Image-guided and tumor-targeted drug delivery with radiolabeled unimolecular micelles.
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.
School of Chemical Engineering, Tianjin University, Tianjin 300072, China.|Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.|Wisconsin Institutes for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.
Jintang
J
Guo
Department of Radiology, University of Wisconsin-Madison, Madison, WI 53705, USA.|Department of Medical Physics, University of Wisconsin-Madison, Madison, WI 53705, USA.
Hao
H
Hong
Wisconsin Institutes for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.|Materials Science Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
Guojun
G
Chen
Department of Radiology, University of Wisconsin-Madison, Madison, WI 53705, USA.|Materials Science Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
Sixiang
S
Shi
Wisconsin Institutes for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.|Materials Science Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
Qifeng
Q
Zheng
Department of Medical Physics, University of Wisconsin-Madison, Madison, WI 53705, USA.
Yin
Y
Zhang
TRACON Pharmaceuticals, Inc., San Diego, CA, USA.
Charles P
CP
Theuer
Department of Medical Physics, University of Wisconsin-Madison, Madison, WI 53705, USA.
Todd E
TE
Barnhart
Department of Radiology, University of Wisconsin-Madison, Madison, WI 53705, USA.|Department of Medical Physics, University of Wisconsin-Madison, Madison, WI 53705, USA.|Materials Science Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
Weibo
W
Cai
Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.|Wisconsin Institutes for Discovery, University of Wisconsin-Madison, Madison, WI 53715, USA.|Materials Science Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
Shaoqin
S
Gong
D000818:Animals; D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D000071063:Endoglin; D005260:Female; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D049268:Positron-Emission Tomography; D011956:Receptors, Cell Surface; D017550:Spectroscopy, Fourier Transform Infrared
D015703:Antigens, CD; D000970:Antineoplastic Agents; C064206:ENG protein, human; D000071063:Endoglin; D008823:Micelles; D011956:Receptors, Cell Surface
CD105 (endoglin); Dendritic amphiphilic block copolymer; Molecular imaging; Nanocarriers; Positron emission tomography (PET); Unimolecular micelles