Download Bionanotechnology used for capturing and restraining circulating

Bionanotechnology used for capturing and restraining circulating tumor
cells: eliminating the suffering and death from cancer metastasis
Haiyan Dong, Yusheng Lu, Jianguo Xu, Ning Zheng, Jian Liu, Lee Jia¶
Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of
Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.
¶ Corresponding
authors: [email protected]
Keywords: circulating tumor cells; cancer metastasis; cell surface biomarker; antibody/aptamer
nanomaterials; cancer metastasis chemoprevention
Abstract: During the four decades, the number of cancer survivors has increased from 3 million in 1971 to
nearly 14.5 million by 2014 in USA alone (1). This is worthy to celebrate, but this global expanding
population has highlighted the problem of cancer relapse and metastasis, which is the primary cause of
cancer suffering and mortality, and threatens the cancer survivors daily. Among those cancer survivors
30-70% will eventually face the metastatic nightmares within 2-5 years after surgery. The root cause of
cancer metastasis can be traced down to the presence of circulating tumor cells (CTCs) or circulating tumor
DNA (ctDNA, fragments mainly released from necrotic and apoptotic tumor cells) in the blood of cancer
survivors (2). CTCs in cancer survivors often show a low rate of proliferation when cancer survivors are in
remission and/or asymptomatic. Thus current anticancer chemotherapeutic, or target agents, and their related
nanomaterial conjugates that are originally designed to target highly proliferating cancer cells cannot be
used for killing CTCs in addition to their intolerable side effects. During the past ten years, CTCs have
received enormous attention as new theranostical biomarkers. However, little is known and done about
utilization of bionanotechnology for specifically capturing CTCs and restraining their activity in the
bloodstream of the asymptomatic cancer survivors in order to prevent the future cancer metastasis. We have
developed technology to separate and sort CTCs from patient blood, developed various cancer metastasis
chemopreventive agents with good safe and effective profiles to prevent CTCs from starting
activation-adhesion-invasion-extravasation metastasis cascade. Based on our cell surface biomarker analysis
that revealed that a single cell usually expresses various surface biomarkers at different abundance, we have
been developing safe bionanomaterials-conjugated with more than one (n>1) antibodies and aptamers that
can recognize, capture and restrain CTCs with enhanced specificity and efficacy, including aptamer
cyclization technology that enhances aptamer biostability via resistance to exonuclease digestion. In this
presentation, we will summarize the current status of CTCs research, and propose a conceptual framework
of using bionanotechnology for capturing and restraining circulating tumor cells to eliminate the suffering
and death from cancer metastasis.
References:
[1] DeSantis, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J. Clin. 2014; 64 252-271.
[2] Alix-Panabieres and Pantel. Challenges in circulating tumour cell research. Nat. Rev. Cancer. 2014; 14:623-31.
[3]
Xie, JJ., Lu, Y., Dong, HY., Zhao, RL., Chen, HN., Shen, WY., Sinko, PJ., Zhu, Y., Wang, JC., Shao, JW., Gao, Y., Xie, FW.,
Jia, L. Enhanced specificity in capturing and restraining circulating tumour cells with dual antibody-dendrimer conjugates. Adv.
Funct. Mater. 2015, 25, 1304–1313