Tumor-targeted drug delivery with aptamers.

Cancer is one of the leading causes of death around the world. Tumor-targeted drug delivery is one of the major areas in cancer research. Aptamers exhibit many desirable properties for tumor-targeted drug delivery, such as ease of selection and synthesis, high binding affinity and specificity, low immunogenicity, and versatile synthetic accessibility. Over the last several years, aptamers have quickly become a new class of targeting ligands for drug delivery applications. In this review, we will discuss in detail about aptamer-based delivery of chemotherapy drugs (e.g. doxorubicin, docetaxel, daunorubicin, and cisplatin), toxins (e.g. gelonin and various photodynamic therapy agents), and a variety of small interfering RNAs. Although the results are promising which warrants enthusiasm for aptamer-based drug delivery, tumor homing of aptamer-based conjugates after systemic injection has only been achieved in one report. Much remains to be done before aptamer-based drug delivery can reach clinical trials and eventually the day-to-day management of cancer patients. Therefore, future directions and challenges in aptamer-based drug delivery are also discussed.

[1]  Andrew D Ellington,et al.  Aptamer:toxin conjugates that specifically target prostate tumor cells. , 2006, Cancer research.

[2]  J. Szostak,et al.  In vitro selection of RNA molecules that bind specific ligands , 1990, Nature.

[3]  Anton P. McCaffrey,et al.  Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors , 2009, Nature Biotechnology.

[4]  J. Peterse,et al.  Breast cancer metastasis: markers and models , 2005, Nature Reviews Cancer.

[5]  M. Salvatore,et al.  Nuclear imaging in cancer theranostics. , 2007, The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of....

[6]  M. Kris,et al.  Docetaxel (Taxotere) as a single agent and in combination chemotherapy for the treatment of patients with advanced non-small cell lung cancer. , 2000, Seminars in oncology.

[7]  Shuming Nie,et al.  Nanotechnology in cancer therapeutics: bioconjugated nanoparticles for drug delivery , 2006, Molecular Cancer Therapeutics.

[8]  Robert Langer,et al.  Nanotechnology and Aptamers: Applications in Drug Delivery , 2022 .

[9]  T. Wieman,et al.  Photodynamic therapy using mono-L-aspartyl chlorin e6 (Npe6) for the treatment of cutaneous disease: a Phase I clinical study. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[10]  G. Visani,et al.  Doxorubicin variants for hematological malignancies. , 2011, Nanomedicine.

[11]  Anna Moore,et al.  In vivo imaging of siRNA delivery and silencing in tumors , 2007, Nature Medicine.

[12]  A. Jemal,et al.  Cancer Statistics, 2010 , 2010, CA: a cancer journal for clinicians.

[13]  James O McNamara,et al.  Targeted inhibition of αvβ3 integrin with an RNA aptamer impairs endothelial cell growth and survival , 2005 .

[14]  Johannes Waltenberger,et al.  In vitro and in vivo studies of a VEGF121/rGelonin chimeric fusion toxin targeting the neovasculature of solid tumors , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[15]  P. Bouvet,et al.  AS-1411, a guanosine-rich oligonucleotide aptamer targeting nucleolin for the potential treatment of cancer, including acute myeloid leukemia. , 2010, Current opinion in molecular therapeutics.

[16]  Raymond J Winquist,et al.  Cancer stem cells as the relevant biomass for drug discovery. , 2010, Current opinion in pharmacology.

[17]  Y. Tabata,et al.  Simple PEG Modification of DNA Aptamer Based on Copper Ion Coordination for Tumor Targeting , 2011, Journal of biomaterials science. Polymer edition.

[18]  J. Gehl,et al.  Paclitaxel and doxorubicin in metastatic breast cancer. , 1996, Seminars in oncology.

[19]  C. Mello,et al.  Revealing the world of RNA interference , 2004, Nature.

[20]  Robert Langer,et al.  Quantum dot-aptamer conjugates for synchronous cancer imaging, therapy, and sensing of drug delivery based on bi-fluorescence resonance energy transfer. , 2007, Nano letters.

[21]  Weibo Cai,et al.  Nanoplatforms for targeted molecular imaging in living subjects. , 2007, Small.

[22]  Xiaohong Fang,et al.  Aptamers generated from cell-SELEX for molecular medicine: a chemical biology approach. , 2010, Accounts of chemical research.

[23]  A. Venturino,et al.  Doxorubicin (or epidoxorubicin) combined with ifosfamide in the treatment of adult advanced soft tissue sarcomas. , 1992, Annals of oncology : official journal of the European Society for Medical Oncology.

[24]  Robert Langer,et al.  Superparamagnetic Iron Oxide Nanoparticle-Aptamer Bioconjugates for Combined Prostate Cancer Imaging and Therapy , 2011 .

[25]  A. Fire,et al.  Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans , 1998, Nature.

[26]  Eunjung Kim,et al.  Prostate cancer cell death produced by the co-delivery of Bcl-xL shRNA and doxorubicin using an aptamer-conjugated polyplex. , 2010, Biomaterials.

[27]  S. Butcher,et al.  DNA mimicry by a high-affinity anti-NF-κB RNA aptamer , 2007, Nucleic acids research.

[28]  J. Behravan,et al.  Targeted delivery of daunorubicin to T-cell acute lymphoblastic leukemia by aptamer , 2010, Journal of drug targeting.

[29]  K. Berg,et al.  Photochemical internalisation increases the cytotoxic effect of the immunotoxin MOC31‐gelonin , 2000, International journal of cancer.

[30]  T. Fitzwater,et al.  Potent 2′-amino-, and 2′-fluoro-2′- deoxyribonucleotide RNA inhibitors of keratinocyte growth factor , 1997, Nature Biotechnology.

[31]  T. Tuschl,et al.  Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells , 2001, Nature.

[32]  Yi Lu,et al.  Molecular diagnostic and drug delivery agents based on aptamer-nanomaterial conjugates. , 2010, Advanced drug delivery reviews.

[33]  J. Cullen,et al.  The role of pathology in the identification of drug-induced hepatic toxicity , 2006, Expert opinion on drug metabolism & toxicology.

[34]  Robert Langer,et al.  Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA–PEG nanoparticles , 2008, Proceedings of the National Academy of Sciences.

[35]  T. Abribat,et al.  The rise and rise of drug delivery , 2005, Nature Reviews Drug Discovery.

[36]  U. Haberkorn,et al.  A new prostate carcinoma binding peptide (DUP-1) for tumor imaging and therapy. , 2005, Clinical cancer research : an official journal of the American Association for Cancer Research.

[37]  A. Jemal,et al.  Global Cancer Statistics , 2011 .

[38]  A. Puisieux,et al.  Metastasis: a question of life or death , 2006, Nature Reviews Cancer.

[39]  John O Trent,et al.  Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer. , 2009, Experimental and molecular pathology.

[40]  M. Giraud-Panis,et al.  Cisplatin is a DNA-damaging antitumour compound triggering multifactorial biochemical responses in cancer cells: importance of apoptotic pathways. , 2005, Current medicinal chemistry. Anti-cancer agents.

[41]  D. Jain,et al.  Cardiotoxicity of doxorubicin and other anthracycline derivatives , 2000, Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology.

[42]  Yin Zhang,et al.  In Vivo Imaging of RNA Interference , 2010, Journal of Nuclear Medicine.

[43]  Andrew D. Ellington,et al.  Aptamer mediated siRNA delivery , 2006, Nucleic acids research.

[44]  S. Prusiner,et al.  Thioaptamer interactions with prion proteins: sequence-specific and non-specific binding sites. , 2007, Journal of molecular biology.

[45]  Won Jong Kim,et al.  Dual-aptamer-based delivery vehicle of doxorubicin to both PSMA (+) and PSMA (-) prostate cancers. , 2011, Biomaterials.

[46]  J. Karp,et al.  Nanocarriers as an Emerging Platform for Cancer Therapy , 2022 .

[47]  L. Rajendran,et al.  Subcellular targeting strategies for drug design and delivery , 2010, Nature Reviews Drug Discovery.

[48]  Sanjiv S. Gambhir,et al.  Dual-Function Probe for PET and Near-Infrared Fluorescence Imaging of Tumor Vasculature , 2007, Journal of Nuclear Medicine.

[49]  S. Barth,et al.  Cell-specific induction of apoptosis by rationally designed bivalent aptamer-siRNA transcripts silencing eukaryotic elongation factor 2. , 2008, Current cancer drug targets.

[50]  Mark E. Davis,et al.  Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles , 2010, Nature.

[51]  S. Missailidis,et al.  Aptamers as inhibitors of target proteins , 2009, Expert opinion on therapeutic patents.

[52]  J. Gariépy,et al.  Phototoxic aptamers selectively enter and kill epithelial cancer cells , 2008, Nucleic acids research.

[53]  P. Lin,et al.  Angiopoietin/Tie2 signaling, tumor angiogenesis and inflammatory diseases. , 2005, Frontiers in bioscience : a journal and virtual library.

[54]  S D Jayasena,et al.  High-affinity and specific recognition of human thyroid stimulating hormone (hTSH) by in vitro-selected 2'-amino-modified RNA. , 1996, Nucleic acids research.

[55]  M. Ferrari.  Cancer nanotechnology: opportunities and challenges , 2005, Nature Reviews Cancer.

[56]  P. H. Moore,et al.  Effects of photodynamic therapy using mono-L-aspartyl chlorin e6 on vessel constriction, vessel leakage, and tumor response. , 1994, Cancer research.

[57]  Mark E. Davis,et al.  Nanoparticle therapeutics: an emerging treatment modality for cancer , 2008, Nature Reviews Drug Discovery.

[58]  Kai Chen,et al.  Multimodality molecular imaging of glioblastoma growth inhibition with vasculature-targeting fusion toxin VEGF121/rGel. , 2007, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[59]  Robert H. Silverman,et al.  Activation of the interferon system by short-interfering RNAs , 2003, Nature Cell Biology.

[60]  Weibo Cai,et al.  Semiconductor quantum dots for in vivo imaging. , 2007, Journal of nanoscience and nanotechnology.

[61]  Shu-Jyuan Yang,et al.  Aptamer-based tumor-targeted drug delivery for photodynamic therapy. , 2010, ACS nano.

[62]  Weibo Cai,et al.  Preparation of peptide-conjugated quantum dots for tumor vasculature-targeted imaging , 2008, Nature Protocols.

[63]  Anthony D. Keefe,et al.  Aptamers as therapeutics , 2010, Nature Reviews Drug Discovery.

[64]  Y. Jeong,et al.  A drug-loaded aptamer-gold nanoparticle bioconjugate for combined CT imaging and therapy of prostate cancer. , 2010, ACS nano.

[65]  Hao Hong,et al.  Molecular imaging and therapy of cancer with radiolabeled nanoparticles. , 2009, Nano today.

[66]  Robert Langer,et al.  Nanoparticle–aptamer bioconjugates for cancer targeting , 2006, Expert opinion on drug delivery.

[67]  D. Shangguan,et al.  Aptamers evolved from live cells as effective molecular probes for cancer study , 2006, Proceedings of the National Academy of Sciences.

[68]  P. Giangrande,et al.  Therapeutic applications of DNA and RNA aptamers. , 2009, Oligonucleotides.

[69]  S. K. Kim,et al.  Cellular resistance to the antimelanoma immunotoxin ZME-gelonin and strategies to target resistant cells , 1996, Cancer Immunology, Immunotherapy.

[70]  Jinming Gao,et al.  Theranostic nanomedicine for cancer. , 2008, Nanomedicine.

[71]  M. Blagosklonny,et al.  Analysis of FDA Approved Anticancer Drugs Reveals the Future of Cancer Therapy , 2004, Cell cycle.

[72]  B. Sullenger,et al.  RNA aptamers as reversible antagonists of coagulation factor IXa , 2002, Nature.

[73]  T. Yap,et al.  Targeting the HGF/c-Met Axis: State of Play , 2010, Molecular Cancer Therapeutics.

[74]  L. Gold,et al.  Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. , 1990, Science.

[75]  Weibo Cai,et al.  Multimodality Molecular Imaging of Tumor Angiogenesis , 2008, Journal of Nuclear Medicine.

[76]  S. Klußmann,et al.  Spiegelmers: Biostable Aptamers , 2003, Chembiochem : a European journal of chemical biology.

[77]  J. Richie,et al.  Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[78]  Weibo Cai,et al.  Imaging of integrins as biomarkers for tumor angiogenesis. , 2008, Current pharmaceutical design.

[79]  S. Klußmann,et al.  Toward third-generation aptamers: Spiegelmers and their therapeutic prospects. , 2003, Current opinion in drug discovery & development.

[80]  George M Whitesides,et al.  Nanoscience, nanotechnology, and chemistry. , 2005, Small.

[81]  D. Zelterman,et al.  Phase I Dose Escalation Trial of Weekly Docetaxel Plus Irinotecan in Patients with Advanced Cancer , 2002, Cancer biology & therapy.

[82]  Weibo Cai,et al.  Are quantum dots ready for in vivo imaging in human subjects? , 2007, Nanoscale research letters.

[83]  G. Mayer.  The chemical biology of aptamers. , 2009, Angewandte Chemie.

[84]  Sanjiv S Gambhir,et al.  Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in living subjects. , 2006, Nano letters.

[85]  Sanjiv S. Gambhir,et al.  How molecular imaging is speeding up antiangiogenic drug development , 2006, Molecular Cancer Therapeutics.

[86]  S. Klußmann,et al.  Polyetheylenimine-Polyplexes of Spiegelmer NOX-A50 Directed against Intracellular High Mobility Group Protein A1 (HMGA1) Reduce Tumor Growth in Vivo* , 2010, The Journal of Biological Chemistry.

[87]  F. Stirpe,et al.  Gelonin, a new inhibitor of protein synthesis, nontoxic to intact cells. Isolation, characterization, and preparation of cytotoxic complexes with concanavalin A. , 1980, The Journal of biological chemistry.

[88]  Yong Wang,et al.  Cell type–specific delivery of siRNAs with aptamer-siRNA chimeras , 2006, Nature Biotechnology.

[89]  D. S. Coffey,et al.  Identification and characterization of nuclease-stabilized RNA molecules that bind human prostate cancer cells via the prostate-specific membrane antigen. , 2002, Cancer research.

[90]  Xiaoling Zhang,et al.  Molecular Assembly of an Aptamer–Drug Conjugate for Targeted Drug Delivery to Tumor Cells , 2009, Chembiochem : a European journal of chemical biology.

[91]  J. Settleman,et al.  EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer , 2010, Oncogene.

[92]  M. Sioud.  On the delivery of small interfering RNAs into mammalian cells , 2005, Expert opinion on drug delivery.

[93]  David S Alberts,et al.  Maximizing the delivery of intraperitoneal therapy while minimizing drug toxicity and maintaining quality of life. , 2006, Seminars in oncology.

[94]  W. Cai,et al.  Multimodality imaging of vascular endothelial growth factor and vascular endothelial growth factor receptor expression. , 2007, Frontiers in bioscience : a journal and virtual library.

[95]  W. You,et al.  The hepatocyte growth factor/c-Met signaling pathway as a therapeutic target to inhibit angiogenesis. , 2008, BMB reports.

[96]  Robert Langer,et al.  An aptamer-doxorubicin physical conjugate as a novel targeted drug-delivery platform. , 2006, Angewandte Chemie.

[97]  W. Shim,et al.  Angiopoietin: A TIE(d) Balance in Tumor Angiogenesis , 2007, Molecular Cancer Research.

[98]  Mario Stevenson,et al.  Therapeutic potential of RNA interference. , 2004, The New England journal of medicine.

[99]  Hans Wolf,et al.  An aptamer-based quartz crystal protein biosensor. , 2002, Analytical chemistry.

[100]  Yin Zhang,et al.  Multimodality molecular imaging of CD105 (Endoglin) expression. , 2011, International journal of clinical and experimental medicine.