Tumor-Specific Monomethyl Auristatin E (MMAE) Prodrug Nanoparticles for Safe and Effective Chemotherapy
- 주제(키워드) prodrug , monomethyl auristatin E , nanoparticle , targeted therapy , chemotherapy
- 주제(기타) Pharmacology & Pharmacy
- 설명문(일반) [Cho, Hanhee; Ahn, Cheol-Hee] Seoul Natl Univ, Dept Mat Sci & Engn, Seoul 08826, South Korea; [Cho, Hanhee; Shim, Man Kyu; Moon, Yujeong; Song, Sukyung; Kim, Jinseong; Choi, Jiwoong; Kim, Jeongrae; Lee, Youngjoo; Yoon, Hong Yeol] Korea Inst Sci & Technol KIST, Biomed Res Div, Seoul 02792, South Korea; [Kim, Jinseong; Choi, Jiwoong; Kim, Jeongrae; Lee, Youngjoo; Park, Jung Yeon; Kim, Yongju] Korea Univ, KU KIST Grad Sch Converging Sci & Technol, Seoul 02841, South Korea; [Park, Jung Yeon; Kim, Yongju] Korea Univ, KU KIST Grad Sch Converging Sci & Technol, Dept Integrat Energy Engn, Seoul 02841, South Korea; [Kim, Mi Ra] Inje Univ, Haeundae Paik Hosp, Coll Med, Dept Otorhinolaryngol Head & Neck Surg, Busan 48108, South Korea; [Kim, Kwangmeyung] Ewha Womans Univ, Coll Pharm, Grad Sch Pharmaceut Sci, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published
- 발행기관 MDPI
- 발행년도 2022
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000203062
- 본문언어 영어
- Published As https://doi.org/10.3390/pharmaceutics14102131
- PubMed https://pubmed.ncbi.nlm.nih.gov/36297566
초록/요약
A prodrug is bioreversible medication that is specifically converted to the active drugs by enzymes overexpressed in the tumor microenvironment, which can considerably reduce the chemotherapy-induced side effects. However, prodrug strategies usually have low antitumor efficacy compared to free drugs by delayed drug release. This is because they need time to be activated by enzymatic cleavage and they also cannot be fully recovered to the active drugs. Therefore, highly potent anticancer drug should be considered to expect a sufficient antitumor efficacy. Herein, we propose tumor-specific monomethyl auristatin E (MMAE) prodrug nanoparticles for safe and effective chemotherapy. The cathepsin B-specific cleavable FRRG peptide and MMAE are chemically conjugated via one-step simple synthetic chemistry. The resulting FRRG-MMAE molecules form stable nanoparticles without any additional carrier materials by hydrophobic interaction-derived aggregations. The FRRG-MMAE nanoparticles efficiently accumulate within the tumor tissues owing to the enhanced permeability and retention (EPR) effect and inhibit the tubulin polymerization by releasing free MMAE in the cathepsin B-overexpressed tumor cells. In contrast, FRRG-MMAE nanoparticles maintain a non-toxic inactive state in the normal tissues owing to innately low cathepsin B expression, thereby reducing MMAE-related severe toxicity. Collectively, this study provides a promising approach for safe and effective chemotherapy via MMAE-based prodrug nanoparticles, which may open new avenues for advanced drug design for translational nanomedicine.
more