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.

Multiplexed NIR‐II Probes for Lymph Node‐Invaded Cancer Detection and Imaging‐Guided Surgery

“…The recent introduction of near‐infrared tracers, such as ICG, permits real‐time transcutaneous and intraoperative visualization of lymphatic vessels and sentinel LNs. Currently, a huge number of clinical trials have showed that ICG method can be used as a reliable and safe alternative to the radiotracer method, which reduces operating time and potentially improve localization of the sentinel LNs . However, the ICG based clinically used contrast agents suffer from severe photobleaching, poor imaging detection depth, signal contrast, and sensitivity.…”

Systemic Review of Biodegradable Nanomaterials in Nanomedicine

“…In vivo experiments demonstrated that these nanoparticles accumulate in lymph nodes, suggesting that they can be used as a means to detect metastasized cancer [69]. Similarly, MTP1, a tumor metastasis targeting peptide, has been employed to modify the indocyanine green (ICG)-loaded PEG-PLGA micelles for targeted imaging of cervical cancer and metastasis [72].…”

Acetylation stabilizes chloride intracellular channel 1 that exerts a tumor-promoting role by activation of nuclear factor kappa B in cervical cancer

“…Cell proliferation ability was evaluated by Cell Counting Kit (CCK)-8 assay. Briefly, cells at a density of 4×10 3 were seeded in 96-well plates in quintuplicate. After treatment, the plates were incubated for 0, 24, 48, 72, 96, or 120 h at 37°C.…”

“…The mortality of cervical cancer in low-income and middle-income countries is 18 times higher than that in developed countries [2]. Although the improvement in therapeutic strategies in the past few decades, the prognosis of patients with advanced or recurrent metastatic cervical cancer remains poor [3].…”