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Superior performance of aptamer in tumor penetration over antibody : implication of aptamer-based theranostics in solid tumors

Xiang, Dongxi, Zheng, Conglong, Zhou, Shu-Feng, Qiao, Shuxi, Tran, Phuong Ha-Lien, Pu, Chunwen, Li, Yong, Kong, Lingxue, Kouzani, Abbas Z., Lin, Jia, Liu, Ke, Li, Lianhong, Shigdar, Sarah and Duan, Wei 2015, Superior performance of aptamer in tumor penetration over antibody : implication of aptamer-based theranostics in solid tumors, Theranostics, vol. 5, no. 10, pp. 1083-1097, doi: 10.7150/thno.11711.

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Title Superior performance of aptamer in tumor penetration over antibody : implication of aptamer-based theranostics in solid tumors
Author(s) Xiang, Dongxi
Zheng, Conglong
Zhou, Shu-Feng
Qiao, Shuxi
Tran, Phuong Ha-LienORCID iD for Tran, Phuong Ha-Lien orcid.org/0000-0001-8463-7516
Pu, Chunwen
Li, Yong
Kong, LingxueORCID iD for Kong, Lingxue orcid.org/0000-0001-6219-3897
Kouzani, Abbas Z.ORCID iD for Kouzani, Abbas Z. orcid.org/0000-0002-6292-1214
Lin, Jia
Liu, Ke
Li, Lianhong
Shigdar, Sarah
Duan, WeiORCID iD for Duan, Wei orcid.org/0000-0001-5782-9184
Journal name Theranostics
Volume number 5
Issue number 10
Start page 1083
End page 1097
Total pages 15
Publisher Ivyspring International Publisher
Place of publication Sydney, N.S.W.
Publication date 2015
ISSN 1838-7640
Keyword(s) aptamer
targeted tumor therapeutics
tumor penetration
Summary Insufficient penetration of therapeutic agents into tumor tissues results in inadequate drug distribution and lower intracellular concentration of drugs, leading to the increase of drug resistance and resultant failure of cancer treatment. Targeted drug delivery to solid tumors followed by complete drug penetration and durable retention will significantly improve clinical outcomes of cancer therapy. Monoclonal antibodies have been commonly used in clinic for cancer treatment, but their limitation of penetrating into tumor tissues still remains because of their large size. Aptamers, as "chemical antibodies", are 15-20 times smaller than antibodies. To explore whether aptamers are superior to antibodies in terms of tumor penetration, we carried out the first comprehensive study to compare the performance of an EpCAM aptamer with an EpCAM antibody in theranostic applications. Penetration and retention were studied in in vitro three-dimensional tumorspheres, in vivo live animal imaging and mouse colorectal cancer xenograft model. We found that the EpCAM aptamer can not only effectively penetrate into the tumorsphere cores but can also be retained by tumor sphere cells for at least 24 h, while limited tumor penetration by EpCAM antibody was observed after 4 h incubation. As observed from in vivo live animal imaging, EpCAM aptamers displayed a maximum tumor uptake at around 10 min followed by a rapid clearance after 80 min, while the signal of peak uptake and disappearance of antibody appeared at 3 h and 6 h after intravenous injection, respectively. The signal of PEGylated EpCAM aptamers in xenograft tumors was sustained for 26 h, which was 4.3-fold longer than that of the EpCAM antibody. Consistently, there were 1.67-fold and 6.6-fold higher accumulation of PEGylated aptamer in xenograft tumors than that of antibody, at 3 h and 24 h after intravenous administration, respectively. In addition, the aptamer achieved at least a 4-time better tumor penetration in xenograft tumors than that of the antibody at a 200 μm distances from the blood vessels 3 h after intravenous injection. Taken together, these data indicate that aptmers are superior to antibodies in cancer theranostics due to their better tumor penetration, more homogeneous distribution and longer retention in tumor sites. Thus, aptamers are promising agents for targeted tumor therapeutics and molecular imaging.
Language eng
DOI 10.7150/thno.11711
Field of Research 111299 Oncology and Carcinogenesis not elsewhere classified
Socio Economic Objective 920102 Cancer and Related Disorders
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2015, Ivyspring International Publisher
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30075881

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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.