磁性氧化铁纳米粒子应用于胰腺癌靶向诊疗的研究进展

摘要/Abstract

摘要：

胰腺癌预后极差，其早期诊断和治疗尤为关键。纳米技术已广泛应用于胰腺癌诊治，依靠纳米粒子的独特理化性质和其丰富的表面修饰手段可实现肿瘤部位的有效富集。磁性氧化铁纳米粒子（MIONPs）是胰腺癌诊治常用的纳米材料之一，具有良好的生物相容性。通过对其进行特殊的表面修饰，可应用于胰腺癌的靶向诊断和治疗。MIONPs可作为MRI的对比剂，通过修饰纳米粒子表面，可用于胰腺癌的靶向成像；还可将其改造为载药系统从而实现药物的靶向输送，提高治疗效果等。但是，MIONPs应用于胰腺癌诊疗仍然面临一些挑战，如纳米毒性和成本问题。随着技术发展，MIONPs有望在胰腺癌的个性化诊疗中发挥重要作用。

关键词:胰腺癌,磁性氧化铁纳米粒子,被动靶向,主动靶向

Abstract:

Pancreatic cancer has a very poor prognosis. Early diagnosis and treatment are especially critical for improving its prognosis. Nanotechnology has been widely used in the diagnosis and treatment of pancreatic cancer. Relying on the unique physicochemical properties of nanoparticles and their rich surface modifications, effective enrichment of tumor sites can be achieved. Magnetic iron oxide nanoparticles (MIONPs) is one of the commonly used nanomaterials in the diagnosis and treatment of pancreatic cancer, and has good biocompatibility. Through special surface modification, it can be used in targeted diagnosis and treatment of pancreatic cancer. MIONPs can be used as a contrast agent for MRI, and by modifying the surface, they also can be used in targeted imaging of pancreatic cancer. And they can also be modified as a drug delivery system to achieve targeted delivery of drugs and improve therapeutic effects. However, the application of MIONPs in pancreatic cancer diagnosis and treatment still faces some challenges, such as nanotoxicity and cost issues. With the development of technology, MIONPs are expected to play an important role in the personalized diagnosis and treatment of pancreatic cancer.

Key words:Pancreatic cancer,Magnetic iron oxide nanoparticle,Passive targeting,Active targeting

中图分类号:

R735.9

任加强, 武帅, 莫建涛, 周灿灿, 韩亮, 仵正. 磁性氧化铁纳米粒子应用于胰腺癌靶向诊疗的研究进展[J]. 外科理论与实践, 2024, 29(01): 61-66.

REN Jiaqiang, WU Shuai, MO Jiantao, ZHOU Cancan, HAN Liang, WU Zheng. Progress of magnetic iron oxide nanoparticles in targeted diagnosis and treatment of pancreatic cancer[J]. Journal of Surgery Concepts & Practice, 2024, 29(01): 61-66.

参考文献50

[1]	VINCENT A, HERMAN J, SCHULICK R, et al. Pancreatic cancer[J].Lancet,2011,378(9791):607-620. doi:10.1016/S0140-6736(10)62307-0pmid:21620466
[2]	MIZRAHI J D, SURANA R, VALLE J W, et al. Pancreatic cancer[J].Lancet,2020,395(10242):2008-2020. doi:S0140-6736(20)30974-0pmid:32593337
[3]	SIEGEL R L, MILLER K D, FUCHS H E, et al. Cancer statistics, 2022[J].CA Cancer J Clin,2022,72(1):7-33.
[4]	CHRISTENSON E S, JAFFEE E, AZAD N S. Current and emerging therapies for patients with advanced pancreatic ductal adenocarcinoma: a bright future[J].Lancet Oncol,2020,21:e135-e145.
[5]	GHARPURE K M, WU S Y, LI C, et al. Nanotechnology: future of oncotherapy[J].Clin Cancer Res,2015,21(14):3121-3130. doi:10.1158/1078-0432.CCR-14-1189pmid:26180057
[6]	RAJU G S R, DARIYA B, MUNGAMURI S K, et al. Nanomaterials multifunctional behavior for enlightened cancer therapeutics[J].Semin Cancer Biol,2021,69:178-189.
[7]	余日胜, 杨晓艳. 诊疗一体化超顺磁性氧化铁纳米颗粒用于胰腺癌靶向成像与治疗的研究进展[J].浙江医学,2022,44(16):1687-1693.
	YU R S, YANG X Y. Research progress of integrated diagnosis and treatment superparamagnetic iron oxide nanoparticles for targeted imaging and treatment of pancreatic cancer[J].Zhejiang Med J,2022,44(16):1687-1693.
[8]	ANCHORDOQUY T J, BARENHOLZ Y, BORASCHI D, et al. Mechanisms and barriers in cancer nanomedicine: addressing challenges, looking for solutions[J].ACS Nano,2017,11(1):12-18. doi:10.1021/acsnano.6b08244pmid:28068099
[9]	RAJITHA B, MALLA R R, VADDE R, et al. Horizons of nanotechnology applications in female specific cancers[J].Semin Cancer Biol,2021,69:376-390.
[10]	RAJU G S R, PAVITRA E, MERCHANT N, et al. Targe-ting autophagy in gastrointestinal malignancy by using nanomaterials as drug delivery systems[J].Cancer Lett,2018,419:222-232.
[11]	GU B, XU C, YANG C, et al. ZnO quantum dot labeled immunosensor for carbohydrate antigen 19-9[J].Biosens Bioelectron,2011,26(5):2720-2723. doi:10.1016/j.bios.2010.09.031pmid:20961745
[12]	WANG J P, YAU S T. Field-effect amperometric immuno-detection of protein biomarker[J].Biosens Bioelectron,2011,29:210-214.
[13]	KONG F Y, XU M T, XU J J, et al. A novel lable-free electrochemical immunosensor for carcinoembryonic antigen based on gold nanoparticles-thionine-reduced graphene oxide nanocomposite film modified glassy carbon electrode[J].Talanta,2011,85(5):2620-2625.
[14]	QIAN J, DAI H, PAN X, et al. Simultaneous detection of dual proteins using quantum dots coated silica nanoparticles as labels[J].Biosens Bioelectron,2011,28(1):314-319. doi:10.1016/j.bios.2011.07.045pmid:21820890
[15]	SWAIN S, SAHU P K, BEG S, et al. Nanoparticles for cancer targeting: current and future directions[J].Curr Drug Deliv,2016,13(8):1290-1302. pmid:27411485
[16]	SHETTY Y, PRABHU P, PRABHAKAR B. Emerging vistas in theranostic medicine[J].Int J Pharm,2019,558:29-42.
[17]	SEKHON B S, KAMBOJ S R. Inorganic nanomedicine-part 1[J].Nanomedicine,2010,6(4):516-522.
[18]	谭广, 李卉. 靶向性超顺磁性氧化铁纳米颗粒早期诊断胰腺癌的研究进展[J].医学综述,2020,26(9):1725-1729,1734.
	TAN G, LI H. Research progress of targeted superparamagnetic iron oxide nanoparticles in early diagnosis of pancreatic cancer[J].Med Recapitulate,2020,26(9):1725-1729,1734.
[19]	KALIAMURTHI S, DEMIR-KORKMAZ A, SELVARAJ G, et al. Viewing the emphasis on state-of-the-art magnetic nanoparticles: synthesis, physical properties, and applications in cancer theranostics[J].Curr Pharm Des,2019,25(13):1505-1523.
[20]	XU J K, ZHANG F F, SUN J J, et al. Bio and nanomaterials based on Fe3O4[J].Molecules,2014,19(12):21506-21528.
[21]	AIRES A, OCAMPO S M, CABRERA D, et al. BSA-coated magnetic nanoparticles for improved therapeutic properties[J].J Mater Chem B,2015,3(30):6239-6247. doi:10.1039/c5tb00833fpmid:32262742
[22]	FARRAN B, PAVITRA E, KASA P, et al. Folate-targeted immunotherapies: passive and active strategies for cancer[J].Cytokine Growth Factor Rev,2019,45:45-52.
[23]	LIN G, CHEN S, MI P. Nanoparticles targeting and remodeling tumor microenvironment for cancer theranostics[J].J Biomed Nanotechnol,2018,14(7):1189-1207. doi:10.1166/jbn.2018.2546pmid:29944095
[24]	ACCARDO A, ALOJ L, AURILIO M, et al. Receptor binding peptides for target-selective delivery of nanoparticles encapsulated drugs[J].Int J Nanomedicine,2014,9:1537-1557.
[25]	YANG F, JIN C, SUBEDI S, et al. Emerging inorganic nanomaterials for pancreatic cancer diagnosis and treatment[J].Cancer Treat Rev,2012,38(6):566-579. doi:10.1016/j.ctrv.2012.02.003pmid:22655679
[26]	张高瑞, 张玉婷, 赵雨萱, 等. MnFe2O4@CNS纳米探针在胰腺癌诊疗一体化中的价值[J].山东大学学报(医学版),2021,59(4):48-55.
	ZHANG G R, ZHANG Y T, ZHAO Y X, et al. MnFe2O4@CNS the value of nanoprobe in the integration of diagnosis and treatment of pancreatic cancer[J].J Shandong Univ(Med Edition),2021,59(4):48-55.
[27]	ZHANG G, LI N, QI Y, et al. Synergistic ferroptosis-gemcitabine chemotherapy of the gemcitabine loaded carbonaceous nanozymes to enhance the treatment and magnetic resonance imaging monitoring of pancreatic cancer[J].Acta Biomater,2022,142:284-297.
[28]	KHAN S, SETUA S, KUMARI S, et al. Superparamagnetic iron oxide nanoparticles of curcumin enhance gemcitabine therapeutic response in pancreatic cancer[J].Biomaterials,2019,208:83-97.
[29]	SIVAKUMAR B, ASWATHY R G, ROMERO-ABURTO R, et al. Highly versatile SPION encapsulated PLGA nanoparticles as photothermal ablators of cancer cells and as multimodal imaging agents[J].Biomater Sci,2017,5(3):432-443.
[30]	ROCHANI A K, BALASUBRAMANIAN S, RAVINDRAN GIRIJA A, et al. Dual mode of cancer cell destruction for pancreatic cancer therapy using Hsp90 inhibitor loaded polymeric nano magnetic formulation[J].Int J Pharm,2016,511(1):648-658.
[31]	DWIVEDI P, KIRAN S, HAN S, et al. Magnetic targeting and ultrasound activation of liposome-microbubble conjugate for enhanced delivery of anticancer therapies[J].ACS Appl Mater Interfaces,2020,12(21):23737-23751.
[32]	WANG S, ZHANG Q, LUO X F, et al. Magnetic graphene-based nanotheranostic agent for dual-modality mapping guided photothermal therapy in regional lymph nodal metastasis of pancreatic cancer[J].Biomaterials,2014,35(35):9473-9483. doi:10.1016/j.biomaterials.2014.07.064pmid:25175596
[33]	EL-ZAHABY S A, ELNAGGAR Y S R, ABDALLAH O Y. Reviewing two decades of nanomedicine implementations in targeted treatment and diagnosis of pancreatic cancer: an emphasis on state of art[J].J Control Release,2019,293:21-35.
[34]	PACHECO M, MAYORGA-MARTINEZ C C, VIKTOROVA J, et al. Microrobotic carrier with enzymatically encoded drug release in the presence of pancreatic cancer cellsviaprogrammed self-destruction[J].Applied Materials Today,2022,27:101494.
[35]	CHEN W, CHENG C A, ZINK J I. Spatial, temporal, and dose control of drug delivery using noninvasive magnetic stimulation[J].ACS Nano,2019,13(2):1292-1308. doi:10.1021/acsnano.8b06655pmid:30633500
[36]	ARACHCHIGE M P, LAHA S S, NAIK A R, et al. Functionalized nanoparticles enable tracking the rapid entry and release of doxorubicin in human pancreatic cancer cells[J].Micron,2017,92:25-31.
[37]	DONG Q, JIA X, WANG Y, et al. Sensitive and selective detection of Mucin1 in pancreatic cancer using hybridization chain reaction with the assistance of Fe3O4@polydopamine nanocomposites[J].J Nanobiotechnology,2022,20(1):94.
[38]	LOPEZ S, HALLALI N, LALATONNE Y, et al. Magneto-mechanical destruction of cancer-associated fibroblasts using ultra-small iron oxide nanoparticles and low frequency rotating magnetic fields[J].Nanoscale Adv,2021,4(2):421-436.
[39]	KOROLKOV I V, LUDZIK K, KOZLOVSKIY A L, et al. Carboranes immobilization on Fe₃O₄nanocomposites for targeted delivery[J].Mater today commun,2020,24:101247.
[40]	ZOU J, CHEN S, LI Y, et al. Nanoparticles modified by triple single chain antibodies for MRI examination and targeted therapy in pancreatic cancer[J].Nanoscale,2020,12(7):4473-4490. doi:10.1039/c9nr04976bpmid:32031201
[41]	WANG Z, TONG M, CHEN X, et al. Survivin-targeted nanoparticles for pancreatic tumor imaging in mouse model[J].Nanomedicine,2016,12(6):1651-1661. doi:10.1016/j.nano.2016.02.008pmid:26995092
[42]	SHEN J, LI Y, ZHU Y, et al. Multifunctional gadolinium-labeled silica-coated Fe₃O₄and CuInS2 nanoparticles as a platform forin vivotri-modality magnetic resonance and fluorescence imaging[J].J Mater Chem B,2015,3(14):2873-2882.
[43]	DOBIASCH S, SZANYI S, KJAEV A, et al. Synthesis and functionalization of protease-activated nanoparticles with tissue plasminogen activator peptides as targeting moiety and diagnostic tool for pancreatic cancer[J].J Nanobiotechnology,2016,14(1):81.
[44]	MENG H, NEL A E. Use of nano engineered approaches to overcome the stromal barrier in pancreatic cancer[J].Adv Drug Deliv Rev,2018,130:50-57.
[45]	ZHOU H, QIAN W, UCKUN F M, et al. IGF-1 receptor targeted nanoparticles for image-guided therapy of stroma-rich and drug resistant human cancer[J].Proc SPIE Int Soc Opt Eng,2016,9836:983610.
[46]	WANG M, LI Y, WANG M, et al. Synergistic interventional photothermal therapy and immunotherapy using an iron oxide nanoplatform for the treatment of pancreatic cancer[J].Acta Biomater,2022,138:453-462.
[47]	JAIDEV L R, CHELLAPPAN D R, BHAVSAR D V, et al. Multi-functional nanoparticles as theranostic agents for the treatment & imaging of pancreatic cancer[J].Acta Biomater,2017,49:422-433.
[48]	HUANG J, QIAN W, WANG L, et al. Functionalized milk-protein-coated magnetic nanoparticles for MRI-monitored targeted therapy of pancreatic cancer[J].Int J Nanomedicine,2016,11:3087-3099.
[49]	LEWINSKI N, COLVIN V, DREZEK R. Cytotoxicity of nanoparticles[J].Small,2008,4(1):26-49. doi:10.1002/smll.200700595pmid:18165959
[50]	FADEEL B, GARCIA-BENNETT A E. Better safe than sorry: understanding the toxicological properties of inorganic nanoparticles manufactured for biomedical applications[J].Adv Drug Deliv Rev,2010,62(3):362-374.