An aptamer-antibody complex (oligobody) as a novel delivery platform for targeted cancer therapies
| Autor: | Junho Chung, Ho Jin Sung, Beom Kyu Choi, Seok Chung, Kyun Heo, Eun Sook Lee, Sewoon Han, Hyun Jung Kim, Yun-Hee Kim, Sung Won Min, Han Gyul Kim, In Hoo Kim |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Vascular Endothelial Growth Factor A Lung Neoplasms Pegaptanib Aptamer Druggability Pharmaceutical Science Mice Nude Antineoplastic Agents Pharmacology 03 medical and health sciences 0302 clinical medicine Drug Delivery Systems Pharmacokinetics In vivo medicine Human Umbilical Vein Endothelial Cells Animals Humans Molecular Targeted Therapy Cotinine Mice Inbred BALB C biology business.industry Cancer Antibodies Monoclonal Hep G2 Cells Aptamers Nucleotide medicine.disease 030104 developmental biology A549 Cells 030220 oncology & carcinogenesis biology.protein Systemic administration Female Antibody business medicine.drug |
| Zdroj: | Journal of controlled release : official journal of the Controlled Release Society. 229 |
| ISSN: | 1873-4995 |
| Popis: | Aptamers have recently emerged as reliable and promising targeting agents in the field of biology. However, their therapeutic potential has yet to be completely assessed due to their poor pharmacokinetics for systemic administration. Here, we describe a novel aptamer-antibody complex, designated an "oligobody" (oligomer+antibody) that may overcome the therapeutic limitations of aptamers. To provide proof-of-principle study, we investigated the druggability of oligobody in vivo using cotinine conjugated t44-OMe aptamer, which is specific for the sequence of pegaptanib, and an anti-cotinine antibody. The antibody part of oligobody resulted in extended in vivo pharmacokinetics of the aptamer without influencing its binding affinity. Moreover, the aptamer of oligobody penetrated deeply into the tumor tissues whereas the anti-VEGF antibody did not. Finally, the systemic administration of this oligobody reduced the tumor burden in a xenograft mouse model. Together, these results suggested that our oligobody strategy may represent a novel platform for rapid, low-cost and high-throughput cancer therapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect