Image-guided and tumor-targeted drug delivery with radiolabeled unimolecular micelles.

PubMed ID: 23932288

Author(s): Guo J, Hong H, Chen G, Shi S, Zheng Q, Zhang Y, Theuer CP, Barnhart TE, Cai W, Gong S. Image-guided and tumor-targeted drug delivery with radiolabeled unimolecular micelles. Biomaterials. 2013 Nov;34(33):8323-8332. doi: 10.1016/j.biomaterials.2013.07.085. Epub 2013 Aug 8. PMID 23932288

Journal: Biomaterials, Volume 34, Issue 33, Nov 2013

Unimolecular micelles formed by dendritic amphiphilic block copolymers poly(amidoamine)-poly(L-lactide)-b-poly(ethylene glycol) conjugated with anti-CD105 monoclonal antibody (TRC105) and 1,4,7-triazacyclononane-N, N’, N-triacetic acid (NOTA, a macrocyclic chelator for (64)Cu) (abbreviated as PAMAM-PLA-b-PEG-TRC105) were synthesized and characterized. Doxorubicin (DOX), a model anti-cancer drug, was loaded into the hydrophobic core of the unimolecular micelles formed by PAMAM and PLA via physical encapsulation. The unimolecular micelles exhibited a uniform size distribution and pH-sensitive drug release behavior. TRC105-conjugated unimolecular micelles showed a CD105-associated cellular uptake in human umbilical vein endothelial cells (HUVEC) compared with non-targeted unimolecular micelles, which was further validated by cellular uptake in CD105-negative MCF-7 cells. In 4T1 murine breast tumor-bearing mice, (64)Cu-labeled targeted micelles exhibited a much higher level of tumor accumulation than (64)Cu-labeled non-targeted micelles, measured by serial non-invasive positron emission tomography (PET) imaging and confirmed by biodistribution studies. These unimolecular micelles formed by dendritic amphiphilic block copolymers that synergistically integrate passive and active tumor-targeting abilities with pH-controlled drug release and PET imaging capabilities provide the basis for future cancer theranostics.