorek, Andrew Tsourkas

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

The use of nanovesicles with encapsulated Gd as magnetic resonance (MR) contrast agents has largely been ignored due to the detrimental effects of the slow water exchange rate through the vesicle bilayer on the relaxivity of encapsulated Gd. Here, the facile synthesis of a composite MR contrast platform is described; it consists of dendrimer conjugates encapsulated in porous polymersomes. These nanoparticles exhibit improved permeability to water flux and a large capacity to store chelated Gd within the aqueous lumen, resulting in enhanced longitudinal relaxivity. The porous polymersomes, ∼130nm in diameter, are produced through the aqueous assembly of the polymers, polyethylene oxide-b-polybutadiene (PBdEO), and polyethylene oxide-b-polycaprolactone (PEOCL), Subsequent hydrolysis of the caprolactone (CL) block resulted in a highly permeable outer membrane. To prevent the leakage of small Gd-chelate through the pores, Gd was conjugated to polyamidoamine (PAMAM, dendrimers via diethylenetriaminepentaacetic acid dianhydride (DTPA dianhydride) prior to encapsulation. As a result of the slower rotational correlation time of Gd-labeled dendrimers, the porous outer membrane of the nanovesicle, and the high Gd paybad, these functional nanoparticles are found to exhibit a relaxivity (R1) of 292 109 mM-1 s-1 per particle. The polymersomes are also found to exhibit unique pharmacokinetics with a circulation half-life of >3.5 h and predominantly renal clearance.

Original languageEnglish
Pages (from-to)3753-3759
Number of pages7
JournalAdvanced Functional Materials
Volume19
Issue number23
DOIs
StatePublished - Sep 12 2009

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