In Vivo Optical Imaging And The Research On Targeting Therapy Based On Potential Biomarker Of Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC), a malignant tumor of the nasopharynx with astrong geographical distribution, has a high incidence in Guangdong, China,consequently named “Guangdong tumor”. Since the occurrence site is relatively smalland hidden, adjacent with many important organs, the symptom is changing or notobvious, resulting in misdiagnosis, late diagnosis with a poor effect and very lowfive-year survival rate, which severely affect human health. Thus, it is in urgent need todiscover new biomarkers of NPC for targeted diagnosis and treatment. The bionicnano-carrier with good biocompatibility and targeting is one of the effective means to killtumor specifically and avoid the other normal tissues from drug toxicity. To achievebetter research on NPC, there is a serious need for establishing visible animal models forNPC that enable dynamic monitoring of the formation, development and metastasis ofNPC, so as to effectively assess the effect of diagnosis and treatment for NPC.This article aims to look for potential biomarkers of NPC, establish visibleanimal models for NPC with a high signal-to-noise ratio, and use high-density lipoproteinbionic nano-carrier for effective targeted diagnosis and treatment of NPC. The results arelisted below:(1) We discovered that scavenger receptor class B member1(SR-B1) had a highexpression in NPC cells and pathological tissues of NPC patients. So SR-B1was definedto be a potential biomarker of NPC. Result indicated that NPC cells with high expressionof SR-B1have stronger ability of lateral migration and weaker ability of vertical invasion.In addition, the expression of SR-B1does not affect the cell growth and NPCtumorigenicity. (2) We discovered that HDL-mimicking peptide-phospholipid scaffold (HPPS) canspecifically target NPC tumors with high SR-B1expression, and successfully inhibit theformation and development of NPC in vivo by inhibiting the lateral migration of thetumor and colony formation.(3) We tried to use HPPS carrying chol-si-bmi1for the targeted therapy of NPC. Atthe cell level, it effectively inhibited lateral migration and colony formation rate of NPC.However, at the animal level, there was no significant inhibitory effect.(4) We established a series of visible animal models for NPC labeled by fluorescentproteins, providing good animal models for in vivo optical imaging and targetedtreatment of NPC. We obtained NPC cell line5-8F labeled with super bright far-redfluorescent protein (mLumin), which has good subcutaneous tumorigenicity andmetastasis. We also obtained NPC cell line5-8F-sh-SR-B1labeled with far-redfluorescent protein (Katushka S158A), which has no tumorigenicity. Results proved thattumorigenicity activity of these cell lines is closely related to the rate of side populationcells.(5) We established a visible animal model for NPC based on the three fusionreporter gene that included herpes simplex virus type1thymidine kinase, mLumin andfirefly luciferase. This model can be used for fluorescent imaging, bioluminescentimaging and microPET imaging simultaneously. Because of the introduction of far-redprotein into the triple fusion reporter gene, the detecting ability of in vivo fluorescentimaging was enhanced, which provides a multi-labeled animal model for the research onmulti-mode imaging of tumors.In this work, we discovered a potential biomarker for NPC (SR-B1), a membraneprotein that can act as a good transport target for diagnosis and treatment of NPC. HPPSwas proved to delay the growth of NPC effectively and enable cytosolic release of carriedsiRNA in NPC cells for gene therapy. Moreover, a series of visible animal models for NPC was established, making it convenient for dynamic monitoring of NPC occurrence,development and metastasis as well as effective assessment of efficacy and intuitivejudgment of treatment means.