title: Nucleic Acid Bioconjugates in Cancer Detection and Therapy.
abstract: Nucleoside- and nucleotide-based chemotherapeutics have been used to treat cancer for more than 50 years. However, their inherent cytotoxicities and the emergent resistance of tumors against treatment has inspired a new wave of compounds in which the overall pharmacological profile of the bioactive nucleic acid component is improved by conjugation with delivery vectors, small-molecule drugs, and/or imaging modalities. In this manner, nucleic acid bioconjugates have the potential for targeting and effecting multiple biological processes in tumors, leading to synergistic antitumor effects. Consequently, tumor resistance and recurrence is mitigated, leading to more effective forms of cancer therapy. Bioorthogonal chemistry has led to the development of new nucleoside bioconjugates, which have served to improve treatment efficacy en route towards FDA approval. Similarly, oligonucleotide bioconjugates have shown encouraging preclinical and clinical results. The modified oligonucleotides and their pharmaceutically active formulations have addressed many weaknesses of oligonucleotide-based drugs. They have also paved the way for important advancements in cancer diagnosis and treatment. Cancer-targeting ligands such as small-molecules, peptides, and monoclonal antibody fragments have all been successfully applied in oligonucleotide bioconjugation and have shown promising anticancer effects in vitro and in vivo. Thus, the application of bioorthogonal chemistry will, in all likelihood, continue to supply a promising pipeline of nucleic acid bioconjugates for applications in cancer detection and therapy.
authors.affiliation: Sun Pharmaceutical Industries Inc., Analytical Research and Development, 270 Prospect Plains Road, Cranbury, NJ, 08512, USA.
authors.forename: Pradeepkumar L
authors.initials: PL
authors.lastname: Patel
authors.affiliation: Department of Chemistry and Biochemistry, Seton Hall University, 400 South Orange Avenue, South Orange, NJ, 07079, USA.
authors.forename: Niki K
authors.initials: NK
authors.lastname: Rana
authors.affiliation: Department of Chemistry and Biochemistry, Seton Hall University, 400 South Orange Avenue, South Orange, NJ, 07079, USA.
authors.forename: Mayurbhai R
authors.initials: MR
authors.lastname: Patel
authors.affiliation: Department of Chemistry and Biochemistry, Seton Hall University, 400 South Orange Avenue, South Orange, NJ, 07079, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Kozuch
authors.affiliation: Department of Chemistry and Biochemistry, Seton Hall University, 400 South Orange Avenue, South Orange, NJ, 07079, USA. david.sabatino@shu.edu.
authors.forename: David
authors.identifier: http://orcid.org/0000-0002-9797-0833
authors.initials: D
authors.lastname: Sabatino
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D009696:Nucleic Acids / Q000737:chemistry* / Q000627:therapeutic use; D009841:Oligonucleotides / Q000737:chemistry / Q000627:therapeutic use; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use; D054852:Small Molecule Libraries / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D009696:Nucleic Acids; D009841:Oligonucleotides; D010455:Peptides; D054852:Small Molecule Libraries
keywords: anticancer agents; bioconjugation; bioorthogonal chemistry; nucleic acids