title: Combination of drug-conjugated SWCNT nanocarriers for efficient therapy of cancer stem cells in a breast cancer animal model.
abstract: Targeting breast cancer and more specifically cancer stem cell (CSC) subpopulation, responsible for tumor growth, resistance and self-renewal, using combination of therapeutic drugs selectively delivered via biocompatible nanocarriers, provides a novel approach for effective therapy. Here, we propose to evaluate the potential therapeutic efficacy of combining Paclitaxel and Salinomycin drugs actively targeted to both breast cancer and CSCs in xenograft murine model after conjugation with biocompatible CD44 antibody conjugated SWCNTs via hydrazone linker allowing pH-responsive release mechanism near the acidic tumor microenvironment. Both in vitro investigations on MDA-MB-231, sorted CSC negative or CSC positive fractions and in vivo evaluations on tumor-bearing mice using noninvasive bioluminescence and magnetic resonance imaging confirmed the enhanced therapeutic effect of the combined therapy compared to treatment with individual drug-conjugated nanocarriers or free drug suspensions. Thus, confirmed the great promise of the developed SWCNTs drug delivery system for effective breast cancer treatment by targeting and eradicating both whole tumor cells and CSCs populations.
authors.affiliation: King Saud University, College of Applied Medical Sciences, Department of Radiological Sciences, Riyadh, Saudi Arabia. Electronic address: aalfaraj@ksu.edu.sa.
authors.forename: Achraf
authors.initials: A
authors.lastname: Al Faraj
authors.affiliation: King Saud University, Prince Naif Health Research Center, Riyadh, Saudi Arabia.
authors.forename: Asma Sultana
authors.initials: AS
authors.lastname: Shaik
authors.affiliation: Jubail Industrial College, Department of Chemical and Process Engineering Technology, Jubail Industrial City, Saudi Arabia.
authors.forename: Elaref
authors.initials: E
authors.lastname: Ratemi
authors.affiliation: King Saud University, College of Medicine, Prince Naif Center for Immunology Research, Department of Pediatrics, Riyadh, Saudi Arabia.
authors.forename: Rabih
authors.initials: R
authors.lastname: Halwani
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000097:blood; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology; D006835:Hydrazones / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018396:Mucin-1 / Q000097:blood; D037742:Nanotubes, Carbon / Q000737:chemistry; D014411:Neoplastic Stem Cells / Q000187:drug effects; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D011714:Pyrans / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects; D000095662:Polyether Polyketides
chemical_list: D000906:Antibodies; D015295:Antigens, Tumor-Associated, Carbohydrate; D000970:Antineoplastic Agents; D004337:Drug Carriers; D018960:Hyaluronan Receptors; D006835:Hydrazones; D018396:Mucin-1; D037742:Nanotubes, Carbon; D017239:Paclitaxel; D011714:Pyrans; C090797:CA 27-29 antigen; C010327:salinomycin; D000095662:Polyether Polyketides
keywords: Breast cancer stem cells; Drug delivery system; Noninvasive imaging; Paclitaxel; Salinomycin; Single walled carbon nanotubes