Open AccessBiotinylated Bilirubin Nanoparticles as a Tumor Microenvironment‐Responsive Drug Delivery System for Targeted Cancer Therapy
Author(s) -
Lee Yonghyun,
Lee Soyoung,
Jon Sangyong
Publication year - 2018
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201800017
Subject(s) - hela , tumor microenvironment , biotinylation , doxorubicin , cancer research , chemistry , drug delivery , metastasis , pharmacology , cancer , cancer cell , in vitro , chemotherapy , medicine , biochemistry , tumor cells , organic chemistry
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 ≈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.