Journal
NANOSCALE
Volume 7, Issue 43, Pages 18169-18178Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c5nr05585g
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Funding
- National Natural Science Foundation of China [21273032, 81171368]
- Ph.D. Programs Foundation of Ministry of Education of China [20130075110004]
- Funds for the International Cooperation and Exchange of the National Natural Science Foundation of China [81381340177]
- Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning
- Shanghai Municipal Commission of Health and Family Planning [20134y160]
- Chinese Universities Scientific Fund [BCZD201503]
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We report the synthesis, characterization, and utilization of radioactive I-131-labeled multifunctional dendrimers for targeted single-photon emission computed tomography (SPECT) imaging and radiotherapy of tumors. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH2) were sequentially modified with 3-(4 '-hydroxyphenyl)propionic acid-OSu (HPAO) and folic acid (FA) linked with polyethylene glycol (PEG), followed by acetylation modification of the dendrimer remaining surface amines and labeling of radioactive iodine-131 1311) The generated multifunctional I-131-G5.NHAc-HPAO-PEG-FA dendrimers were characterized via different methods. We show that prior to 1311 labeling, the G5.NHAc-HPAO-PEG-FA dendrimers conjugated with approximately 9.4 HPAO moieties per dendrimer are noncytotoxic at a concentration up to 20 [LM and are able to target cancer cells overexpressing FA receptors (FAR), thanks to the modified FA ligands. In the presence of a phenol group, radioactive 1311 is able to be efficiently labeled onto the dendrimer platform with good stability and high radiochemical purity, and render the platform with an ability for targeted SPECT imaging and radiotherapy of an FAR-overexpressing xenografted tumor model in vivo. The designed strategy to use the facile dendrimer nanotechnology may be extended to develop various radioactive theranostic nanoplatforms for targeted SPECT imaging and radiotherapy of different types of cancer.
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