| Purpose: Metastasis is one of the most threatening aspects in cervical cancer.The precise stage of cervical cancer and the timely targeted diagnosis and treatment of metastases can fundamentally improve the prognosis of cervical cancer.The introduction of near-infrared fluorescence imaging technology as a new treatment method has increasingly attracted the attention of scientists.Herein,we developed a method to intraoperatively map primary tumor,metastasis and metastases sentinel lymph node(SLN),in order to provide more accurate and real-time intraoperative guidance in cervical cancer and realize the treatment of cervical cancer under the guidance of imaging.Methods: 1.TMTP1 is employed to modify the ICG-loaded PEG-PLGA micelles.The micelles were prepared by nanoparticle-precipitation method.And the control was ICG-loaded micelles without peptide TMTP1-modified surface.2.The cervical cancer subcutaneous tumor model and the lung metastasis model were established to determine the active targeting of TMTP1-ICG-NP micelles for primary tumor and metastasis of cervical cancer.3.Free ICG and ICG-loaded micelles modified with/without TMTP1 were compared in normal mice to optimize SLN retention time and signal to background ratio.4.SLN metastasis model was developed by right hock injection of firefly luciferase engineered human cervical caner Hela cells.TMTP1-ICG-NP and ICG-NP micelles were intradermally injected into the right hind footpads and longitudinal fluorescence optical imaging was carried out to record the migration and retention of the imaging tracers.5.To compare ICG-loaded micelles imaging of tumor metastasis SLN(T-SLN)and normal SLN(N-SLN),the same ICG-loaded micelles were intradermally injected into the bilateral hind footpads of the right hela tumor PO LN metastasis model.6.K14-HPV16 transgenics mice were used to detect the image capability of TMTP1-ICG-NP micelles to target precancerous lesions.7.After injection of TMTP1-ICG-NP,laser irradiation was performed on the tumor site to examine the photothermal(PTT)and photodynamic(PDT)effect of the TMTP1-ICG-NP micelles in a subcutaneous tumor model of cervical cancer.Results: 1.We successfully prepared TMTP1-ICG-NP micelles,which is characterized that the polymer PEG-PLGA is used as a carrier to form micelle particles,the ICG is loaded internal and TMTP1 peptide is modified at the surface of the micelles.2.TMTP1-ICG-NP was able to produce a strong optical signal for primary tumor and metastasis of cervical cancer.3.TMTP1-ICG-NP could quickly diffuse from injection site to SLN along lymphatic capillaries and remain in the SLN for 24 h.4.TMTP1-ICG-NP could specifically accumulate in the tumor metastasis SLN.5.The TMTP1-ICG-NP could distinguish the tumor metastasis SLN and the normal SLN.6.TMTP1-ICG-NP could actively accumulate in precancerous lesions of the cervical epithelium,especially in the epithelium protruding to the interstitial site.7.The PTT/PDT effect of TMTP1-ICG-NP in vivo could effectively inhibit the growth of subcutaneous tumors of cervical cancer.Conclusions: TMTP1-ICG-NP could achieve active targeting of primary tumor,metastasis and metastases SLN,thus providing accurate and real-time intra-operative guidance in the surgery and timely diagnosis of metastases and sentinel lymph nodes.The highly effective accumulation of TMTP1-ICG-NP into the solid tumors gives these nanoparticles great improvement in the tumor PTT/PDT therapy efficacy.The multifunctional properties of TMTP1-ICG-NP provide a promising strategy to realize molecular imaging-guided tumor phototherapy of cervical cancer. |
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