title: A RNA-DNA Hybrid Aptamer for Nanoparticle-Based Prostate Tumor Targeted Drug Delivery.
abstract: The side effects of radio- and chemo-therapy pose long-term challenges on a cancer patient's health. It is, therefore, highly desirable to develop more effective therapies that can specifically target carcinoma cells without damaging normal and healthy cells. Tremendous efforts have been made in the past to develop targeted drug delivery systems for solid cancer treatment. In this study, a new aptamer, A10-3-J1, which recognizes the extracellular domain of the prostate specific membrane antigen (PSMA), was designed. A super paramagnetic iron oxide nanoparticle-aptamer-doxorubicin (SPIO-Apt-Dox) was fabricated and employed as a targeted drug delivery platform for cancer therapy. This DNA RNA hybridized aptamer antitumor agent was able to enhance the cytotoxicity of targeted cells while minimizing collateral damage to non-targeted cells. This SPIO-Apt-Dox nanoparticle has specificity to PSMA⁺ prostate cancer cells. Aptamer inhibited nonspecific uptake of membrane-permeable doxorubic to the non-target cells, leading to reduced untargeted cytotoxicity and endocytic uptake while enhancing targeted cytotoxicity and endocytic uptake. The experimental results indicate that the drug delivery platform can yield statistically significant effectiveness being more cytotoxic to the targeted cells as opposed to the non-targeted cells.
authors.affiliation: Department of Biomedical Engineering, College of Engineering, University of Arkansas, Fayetteville, AR 72701, USA. jcleach@uams.edu.
authors.forename: John C
authors.initials: JC
authors.lastname: Leach
authors.affiliation: Ocean Nanotech, 2143 Worth Lane, Springdale, AR 72764, USA. awang@oceannanotech.com.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, College of Engineering, University of Arkansas, Fayetteville, AR 72701, USA. kye@binghamton.edu.|Department of Biomedical Engineering, Thomas J. Watson School of Engineering and Applied Sciences, State University of New York in Binghamton, Binghamton, NY 13902, USA. kye@binghamton.edu.
authors.forename: Kaiming
authors.initials: K
authors.lastname: Ye
authors.affiliation: Department of Biomedical Engineering, College of Engineering, University of Arkansas, Fayetteville, AR 72701, USA. sjin@binghamton.edu.|Department of Biomedical Engineering, Thomas J. Watson School of Engineering and Applied Sciences, State University of New York in Binghamton, Binghamton, NY 13902, USA. sjin@binghamton.edu.
authors.forename: Sha
authors.initials: S
authors.lastname: Jin
mesh_terms: D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D052157:Aptamers, Nucleotide / Q000235:genetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000235:genetics; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods; D043425:Glutamate Carboxypeptidase II / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D012313:RNA / Q000235:genetics
chemical_list: D000954:Antigens, Surface; D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D058185:Magnetite Nanoparticles; D012313:RNA; D004317:Doxorubicin; D004247:DNA; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
keywords: aptamer; nanoparticle; prostate cancer; targeted drug delivery