Low-molecular-weight polymer–drug conjugates for synergistic anticancer activity of camptothecin and doxorubicin combinations. (May 2016)

• Record Type: Journal Article
• Authors: Camacho, Kathryn M; Menegatti, Stefano; Mitragotri, Samir
• Is Part Of: Nanomedicine. Volume 11:Number 9(2016)
• Page Start: 1139
• Page End: 1151
• Publication Date: 2016-05
• Subjects: combination chemotherapy -- drug delivery -- linker chemistry -- low-molecular-weight conjugates -- polymer–drug conjugates; Nanotechnology -- Periodicals; Medical technology -- Periodicals; Nanotechnology -- Therapeutic use -- Periodicals; 610.28
• DOI: 10.2217/nnm.16.33
• Languages: English
• ISSNs: 1743-5889

Abstract

Background: High-molecular-weight (MW) polymers (>50, 000 Da) can be conjugated to chemotherapy drugs in order to improve their tumor accumulation, while low MW polymers ≤10, 000 Da are often overlooked due to faster plasma clearance. Small polymers, however, may facilitate deeper tumor penetration.Materials & methods: Here, we investigate the anticancer efficacy of 10 kDa hyaluronic acid or poly(vinyl alcohol) conjugated to synergistic combinations of camptothecin and doxorubicin, with emphasis on chemical linker impacts.Results: Our results emphasize drug hydrolyzability for synergy preservation, and also demonstrate superior cancer cell inhibition with low MW polymer–drug conjugates.Conclusion: This study shows the high therapeutic potential of low MW polymer–drug conjugates for polychemotherapy delivery, and provides further insight into the development of polymer-drug therapeutics.