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

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.
Key words: TMTP1; metastasis; near-infrared imaging; sentinel lymph node; micelles; cervical cancer