title: Low-molecular-weight polymer-drug conjugates for synergistic anticancer activity of camptothecin and doxorubicin combinations.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California at Santa Barbara, Santa Barbara, CA 93106, USA.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Camacho
authors.affiliation: Department of Chemical & Biomolecular Engineering, Department of Biomedical Engineering, Biomanufacturing Training and Education Center (BTEC), North Carolina State University, Raleigh, NC 27695, USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Menegatti
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California at Santa Barbara, Santa Barbara, CA 93106, USA.
authors.forename: Samir
authors.initials: S
authors.lastname: Mitragotri
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols; D002166:Camptothecin / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D004357:Drug Synergism; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D008970:Molecular Weight; D009369:Neoplasms / Q000188:drug therapy*; D011108:Polymers / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry
chemical_list: D011108:Polymers; D004317:Doxorubicin; D011142:Polyvinyl Alcohol; D006820:Hyaluronic Acid; D002166:Camptothecin
keywords: combination chemotherapy; drug delivery; linker chemistry; low-molecular-weight conjugates; polymer–drug conjugates