title: Biodegradable nanocomplex from hyaluronic acid and arginine based poly(ester amide)s as the delivery vehicles for improved photodynamic therapy of multidrug resistant tumor cells: An in vitro study of the performance of chlorin e6 photosensitizer.
abstract: Photodynamic therapy (PDT), which enables the localized therapeutic effect by light irradiation, provides an alternative and complementary modality for the treatment of tumor. However, the aggregation of photosensitizers in acidic microenvironment of tumor and the non-targeted distribution of photosensitizers in normal tissues significantly affect the PDT efficiency. In this study, we developed a biodegradable nanocomplex HA-Arg-PEA from hyaluronic acid (HA) and arginine based poly(ester amide)s (Arg-PEA) as the nanocarrier for chlorin e6 (Ce6). HA enhanced the tumor-specific endocytosis mediated by the overexpression of CD44 receptor. Arg-PEA not only provide electrostatic interaction with HA to form self-assembled nanostructure, but also improve the monomerization of Ce6 at physiological pH as well as mildly acidic pH. The biodegradable characteristic of HA-Arg-PEA nanocomplex enabled the intracellular delivery of Ce6, in which its release and generation of singlet oxygen can be accelerated by enzymatic degradation of the carrier. The in vitro PDT efficiency of Ce6-loaded HA-Arg-PEA nanocomplex was examined in CD44 positive MDA-MB-435/MDR multidrug resistant melanoma cells. CD44-mediated uptake of Ce6-loaded HA-Arg-PEA nanocomplex significantly improved Ce6 level in MDA-MB-435/MDR cells within short incubation time, and the PDT efficiency in inhibiting multidrug resistant tumor cells was also enhanced at higher Ce6 concentrations. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1487-1499, 2017.
authors.affiliation: Department of Fiber Science and Apparel Design, Cornell University, Ithaca, New York, 14853-4401.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ji
authors.affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
authors.forename: Jihui
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Fiber Science and Apparel Design, Cornell University, Ithaca, New York, 14853-4401.|Biomedical Engineering Field. Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York, 14853-4401.
authors.forename: Chih-Chang
authors.initials: CC
authors.lastname: Chu
mesh_terms: D001120:Arginine / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D063566:Biodegradable Plastics / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002735:Chlorophyllides; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011091:Polyesters / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011166:Porphyrins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D063566:Biodegradable Plastics; D002735:Chlorophyllides; D004337:Drug Carriers; D017319:Photosensitizing Agents; D011091:Polyesters; D011166:Porphyrins; C062985:phytochlorin; D006820:Hyaluronic Acid; D001120:Arginine
keywords: biodegradable nanocarrier; chlorin e6; hyaluronic acid; photodynamic therapy; poly (ester amide)s