A highly tumor-specific light-triggerable drug carrier responds to hypoxic tumor conditions for effective tumor treatment. (January 2016)

• Record Type: Journal Article
• Authors: Park, Wooram; Bae, Byoung-chan; Na, Kun
• Is Part Of: Biomaterials. Volume 77(2016)
• Page Start: 227
• Page End: 234
• Publication Date: 2016-01
• Subjects: Tumor treatment -- Light-triggered -- Drug delivery -- Tumor hypoxia -- Photosensitizer; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2015.11.014
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Light-triggered drug delivery is among the most investigated stimulus-response strategies and has been widely explored in cancer treatment. However, the limited specificity of light-triggered drug delivery reduces the therapeutic efficacy and causes considerable undesirable side effects. In this work, we demonstrate a highly tumor-specific light-triggerable drug carrier (H–LTDC) induced by a combination of internal (i.e., tumor hypoxia) and external stimuli (i.e., light). The doxorubicin (DOX)-loaded H–LTDC was self-assembled from type-1-reactive oxygen species (ROStype1 )-mediated degradable chondroitin sulfate (CS) conjugated with a photosensitizer (PS), Pheophorbide-a, which has a spherical shape and a uniform size distribution. Under hypoxic conditions, ROSType1 was mainly generated due to the electron-rich sulfate groups in the polysaccharide backbone. The ROStype1 generated by H–LTDC allowed laser-triggered drug release at low oxygen concentrations. From the in vitro cytotoxicity tests with colon cancer cells (HCT-116), under laser irradiation, DOX-loaded H–LTDCs showed higher toxicity under hypoxic conditions than that under normoxic conditions. In vivo and ex vivo biodistribution studies demonstrated that H–LTDCs selectively accumulated in the tumor tissues. As a result, drug-loaded H–LTDCs exhibited high anti-tumor activity in vivo. Overall, we believe that this approach could represent a promising platform for the treatment of tumor and hypoxia-associated diseases without undesirable side effects.