PH-dependent, thermosensitive polymeric nanocarriers for drug delivery to solid tumors

Ching Yi Chen, Tae Hee Kim, Wen Chung Wu, Chi Ming Huang, Hua Wei, Christopher W. Mount, Yanqing Tian, Sei Hum Jang, Suzie H. Pun, Alex K Y Jen

    Research output: Contribution to journalArticlepeer-review

    132 Scopus citations


    Polymeric micelles are promising carriers for anti-cancer agents due to their small size, ease of assembly, and versatility for functionalization. A current challenge in the use of polymeric micelles is the sensitive balance that must be achieved between stability during prolonged blood circulation and release of active drug at the tumor site. Stimuli-responsive materials provide a mechanism for triggered drug release in the acidic tumor and intracellular microenvironments. In this work, we synthesized a series of dual pH- and temperature-responsive block copolymers containing a poly(ε-caprolactone) (PCL) hydrophobic block with a poly(triethylene glycol) block that were copolymerized with an amino acid-functionalized monomer. The block copolymers formed micellar structures in aqueous solutions. An optimized polymer that was functionalized with 6-aminocaproic acid (ACA) possessed pH-sensitive phase transitions at mildly acidic pH and body temperature. Doxorubicin-loaded micelles formed from these polymers were stable at blood pH (~7.4) and showed increased drug release at acidic pH. In addition, these micelles displayed more potent anti-cancer activity than free doxorubicin when tested in a tumor xenograft model in mice.

    Original languageEnglish (US)
    Pages (from-to)4501-4509
    Number of pages9
    Issue number18
    StatePublished - Jun 2013


    • Anti-cancer
    • PH-sensitive
    • Polymeric micelle
    • Temperature sensitive
    • Tumor delivery

    ASJC Scopus subject areas

    • Biophysics
    • Bioengineering
    • Ceramics and Composites
    • Biomaterials
    • Mechanics of Materials


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