title: Andrographolide-loaded polymerized phenylboronic acid nanoconstruct for stimuli-responsive chemotherapy.
abstract: Along with the successful discovery of paclitaxel as an anticancer drug, natural products have drawn great attention in drug discovery. Recently, andrographolide (AND) from Andrographis paniculata was reported to provide several benefits, including an anticancer effect. However, the extremely low solubility of the compound in an aqueous medium was an obstacle to overcome for the systemic administration and clinical application of AND. Based on our previous report, we formulated a water-soluble nanoconstruct by forming a boronic ester between the cis-1,3-diol of AND with hydrophilically polymerized phenylboronic acid (pPBA). The release of loaded AND was controlled by intracellular conditions, specifically, by low pH and high ATP concentrations, due to the pH- and diol-dependent affinity of the boronic ester. Because of the intrinsic property of the PBA moiety, the pPBA-AND nanoconstruct exhibited an excellent tumor targeting ability both in vitro and in vivo. Finally, a significant inhibition of tumor growth was observed in vivo. Taken together, our strategy, which is based on the formulation of a soluble nanoconstruct using hydrophilically polymerized PBA and a cis-diol, is plausible and provides a delivery system for a wide variety of chemotherapeutics. This strategy has applications not only in cancer therapy but also broader fields such as anti-inflammation or immunotherapy.
authors.affiliation: Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.
authors.forename: Jinhwan
authors.initials: J
authors.lastname: Kim
authors.affiliation: Center for Self-assembly and Complexity, Institute of Basic Science (IBS), Pohang 37673, Republic of Korea.
authors.forename: Junseok
authors.initials: J
authors.lastname: Lee
authors.affiliation: Center for Self-assembly and Complexity, Institute of Basic Science (IBS), Pohang 37673, Republic of Korea.
authors.forename: Yeong Mi
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.
authors.forename: Swapan
authors.initials: S
authors.lastname: Pramanick
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea.
authors.forename: Sooseok
authors.initials: S
authors.lastname: Im
authors.affiliation: Department of Chemistry, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea; Center for Self-assembly and Complexity, Institute of Basic Science (IBS), Pohang 37673, Republic of Korea; School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea. Electronic address: wjkim@postech.ac.kr.
authors.forename: Won Jong
authors.initials: WJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D001897:Boronic Acids / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005260:Female; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D058105:Polymerization; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D004224:Diterpenes; D011108:Polymers; C030419:andrographolide; C010686:benzeneboronic acid
keywords: Andrographolide; Boronic ester chemistry; Drug delivery; Phenylboronic acid; Tumor targeting