Journal
NANOMEDICINE
Volume 11, Issue 9, Pages 1139-1151Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/nnm.16.33
Keywords
combination chemotherapy; drug delivery; linker chemistry; low-molecular-weight conjugates; polymer-drug conjugates
Funding
- University of California, Santa Barbara
- University of California, Office of the President
- NRI-MCDB Microscopy Facility
- NIH [1 S10 OD010610-01A1]
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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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