摘要
目的:对前期研究的适体修饰的多壁碳纳米管(MWCNTs)纳米靶向造影剂作进一步的研究探讨。方法:对纳米超声造影剂采用激光共聚焦显微镜及流式细胞仪进行体外细胞摄取评价。采用裸鼠移植瘤模型对造影剂进行体内靶向性评价、体内显影效果与代谢分布评价。结果:体外细胞学研究表明,该造影剂可被细胞摄取,且分布于细胞质中。体内靶向性评价结果表明,该造影剂具有肿瘤靶向性,且其在体内显影效果较好。结论:该新型造影剂能够靶向显影肿瘤部位,具有良好地临床应用的潜能。
Objective:To further study the nano-targeted contrast agent based on previous study.Methods:In vitro cell uptake evaluation of MWCNTs nano-ultrasound contrast agent was performed by laser confocal microscope and flow cytometry.The model of nude mouse transplantation was used to evaluate the targeting of contrast agent in vivo and to evaluate the development effect and metabolic distribution in vivo.Results:In vitro results showed that the contrast agent had good cell uptake.In vivo results showed that the contrast agent was tumor targeting and had good development effects.Conclusion:The new contrast agent can target tumor site and has potential of good clinical applications.
引文
[1]Siegel RL,Miller KD,Jemal A.Cancer statistics,2016[J].CA Cancer J Clin,2016,66(1):7-30.
[2]Adj B,Schwabe J,Rogasch J,et al.A direct comparison of contrast-enhanced ultrasound and dynamic contrast-enhanced magnetic resonance imaging for prostate cancer detection and prediction of aggressiveness[J]Eur Radiol,2018,28(5):1949-60.
[3]Hahn MA,Singh AK,Sharma P,et al.Nanoparticles as contrast agents for in-vivo bioimaging:current status and future perspectives[J].Anal Bioanal Chem,2011399(1):3-27.
[4]Kiessling F,Fokong S,Koczera P,et al.Ultrasound microbubbles for molecular diagnosis,therapy,and theranostics[J].J Nucl Med,2012,53(3):345-8.
[5]Ahmed HU,Bosaily ES,Brown LC,et al.Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer(PROMIS):a paired validating confirmatory study[J].Lancet,2017,389(10071):815-22.
[6]Ukimura O,Coleman JA,de la Taille A,et al.Contemporary role of systematic prostate biopsies:indications,techniques,and implications for patient care[J]Eur Urol,2013,63(2):214-30.
[7]Washington SL,Bonham M,Whitson JM,et al.Transrectal ultrasonography-guided biopsy does not reliably identify dominant cancer location in men with low-risk prostate cancer[J].BJU Int,2012,110(1):50-5.
[8]顾芬芬,胡楚玲,宫春爱,等.纳米靶向化学免疫疗法的研究进展[J].第二军医大学学报,2017,38(5):634-8.
[9]夏清明,顾芬芬,胡楚玲,等.纳米免疫制剂在抗肿瘤方面的应用[J].解放军药学学报,2017,33(6):557-60.
[10]顾芬芬,胡楚玲,台宗光,等.前列腺癌新型靶向纳米超声造影剂的合成及初步评价[J].药学与临床研究,2018,26(4):257-60.
[11]王增辉,陈斌龙,殷晴晴,等.pH超敏感纳米胶束的形状对其细胞摄取效率及肿瘤精确诊断的影响[J].药学学报,2018,53(5):797-805.
[12]Ying ZB,Li ML,Lei L,et al.Construction of folateconjugated epirubicin liposomes for enhacing the cellular uptake and the co-localization with nuclei of invasive breast cancer cells[J].J Chin Pharm Sci,2018,27(4):229-40.
[13]Carson AR,McTiernan CF,Lavery L,et al.Gene therapy of carcinoma using ultrasound-targeted microbubble destruction[J].Ultrasound Med Biol,2011,37(3):393-402.
[14]Kohler N,Sun C,Wang J,et al.Methotrexate-modified superparamagnetic nanoparticles and their intracellular uptake into human cancer cells[J].Langmuir,2005,21(19):8858-64.