Theranostics 2019; 9(24):7325-7344. doi:10.7150/thno.35346

Research Paper

TMTP1-modified Indocyanine Green-loaded Polymeric Micelles for Targeted Imaging of Cervical Cancer and Metastasis Sentinel Lymph Node in vivo

Rui Wei1#, Guiying Jiang1#, MengQin Lv2, Songwei Tan3, Xueqian Wang1, Ying Zhou1, Teng Cheng4, Xueqin Gao3, Xi Chen1, Wei Wang1, Chenming Zou3, Fei Li1, Xiangyi Ma1, Junbo Hu2, Ding Ma1, Danfeng Luo1✉, Ling Xi1✉

1. Department of Obstetrics & Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, People's Republic of China
2. Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, People's Republic of China
3. Tongji School of Pharmacy, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, People's Republic of China
4. Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, People's Republic of China
# These authors have contributed equally to this work

Abstract

Metastasis is one of the most threatening aspects of cervical cancer. We developed a method to intraoperatively map the primary tumor, metastasis and metastatic sentinel lymph nodes (SLNs), providing real-time intraoperative guidance in cervical cancer.

Methods: TMTP1, a tumor metastasis targeting peptide, was employed to modify the indocyanine green (ICG)-loaded poly (ethylene glycol)- poly (lactic-co-glycolic acid) (PEG-PLGA) micelles. The cervical cancer subcutaneous tumor model and lung metastasis model were established to determine the active targeting of ICG-loaded TMTP1-PEG-PLGA micelles (ITM) for the primary tumor and occult metastasis of cervical cancer. Human cervical cancer HeLa cells engineered by firefly luciferase were injected into the right hocks of BALB/c nude mice to develop the SLN metastasis model. The ITM and control ICG-loaded PEG-PLGA micelles (IM) were injected into the right hind footpads in the SLN metastasis model, and the migration and retention of micelles were recorded under near-infrared fluorescence. K14-HPV16 transgenic mice were also used to detect the image capability of ITM to target cancerous lesions.

Results: ITM could actively target imaging of the primary tumor and cervical cancer metastasis. ITM quickly diffused from the injection site to SLNs along lymphatic capillaries and remained in the SLNs for 12 h. Moreover, ITM specifically accumulated in the tumor metastatic SLNs (T-SLNs), which could be successfully distinguished from normal SLNs (N-SLNs).

Conclusion: ITM could achieve active targeting of the primary tumor, metastasis and T-SLNs, providing precise and real-time intraoperative guidance for cervical cancer.

Keywords: TMTP1, metastasis, near-infrared imaging, sentinel lymph node, micelles, cervical cancer

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How to cite this article:
Wei R, Jiang G, Lv M, Tan S, Wang X, Zhou Y, Cheng T, Gao X, Chen X, Wang W, Zou C, Li F, Ma X, Hu J, Ma D, Luo D, Xi L. TMTP1-modified Indocyanine Green-loaded Polymeric Micelles for Targeted Imaging of Cervical Cancer and Metastasis Sentinel Lymph Node in vivo. Theranostics 2019; 9(24):7325-7344. doi:10.7150/thno.35346. Available from http://www.thno.org/v09p7325.htm