Biotinylated Bilirubin Nanoparticles as a Tumor Microenvironment‐Responsive Drug Delivery System for Targeted Cancer Therapy
Abstract 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...
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| Format: | Article |
| Language: | English |
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Wiley
2018-06-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.201800017 |
| _version_ | 1797754260487667712 |
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| author | Yonghyun Lee Soyoung Lee Sangyong Jon |
| author_facet | Yonghyun Lee Soyoung Lee Sangyong Jon |
| author_sort | Yonghyun Lee |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T17:29:58Z |
| format | Article |
| id | doaj.art-bbc1c4530a9d4fd8989b8dd8f67933fd |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-12T17:29:58Z |
| publishDate | 2018-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-bbc1c4530a9d4fd8989b8dd8f67933fd2023-08-05T03:41:20ZengWileyAdvanced Science2198-38442018-06-0156n/an/a10.1002/advs.201800017Biotinylated Bilirubin Nanoparticles as a Tumor Microenvironment‐Responsive Drug Delivery System for Targeted Cancer TherapyYonghyun Lee0Soyoung Lee1Sangyong Jon2KAIST Institute for the BioCentury Department of Biological Sciences Korea Advanced Institute of Science and Technology (KAIST) 291 Daehak‐ro Daejeon 34141 Republic of KoreaKAIST Institute for the BioCentury Department of Biological Sciences Korea Advanced Institute of Science and Technology (KAIST) 291 Daehak‐ro Daejeon 34141 Republic of KoreaKAIST Institute for the BioCentury Department of Biological Sciences Korea Advanced Institute of Science and Technology (KAIST) 291 Daehak‐ro Daejeon 34141 Republic of KoreaAbstract 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.https://doi.org/10.1002/advs.201800017bilirubin nanoparticlesbiotin transportersreactive oxygen species (ROS)stimuli responsivenesstargeted cancer therapytumor microenvironments |
| spellingShingle | Yonghyun Lee Soyoung Lee Sangyong Jon Biotinylated Bilirubin Nanoparticles as a Tumor Microenvironment‐Responsive Drug Delivery System for Targeted Cancer Therapy Advanced Science bilirubin nanoparticles biotin transporters reactive oxygen species (ROS) stimuli responsiveness targeted cancer therapy tumor microenvironments |
| title | Biotinylated Bilirubin Nanoparticles as a Tumor Microenvironment‐Responsive Drug Delivery System for Targeted Cancer Therapy |
| title_full | Biotinylated Bilirubin Nanoparticles as a Tumor Microenvironment‐Responsive Drug Delivery System for Targeted Cancer Therapy |
| title_fullStr | Biotinylated Bilirubin Nanoparticles as a Tumor Microenvironment‐Responsive Drug Delivery System for Targeted Cancer Therapy |
| title_full_unstemmed | Biotinylated Bilirubin Nanoparticles as a Tumor Microenvironment‐Responsive Drug Delivery System for Targeted Cancer Therapy |
| title_short | Biotinylated Bilirubin Nanoparticles as a Tumor Microenvironment‐Responsive Drug Delivery System for Targeted Cancer Therapy |
| title_sort | biotinylated bilirubin nanoparticles as a tumor microenvironment responsive drug delivery system for targeted cancer therapy |
| topic | bilirubin nanoparticles biotin transporters reactive oxygen species (ROS) stimuli responsiveness targeted cancer therapy tumor microenvironments |
| url | https://doi.org/10.1002/advs.201800017 |
| work_keys_str_mv | AT yonghyunlee biotinylatedbilirubinnanoparticlesasatumormicroenvironmentresponsivedrugdeliverysystemfortargetedcancertherapy AT soyounglee biotinylatedbilirubinnanoparticlesasatumormicroenvironmentresponsivedrugdeliverysystemfortargetedcancertherapy AT sangyongjon biotinylatedbilirubinnanoparticlesasatumormicroenvironmentresponsivedrugdeliverysystemfortargetedcancertherapy |