Bombesin-Tethered Reactive Oxygen Species (ROS)-Responsive Nanoparticles for Monomethyl Auristatin F (MMAF) Delivery
Dolastatin derivatives, represented by monomethylauristatin E (MMAE), have been translated in clinic with a form of antibody–drug conjugate; however, their potential in nanoparticle systems has not been well established due to the potential risk of immature release of extremely high cytotoxic dolast...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-03-01
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| Series: | Bioengineering |
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| Online Access: | https://www.mdpi.com/2306-5354/8/4/43 |
| _version_ | 1797539703152443392 |
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| author | Jihoon Kim Jee Seon Kim Kyung Hyun Min Young-Hwa Kim Xiaoyuan Chen |
| author_facet | Jihoon Kim Jee Seon Kim Kyung Hyun Min Young-Hwa Kim Xiaoyuan Chen |
| author_sort | Jihoon Kim |
| collection | DOAJ |
| description | Dolastatin derivatives, represented by monomethylauristatin E (MMAE), have been translated in clinic with a form of antibody–drug conjugate; however, their potential in nanoparticle systems has not been well established due to the potential risk of immature release of extremely high cytotoxic dolastatin drugs during blood circulation. Herein, we rationally propose monomethylauristatin F (MMAF), a dolastatin-derived, loaded nanoparticle system composed of bombesin (BBN)-tethered ROS-responsive micelle system (BBN-PEG-PPADT) to achieve efficient anticancer therapy with targeted and efficient delivery of MMAF. The developed MMAF-loaded BBN-PEG-PPADT micelles (MMAF@BBN-PEG-PPADT) exhibited improved cellular uptake via interactions between BBN and gastrin-releasing peptide receptors on the cancer cells and the intracellular burst release of MMAF, owing to the ROS-responsive disruption, which allowed the efficient anticancer effects of MMAF in vitro. This study suggests the potential of nanoparticle systems in the delivery of dolastatin drugs. |
| first_indexed | 2024-03-10T12:49:36Z |
| format | Article |
| id | doaj.art-b9fb317cd87d49f383b31ccefd17b2ad |
| institution | Directory Open Access Journal |
| issn | 2306-5354 |
| language | English |
| last_indexed | 2024-03-10T12:49:36Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Bioengineering |
| spelling | doaj.art-b9fb317cd87d49f383b31ccefd17b2ad2023-11-21T13:13:34ZengMDPI AGBioengineering2306-53542021-03-01844310.3390/bioengineering8040043Bombesin-Tethered Reactive Oxygen Species (ROS)-Responsive Nanoparticles for Monomethyl Auristatin F (MMAF) DeliveryJihoon Kim0Jee Seon Kim1Kyung Hyun Min2Young-Hwa Kim3Xiaoyuan Chen4Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr NW, Atlanta, GA 30332, USALG Chem, Seoul 07336, KoreaDepartment of Pharmacy, School of Pharmacy, Jeonbuk National University, Jeonju 54896, KoreaMechanical Design Engineering, Jeonbuk National University, Jeonju 54896, KoreaYong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore 117597, SingaporeDolastatin derivatives, represented by monomethylauristatin E (MMAE), have been translated in clinic with a form of antibody–drug conjugate; however, their potential in nanoparticle systems has not been well established due to the potential risk of immature release of extremely high cytotoxic dolastatin drugs during blood circulation. Herein, we rationally propose monomethylauristatin F (MMAF), a dolastatin-derived, loaded nanoparticle system composed of bombesin (BBN)-tethered ROS-responsive micelle system (BBN-PEG-PPADT) to achieve efficient anticancer therapy with targeted and efficient delivery of MMAF. The developed MMAF-loaded BBN-PEG-PPADT micelles (MMAF@BBN-PEG-PPADT) exhibited improved cellular uptake via interactions between BBN and gastrin-releasing peptide receptors on the cancer cells and the intracellular burst release of MMAF, owing to the ROS-responsive disruption, which allowed the efficient anticancer effects of MMAF in vitro. This study suggests the potential of nanoparticle systems in the delivery of dolastatin drugs.https://www.mdpi.com/2306-5354/8/4/43auristatin drugsMMAFbombesinreactive oxygen species-responsivedrug delivery |
| spellingShingle | Jihoon Kim Jee Seon Kim Kyung Hyun Min Young-Hwa Kim Xiaoyuan Chen Bombesin-Tethered Reactive Oxygen Species (ROS)-Responsive Nanoparticles for Monomethyl Auristatin F (MMAF) Delivery Bioengineering auristatin drugs MMAF bombesin reactive oxygen species-responsive drug delivery |
| title | Bombesin-Tethered Reactive Oxygen Species (ROS)-Responsive Nanoparticles for Monomethyl Auristatin F (MMAF) Delivery |
| title_full | Bombesin-Tethered Reactive Oxygen Species (ROS)-Responsive Nanoparticles for Monomethyl Auristatin F (MMAF) Delivery |
| title_fullStr | Bombesin-Tethered Reactive Oxygen Species (ROS)-Responsive Nanoparticles for Monomethyl Auristatin F (MMAF) Delivery |
| title_full_unstemmed | Bombesin-Tethered Reactive Oxygen Species (ROS)-Responsive Nanoparticles for Monomethyl Auristatin F (MMAF) Delivery |
| title_short | Bombesin-Tethered Reactive Oxygen Species (ROS)-Responsive Nanoparticles for Monomethyl Auristatin F (MMAF) Delivery |
| title_sort | bombesin tethered reactive oxygen species ros responsive nanoparticles for monomethyl auristatin f mmaf delivery |
| topic | auristatin drugs MMAF bombesin reactive oxygen species-responsive drug delivery |
| url | https://www.mdpi.com/2306-5354/8/4/43 |
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