期刊
ADVANCED SCIENCE
卷 5, 期 6, 页码 -出版社
WILEY
DOI: 10.1002/advs.201800017
关键词
bilirubin nanoparticles; biotin transporters; reactive oxygen species (ROS); stimuli responsiveness; targeted cancer therapy; tumor microenvironments
资金
- National Research Foundation of Korea (NRF) - Ministry of Science, ICT (Information and Communication Technologies)
- Global Research Laboratory [NRF-2012K1A1A2045436]
- Global Research Laboratory through National Research Foundation of Korea (NRF) - Ministry of Science, ICT (Information and Communication Technologies) [NRF-2012K1A1A2045436]
- Global Research Laboratory through National Research Foundation of Korea (NRF) - Ministry of Science, Future Planning [2012K1A1A2045436]
- National Research Foundation of Korea [2012K1A1A2045436] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
The tumor microenvironment (TME) plays a crucial role in tumorigenesis and cancer cell metastasis. Accordingly, a drug-delivery system (DDS) that is capable of targeting tumor and releasing drugs in response to TME-associated stimuli should lead to potent antitumor efficacy. Here, a cancer targeting, reactive oxygen species (ROS)-responsive drug delivery vehicle as an example of a TME-targeting DDS is reported. Tumor targeting is achieved using biotin as a ligand for biotin transporter-overexpressing malignant tumors, and bilirubin-based nanoparticles (BRNPs) are used as a drug-delivery carrier that enables ROS-responsive drug release. Doxorubicin-loaded, biotinylated BRNPs (Dox@bt-BRNPs) with size of approximate to 100 nm are prepared by a one-step self-assembly process. Dox@bt-BRNPs exhibit accelerated Dox-release behavior in response to ROS and show specific binding as well as anticancer activity against biotin transporter-overexpressing HeLa cells in vitro. bt-BRNPs labeled with cypate, near-infrared dye, show much greater accumulation at tumor sites in HeLa tumor-bearing mice than BRNPs lacking the biotin ligand. Finally, intravenous injection of Dox@bt-BRNPs into HeLa tumor-bearing mice results in greater antitumor efficacy compared with free Dox, bt-BRNPs only, and Dox@BRNPs without causing any appreciable body weight loss. Collectively, these findings suggest that bt-BRNPs hold potential as a new TME-responsive DDS for effectively treating various tumors.
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