title: Recent trends in cancer drug  resistance reversal strategies  using nanoparticles.
abstract: BACKGROUND
  Resistance to chemotherapy is a major obstacle in the successful amelioration of tumors in many cancer patients. Resistance is either intrinsic or acquired, involving mechanisms such as genetic aberrations, decreased influx and increased efflux of drugs. Strategies for the reversal of resistance involve the alteration of enzymes responsible for drug resistance, the modulation of proteins regulating apoptosis mechanisms and improving the uptake of drugs using nanotechnology. Novel strides in the reversal of drug resistance are emerging, involving the use of nanotechnology, targeting stem cells, etc.
  
  
  METHODS
  This paper reviews the most recent cancer drug reversal strategies involving nanotechnology for targeting cancer cells and cancer stem cells (CSCs), for enhanced uptake of micro- and macromolecular inhibitors.
  
  
  CONCLUSIONS
  Nanotechnology used in conjunction with existing therapies, such as gene therapy and P-glycoprotein inhibition, has been shown to improve the reversal of drug resistance; the mechanisms involved in this include specific targeting of drugs and nucleotide therapeutics, enhanced cellular uptake of drugs and improved bioavailability of drugs with poor physicochemical characteristics. Important strategies in the reversal of drug resistance include: a multifunctional nanoparticulate system housing a targeting moiety; therapeutics to kill resistant cancer cells and CSCs; cytotoxic drugs and a tumor microenvironment stimuli-responsive element, to release the encapsulated therapeutics.
authors.affiliation: Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX 78363, USA. Palakurthi@pharmacy.tamhsc.edu
authors.forename: Srinath
authors.initials: S
authors.lastname: Palakurthi
authors.forename: Venkata Kashyap
authors.initials: VK
authors.lastname: Yellepeddi
authors.forename: Kiran Kumar
authors.initials: KK
authors.lastname: Vangara
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D052157:Aptamers, Nucleotide / Q000008:administration & dosage; D004337:Drug Carriers / Q000008:administration & dosage*; D004351:Drug Resistance / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D035683:MicroRNAs / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D058990:Molecular Targeted Therapy / Q000295:instrumentation / Q000379:methods*; D053758:Nanoparticles / Q000008:administration & dosage*; D009369:Neoplasms / Q000188:drug therapy*; D014411:Neoplastic Stem Cells / Q000187:drug effects; D034741:RNA, Small Interfering / Q000008:administration & dosage; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D004337:Drug Carriers; D035683:MicroRNAs; D034741:RNA, Small Interfering