期刊
ACS NANO
卷 8, 期 5, 页码 4530-4538出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn406632u
关键词
hollow gold nanospheres; SPECT/CT; biodistribution; epidermal growth factor receptor; head and neck cancer; aptamer
类别
资金
- National Institutes of Health [U54CA151668]
- Odyssey Fellowship
- SPORE Head and Neck Career Development Award
- John S. Dunn Foundation
- National Institutes of Health (EUREKA) [1-R01-GM094933]
- Welch Foundation [F-1654]
- National Security Science and Engineering Faculty Fellowship [FA9550-10-1-0169]
The purpose of this study was to compare the binding affinity and selective targeting of aptamer- and antibody-coated hollow gold nanospheres (HAuNS) targeted to epidermal growth factor receptors (EGFR). EGFR-targeting aptamers were conjugated to HAuNS (apt-HAuNS) by attaching a thiol-terminated single-stranded DNA to the HAuNS and then adding the complementary RNA targeted to EGFR. Apt-HAuNS was characterized in terms of size, surface charge, absorption, and number of aptamers per particle. The in vivo pharmacokinetics, in vivo biodistribution, and micro-SPECT/CT imaging of In-111-labeled apt-HAuNS and anti-EGFR antibody (C225)-conjugated HAuNS were evaluated in nude mice bearing highly malignant human OSC-19 oral tumors. In-111-labeled PEG-HAuNS was used as a control (n = 5/group). Apt-HAuNS did not have an altered absorbance profile or size (lambda(max) = 800 nm; diameter = 55 nm) compared to C225-HAuNS or PEG-HAuNS. The surface charge became more negative upon conjugation of the aptamer (-51.4 vs -19.0 for PEG-HAuNS and -25.0 for C225-HAuNS). The number of aptamers/particle was similar to 250. In vitro cell binding and in vivo biodistribution showed selective binding of the apt-HAuNS to EGFR. mu SPECT/CT imaging confirmed that there was more tumor uptake of apt-HAuNS than C225-HAuNS. Aptamer is a promising ligand for image-guided delivery of nanoparticles for treatment of tumor cells overexpressing EGFR.
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