title: Role of integrated cancer nanomedicine in overcoming drug resistance.
abstract: Cancer remains a major killer of mankind. Failure of conventional chemotherapy has resulted in recurrence and development of virulent multi drug resistant (MDR) phenotypes adding to the complexity and diversity of this deadly disease. Apart from displaying classical physiological abnormalities and aberrant blood flow behavior, MDR cancers exhibit several distinctive features such as higher apoptotic threshold, aerobic glycolysis, regions of hypoxia, and elevated activity of drug-efflux transporters. MDR transporters play a pivotal role in protecting the cancer stem cells (CSCs) from chemotherapy. It is speculated that CSCs are instrumental in reviving tumors after the chemo and radiotherapy. In this regard, multifunctional nanoparticles that can integrate various key components such as drugs, genes, imaging agents and targeting ligands using unique delivery platforms would be more efficient in treating MDR cancers. This review presents some of the important principles involved in development of MDR and novel methods of treating cancers using multifunctional-targeted nanoparticles. Illustrative examples of nanoparticles engineered for drug/gene combination delivery and stimuli responsive nanoparticle systems for cancer therapy are also discussed.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, MA 02115, USA.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Iyer
authors.forename: Amit
authors.initials: A
authors.lastname: Singh
authors.forename: Srinivas
authors.initials: S
authors.lastname: Ganta
authors.forename: Mansoor M
authors.initials: MM
authors.lastname: Amiji
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D006801:Humans; D058990:Molecular Targeted Therapy; D050997:Nanomedicine / Q000379:methods* / Q000639:trends; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers
keywords: 1,2-distearoyl-sn-glycero 3-phosphocholine; AAc; AML; Acrylic acid; Acute myeloid leukemia; Arginine–glycine–aspartic acid; BCP; BK; Block copolymer; Bradykinin; CD; CSC; CTAB; Cancer stem cells; Cetyltrimethylammonium bromide; Chol; Cholesterol; Cyclodextrin; DDS; DLL4; DMAEMA; DOPG; DOX; DPPC; DSPC; Delta-like 4 ligand; Dex; Dexamethasone; Dioleoylphosphatidylglycerol; Dipalmitoylphosphatidylcholine; Doxorubicin; Drug delivery system; ECM; EGFR; EMT; EOEOVE; EPR; Enhanced permeability and retention; EpCAM; Epidermal growth factor receptor; Epithelial cell adhesion molecule; Epithelial–mesenchymal transition; Extracellular matrix; GILT; Gamma-interferon-inducible lysosomal thiol reductase; HDAC; HFMF; HIFU; HPMA; High intensity focused ultrasound; High-frequency magnetic field; Histone deacetylase; IARC; IPNs; Imaging; Infra-red; International agency for research on cancer; Interpenetrating networks; LCST; LTSL; Low thermosensitive liposomes; Lower critical solution temperature; MA; MAAc; MDR; MMPs; MPS; MRI; MSNP; MSNs; Magnetic resonance imaging; Maleic anhydride (MA); Matrix metalloproteinase; Mesoporous silica nanoparticles; Methacrylic acid; Mononuclear phagocytic system; Multi-drug resistance; Multifunctional nanosystems; N,N-dimethylaminoethyl methacrylate; NGF; NIR; NO; NSCLC; NTSL; Nerve growth factor; Nitric oxide; Non-small cell lung cancer; Non-thermosensitive liposomes; P-glycoprotein; P-gp; PAA; PAM; PCL; PDDA; PDEAAm; PDMAEMA; PEG; PEI; PEO; PGA; PGs; PHEA; PLGA; PNIPAAm; PSMA; PTMC; PVCL; PbAE; Poly(N,N-diethylacrylamide); Poly(N-(2-hydroxypropyl)methacrylamide); Poly(N-isopropyl acrylamide); Poly(N-vinlycaprolactam); Poly(amidoamine); Poly(caprolactone); Poly(d,l-lactide-co-glycolide); Poly(dimethyldiallylammonium chloride); Poly(ethylene glycol); Poly(ethylene oxide); Poly(glutamic acid); Poly(trimethylene carbonate); Poly(β-amino ester); Poly[2-(2-ethoxy)ethoxyethyl vinyl ether]; Poly[2-(dimethylamino)ethyl methacrylate]; Polyacrylamide; Polyethyleneimine; Prostaglandins; Prostate-specific membrane antigen; RGD; RNA interference; RNAi; SCLC; SP; SPIONs; Short hairpin RNA; Side population; Small cell lung cancer; Small interfering RNA; Superparamagnetic iron oxide nanoparticles; TF; TTSL; Targeted delivery; Tegafur; Thermosensitive liposomes; Tumor multidrug resistance; UCNPs; UCST; US; Ultrasound; Upconverting nanoparticles; Upper critical solution temperature; VEGF; VPF; Vascular endothelial growth factor; Vascular permeability factor; shRNA; siRNA; α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide