title: Design and cellular studies of a carbon nanotube-based delivery system for a hybrid platinum-acridine anticancer agent.
abstract: A three-component drug-delivery system has been developed consisting of multi-walled carbon nanotubes (MWCNTs) coated with a non-classical platinum chemotherapeutic agent ([PtCl(NH3)2(L)]Cl (P3A1; L=N-(2-(acridin-9-ylamino)ethyl)-N-methylproprionimidamide) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-5000] (DSPE-mPEG). The optimized P3A1-MWCNTs are colloidally stable in physiological solution and deliver more P3A1 into breast cancer cells than treatment with the free drug. Furthermore, P3A1-MWCNTs are cytotoxic to several cell models of breast cancer and induce S-phase cell cycle arrest and non-apoptotic cell death in breast cancer cells. By contrast, free P3A1 induces apoptosis and allows progression to G2/M phase. Photothermal activation of P3A1-MWCNTs to generate mild hyperthermia potentiates their cytotoxicity. These findings suggest that delivery of P3A1 to cancer cells using MWCNTs as a drug carrier may be beneficial for combination cancer chemotherapy and photothermal therapy.
authors: Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. Electronic address: cfahrenh@wakehealth.edu.
authors: Cale D
authors: CD
authors: Fahrenholtz
authors: Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA. Electronic address: dings0@wfu.edu.
authors: Song
authors: S
authors: Ding
authors: Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. Electronic address: bbernish@wakehealth.edu.
authors: Brian W
authors: BW
authors: Bernish
authors: Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA. Electronic address: mariah.l.wright@alumni.wfu.edu.
authors: Mariah L
authors: ML
authors: Wright
authors: Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA. Electronic address: zheny9@wfu.edu.
authors: Ye
authors: Y
authors: Zheng
authors: Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA. Electronic address: yangm11@wfu.edu.
authors: Mu
authors: M
authors: Yang
authors: Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA. Electronic address: yaox15@wfu.edu.
authors: Xiyuan
authors: X
authors: Yao
authors: Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA. Electronic address: donatigl@wfu.edu.
authors: George L
authors: GL
authors: Donati
authors: Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA. Electronic address: grossmd@wfu.edu.
authors: Michael D
authors: MD
authors: Gross
authors: Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA; Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC 27157, USA. Electronic address: bierbau@wfu.edu.
authors: Ulrich
authors: U
authors: Bierbach
authors: Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA; Comprehensive Cancer Center of Wake Forest University, Winston-Salem, NC 27157, USA. Electronic address: rasingh@wakehealth.edu.
authors: Ravi
authors: R
authors: Singh
mesh_terms: D000166:Acridines / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000628:therapy*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D037742:Nanotubes, Carbon / Q000737:chemistry*; D010789:Phototherapy / Q000379:methods*; D010984:Platinum / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; D037742:Nanotubes, Carbon; D010984:Platinum
keywords: Chemotherapy; Cytotoxicity; Drug delivery; Nanoparticle; Photothermal therapy; Triple negative breast cancer