title: The breast cancer stem cell potency of copper(ii) complexes bearing nonsteroidal anti-inflammatory drugs and their encapsulation using polymeric nanoparticles.
abstract: We report the cancer stem cell (CSC) potency of a novel series of copper(ii)-phenanthroline complexes bearing nonsteriodial anti-inflammatory drugs: naproxen, tolfenamic acid, and indomethacin (2a-3c). Two of the complexes, 2a and 3c, kill breast CSC-enriched HMLER-shEcad cells (grown in both monolayer and three-dimensional cell cultures) to a significantly better extent than salinomycin, a well-established CSC toxin. The most potent complex in the series, 3c induces its cytotoxic effect by generating intracellular reactive oxygen species (ROS) and inhibiting cyclooxgenase-2 (COX-2) activity. Encapsulation of 3c using biodegradable methoxy poly(ethylene glycol)-b-poly(d,l-lactic-co-glycolic) acid (PEG-PLGA) copolymers at the appropriate feed (5%, 3c NP5) enhances breast CSC uptake and reduces overall toxicity. The nanoparticle formulation, 3c NP5selectively kills breast CSCs over bulk breast cancer cells, and evokes a similar cellular response to the payload, 3c. To the best of our knowledge, this is the first study to demonstrate that polymeric nanoparticles can be used to effectively deliver CSC-potent metal complexes into CSCs.
authors: Department of Chemistry, King's College London, London, SE1 1DB, UK. kogularamanan.suntharalingam@kcl.ac.uk.
authors: Arvin
authors: A
authors: Eskandari
authors: Janine N
authors: JN
authors: Boodram
authors: Paul B
authors: PB
authors: Cressey
authors: Chunxin
authors: C
authors: Lu
authors: Peter M
authors: PM
authors: Bruno
authors: Michael T
authors: MT
authors: Hemann
authors: Kogularamanan
authors: K
authors: Suntharalingam
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D004337:Drug Carriers; D011091:Polyesters; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D011092:Polyethylene Glycols; D003300:Copper