AI Article Synopsis
- Dolastatin derivatives like monomethylauristatin E (MMAE) are used in clinical settings as antibody-drug conjugates, but their effectiveness in nanoparticle systems is not fully explored due to risks of premature drug release in the bloodstream.
- This research introduces monomethylauristatin F (MMAF) within a bombesin-tethered, reactive oxygen species (ROS)-responsive micelle system, aimed at enhancing targeted cancer therapy by improving drug delivery.
- The MMAF-loaded micelles show better cellular uptake and effective cancer cell destruction by utilizing interactions with specific receptors on cancer cells and releasing MMAF in response to ROS, indicating a promising method for delivering dolastatin drugs through nanop
Article Abstract
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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066503 | PMC |
| http://dx.doi.org/10.3390/bioengineering8040043 | DOI Listing |
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