Aptamer/doxorubicin-conjugated nanoparticles target membranous CEMIP2 in colorectal cancer
Issued Date
2023-08-01
Resource Type
ISSN
01418130
eISSN
18790003
Scopus ID
2-s2.0-85163369731
Pubmed ID
37353120
Journal Title
International Journal of Biological Macromolecules
Volume
245
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Biological Macromolecules Vol.245 (2023)
Suggested Citation
Kianpour M., Huang C.W., Vejvisithsakul P.P., Wang J.Y., Li C.F., Shiao M.S., Pan C.T., Shiue Y.L. Aptamer/doxorubicin-conjugated nanoparticles target membranous CEMIP2 in colorectal cancer. International Journal of Biological Macromolecules Vol.245 (2023). doi:10.1016/j.ijbiomac.2023.125510 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/88009
Title
Aptamer/doxorubicin-conjugated nanoparticles target membranous CEMIP2 in colorectal cancer
Author's Affiliation
Other Contributor(s)
Abstract
The objectives were to identify the functional domains of a potential oncoprotein, cell migration inducing hyaluronidase 2 (CEMIP2), evaluate its expression levels and roles in colorectal cancer (CRC), and develop an aptamer-based nanoparticle for targeted therapy. Data mining on TCGA identified that CEMIP2 might play oncogenic roles in CRC. In a local cohort, CEMIP2 mRNA levels significantly stepwise increase in CRC patients with higher stages, and high CEMIP2 confers worse disease-free survival. In addition, CEMIP2 mRNA levels significantly correlated to hyaluronan levels in sera from CRC patients. Deletion mapping identified that CEMIP2 containing G8 and PANDER-like domains preserved hyaluronidase activity and oncogenic roles, including cell proliferation, anchorage-independent cell growth, cell migration and invasion, and human umbilical vein endothelial cell (HUVEC) tube formation in CRC-derived cells. A customized monoclonal mouse anti-human CEMIP2 antibody probing the PANDER-like domain (anti-289307) counteracted CEMIP2-mediated carcinogenesis in vitro. Cell-SELEX pinpointed an aptamer, aptCEMIP2(101), specifically interacted with the full-length CEMIP2, potentially involving its 3D structure. Treatments with aptCEMIP2(101) significantly reduced CEMIP2-mediated tumorigenesis in vitro. Mesoporous silica nanoparticles (MSN) carrying atpCEMIP2(101) and Dox were fabricated. Dox@MSN, MSN-aptCEMIP2(101), and Dox@MSN-aptCEMIP2(101) significantly suppressed tumorigenesis in vitro compared to the Mock, while Dox@MSN-aptCEMIP2(101) showed substantially higher effects compared to Dox@MSN and MSN-aptCEMIP2(101) in CRC-derived cells. Our study identified a novel oncogene and developed an effective aptamer-based targeted therapeutic strategy.