Research Article

Low-molecular-weight polymer–drug conjugates for synergistic anticancer activity of camptothecin and doxorubicin combinations

Department of Chemical Engineering, Center for Bioengineering, University of California at Santa Barbara, Santa Barbara, CA 93106, USA

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Stefano Menegatti

Department of Chemical & Biomolecular Engineering, Department of Biomedical Engineering, Biomanufacturing Training and Education Center (BTEC), North Carolina State University, Raleigh, NC 27695, USA

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Samir Mitragotri

*Author for correspondence:

E-mail Address: samir@engineering.ucsb.edu

Department of Chemical Engineering, Center for Bioengineering, University of California at Santa Barbara, Santa Barbara, CA 93106, USA

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Published Online:15 Apr 2016https://doi.org/10.2217/nnm.16.33

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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.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 11, No. 9

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Published online 15 April 2016

Published in print May 2016

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Financial & competing interests disclosure

The authors would like to acknowledge the use of the Biological Nanostructures Laboratory within the California NanoSystems Institute, supported by the University of California, Santa Barbara and the University of California, Office of the President, as well as the NRI-MCDB Microscopy Facility, funded by NIH grant no. 1 S10 OD010610-01A1. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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