基于纳米技术的膀胱癌治疗方法研究进展

doi:10.3969/j.issn.1674-8115.2023.12.012

上海交通大学学报（医学版） ›› 2023, Vol. 43 ›› Issue (12): 1562-1568.doi: 10.3969/j.issn.1674-8115.2023.12.012

基于纳米技术的膀胱癌治疗方法研究进展

杨晨凯¹(), 李威², 曹向乾¹, 何磊²^,³, 李圣洲¹, 沈兵¹()

^1.上海交通大学医学院附属第一人民医院泌尿外科，上海 200080
^2.海军军医大学纳米医学研究室，上海细胞工程重点实验室，上海 200433
^3.上海理工大学健康科学与工程学院，上海 200093

收稿日期:2023-08-10 接受日期:2023-11-20 出版日期:2023-12-28 发布日期:2024-02-01
通讯作者: 沈兵，电子信箱：urodrshenbing@shsmu.edu.cn。
作者简介:杨晨凯（1998—），男，硕士生；电子信箱：derekkaikai@163.com。
基金资助:
国家自然科学基金(82072821);上海市松江区自然科学基金(20SJKJGG250)

Research progress in the treatment of bladder cancer based on nanotechnology

YANG Chenkai¹(), LI Wei², CAO Xiangqian¹, HE Lei²^,³, LI Shengzhou¹, SHEN Bing¹()

^1.Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
^2.Department of Nanomedicine, Naval Medical University, Shanghai Key Laboratory of Cell Engineering, Shanghai 200433, China
^3.School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China

Received:2023-08-10 Accepted:2023-11-20 Online:2023-12-28 Published:2024-02-01
Contact: SHEN Bing, E-mail: urodrshenbing@shsmu.edu.cn.
Supported by:
National Natural Science Foundation of China(82072821);Shanghai Songjiang Municipal Natural Science Foundation(20SJKJGG250)

摘要/Abstract

摘要：

膀胱癌是泌尿系统最常见的恶性肿瘤。目前，膀胱癌的临床治疗方案主要包括手术、化学治疗（化疗）、放射治疗（放疗）、免疫治疗、靶向治疗、光动力治疗和联合治疗等。膀胱癌的传统治疗和给药方案主要取决于肿瘤的分期和转移程度。然而，在非手术治疗过程中药物缺乏特异性和靶向性，一旦剂量控制不当，药物攻击癌细胞时对正常细胞造成损伤等会导致疗效差、不良反应多等问题。纳米医学是一门新兴的交叉学科，利用纳米材料和技术的纳米医药具有靶向递送和高效低毒等优点，为传统治疗提供了颠覆性的技术。许多纳米技术已经成为医学领域临床研究的热点。纳米颗粒可以通过改变其表面性质和功能化修饰来实现主动或被动靶向，将药物精准递送到靶器官内的靶细胞（例如膀胱癌细胞），从而提高药物的局部浓度，减少对正常细胞的损伤，进而提高治疗效果。该文综述了膀胱癌经典治疗和新型治疗方案进展，并重点介绍了纳米技术在膀胱癌治疗中的潜在应用及未来发展方向，为膀胱癌的个性化治疗和临床转化提供参考。

关键词: 膀胱癌, 纳米技术, 靶向效应, 治疗

Abstract:

Bladder cancer is the most common malignant tumor in the urinary system. Currently, the clinical treatment options for bladder cancer mainly include surgery, chemotherapy, radiotherapy, immunotherapy, targeted therapy, photodynamic therapy, combination therapy, etc. The conventional treatment and administration strategies for bladder cancer primarily depend on the tumor stage and the extent of metastasis. However, in the process of non-surgical treatment, drugs lack specificity and targeting. Once the dosage is improperly controlled, drugs will damage normal cells when attacking cancer cells, which will lead to poor efficacy and multiple side effects. Nanomedicine is an emerging interdisciplinary field that utilizes nanomaterials and technologies in nanomedicine to provide disruptive technologies for traditional treatments, with advantages such as targeted delivery and high efficiency with low toxicity. Many nanotechnologies have become hot topics in clinical research in the field of medicine. Functionalized nanoparticles can actively or passively target specific cells within target organs, such as bladder cancer cells, by altering their surface properties, thereby enhancing drug delivery precision, reducing damage to normal cells, and improving treatment efficacy. This article provides an overview of the progress in classical and novel treatment approaches to bladder cancer, with a particular focus on the potential applications and future development directions of nanotechnology in the treatment of bladder cancer, providing important reference for personalized therapy and clinical translation in bladder cancer.

Key words: bladder cancer, nanotechnology, targeting effect, treatment

中图分类号:

R737.14

杨晨凯, 李威, 曹向乾, 何磊, 李圣洲, 沈兵. 基于纳米技术的膀胱癌治疗方法研究进展[J]. 上海交通大学学报（医学版）, 2023, 43(12): 1562-1568.

YANG Chenkai, LI Wei, CAO Xiangqian, HE Lei, LI Shengzhou, SHEN Bing. Research progress in the treatment of bladder cancer based on nanotechnology[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(12): 1562-1568.

参考文献 65

1	SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249.
2	TEOH J Y, HUANG J, KO W Y, et al. Global trends of bladder cancer incidence and mortality, and their associations with tobacco use and gross domestic product per capita[J]. Eur Urol, 2020, 78(6): 893-906.
3	SIEGEL R L, MILLER K D, WAGLE N S, et al. Cancer statistics, 2023[J]. CA Cancer J Clin, 2023, 73(1): 17-48.
4	CHEN W. Cancer statistics: updated cancer burden in China[J]. Chin J Cancer Res, 2015, 27(1): 1.
5	AMIN H A A, KOBAISI M H, SAMIR R M. Schistosomiasis and bladder cancer in Egypt: truths and myths[J]. Open Access Maced J Med Sci, 2019, 7(23): 4023-4029.
6	MOCH H, CUBILLA A L, HUMPHREY P A, et al. The 2016 WHO classification of tumours of the urinary system and male genital organs-part A: renal, penile, and testicular tumours[J]. Eur Urol, 2016, 70(1): 93-105.
7	BOUCHELOUCHE K. Diagnostic applications of nuclear medicine: kidney and bladder cancer[M/OL]//STRAUSS H W, MARIANI G, VOLTERRANI D, et al. Nuclear Oncology. Cham: Springer International Publishing, 2017: 839-881[2023-08-09]. https://doi.org/10.1007/978-3-319-26236-9_20.
8	BARTON M K. High morbidity and mortality found for high-risk, non-muscle-invasive bladder cancer[J]. CA Cancer J Clin, 2013, 63(6): 371-372.
9	BABJUK M, BÖHLE A, BURGER M, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016[J]. Eur Urol, 2017, 71(3): 447-461.
10	LIU B, GAO X, HAN B, et al. Mouse model to explore the therapeutic effect of nano-doxorubicin drug delivery system on bladder cancer[J]. J Nanosci Nanotechnol, 2021, 21(2): 914-920.
11	DOHERTY A P, TRENDELL-SMITH N, STIRLING R, et al. Perivesical fat necrosis after adjuvant intravesical chemotherapy[J]. BJU Int, 1999, 83(4): 420-423.
12	MESSING E M, TANGEN C M, LERNER S P, et al. Effect of intravesical instillation of gemcitabine vs saline immediately following resection of suspected low-grade non-muscle-invasive bladder cancer on tumor recurrence: SWOG S0337 randomized clinical trial[J]. JAMA, 2018, 319(18): 1880-1888.
13	LAMM D L, BLUMENSTEIN B A, CRISSMAN J D, et al. Maintenance bacillus Calmette-Guerin immunotherapy for recurrent Ta, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study[J]. J Urol, 2000, 163(4): 1124-1129.
14	PETTENATI C, INGERSOLL M A. Mechanisms of BCG immunotherapy and its outlook for bladder cancer[J]. Nat Rev Urol, 2018, 15(10): 615-625.
15	LENIS A T, LEC P M, CHAMIE K, et al. Bladder cancer: a review[J]. JAMA, 2020, 324(19): 1980-1991.
16	WITJES J A, BABJUK M, BELLMUNT J, et al. EAU-ESMO consensus statements on the management of advanced and variant bladder cancer: an international collaborative multistakeholder effort: under the auspices of the EAU-ESMO guidelines committees[J]. Eur Urol, 2020, 77(2): 223-250.
17	ALFRED W J, MAX B H, CARRIÓN A, et al. European association of urology guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2023 guidelines[J]. Eur Urol, 2024, 85(1): 17-31.
18	PLOUSSARD G, DANESHMAND S, EFSTATHIOU J A, et al. Critical analysis of bladder sparing with trimodal therapy in muscle-invasive bladder cancer: a systematic review[J]. Eur Urol, 2014, 66(1): 120-137.
19	CANIL C. Bladder cancer[M/OL]//ENNA S J, BYLUND D B. xPharm: the comprehensive pharmacology reference. Amsterdam: Elsevier, 2007: 1-4[2023-08-09]. https://doi.org/10.1016/B978-008055232-3.60818-9.
20	BAJORIN D F, WITJES J A, GSCHWEND J E, et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma[J]. N Engl J Med, 2021, 384(22): 2102-2114.
21	SARFRAZ M, QAMAR S, REHMAN M U, et al. Nano-formulation based intravesical drug delivery systems: an overview of versatile approaches to improve urinary bladder diseases[J]. Pharmaceutics, 2022, 14(9): 1909.
22	VAN DER HEIJDEN M S, LORIOT Y, DURÁN I, et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma: a long-term overall survival and safety update from the phase 3 IMvigor211 clinical trial[J]. Eur Urol, 2021, 80(1): 7-11.
23	DONIN N M, LENIS A T, HOLDEN S, et al. Immunotherapy for the treatment of urothelial carcinoma[J]. J Urol, 2017, 197(1): 14-22.
24	LI Q, LIU Y, HUANG Z, et al. Triggering immune system with nanomaterials for cancer immunotherapy[J]. Front Bioeng Biotechnol, 2022, 10: 878524.
25	SHARMA P, RETZ M, SIEFKER-RADTKE A, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial[J]. Lancet Oncol, 2017, 18(3): 312-322.
26	POWLES T, O'DONNELL P H, MASSARD C, et al. Efficacy and safety of durvalumab in locally advanced or metastatic urothelial carcinoma: updated results from a phase 1/2 open-label study[J]. JAMA Oncol, 2017, 3(9): e172411.
27	APOLO A B, INFANTE J R, BALMANOUKIAN A, et al. Avelumab, an anti-programmed death-ligand 1 antibody, in patients with refractory metastatic urothelial carcinoma: results from a multicenter, phase Ⅰb study[J]. J Clin Oncol, 2017, 35(19): 2117-2124.
28	PREDINA J, ERUSLANOV E, JUDY B, et al. Changes in the local tumor microenvironment in recurrent cancers may explain the failure of vaccines after surgery[J]. Proc Natl Acad Sci U S A, 2013, 110(5): E415-E424.
29	MILLING L, ZHANG Y, IRVINE D J. Delivering safer immunotherapies for cancer[J]. Adv Drug Deliv Rev, 2017, 114: 79-101.
30	LORIOT Y, NECCHI A, PARK S H, et al. Erdafitinib in locally advanced or metastatic urothelial carcinoma[J]. N Engl J Med, 2019, 381(4): 338-348.
31	ROBINSON B D, VLACHOSTERGIOS P J, BHINDER B, et al. Upper tract urothelial carcinoma has a luminal-papillary T-cell depleted contexture and activated FGFR3 signaling[J]. Nat Commun, 2019, 10(1): 2977.
32	SHENG X, YAN X, WANG L, et al. Open-label, multicenter, phase Ⅱ study of RC48-ADC, a HER2-targeting antibody-drug conjugate, in patients with locally advanced or metastatic urothelial carcinoma[J]. Clin Cancer Res, 2021, 27(1): 43-51.
33	SARFATY M, ROSENBERG J E. Antibody-drug conjugates in urothelial carcinomas[J]. Curr Oncol Rep, 2020, 22(2): 13.
34	ROSENBERG J E, O'DONNELL P H, BALAR A V, et al. Pivotal trial of enfortumab vedotin in urothelial carcinoma after platinum and anti-programmed death 1/programmed death ligand 1 therapy[J]. J Clin Oncol, 2019, 37(29): 2592-2600.
35	HU H, FENG W, QIAN X, et al. Emerging nanomedicine-enabled/enhanced nanodynamic therapies beyond traditional photodynamics[J]. Adv Mater, 2021, 33(12): e2005062.
36	INOUE K. 5-Aminolevulinic acid-mediated photodynamic therapy for bladder cancer[J]. Int J Urol, 2017, 24(2): 97-101.
37	DIAMOND I, MCDONAGH A, WILSON C, et al. Photodynamic therapy of malignant tumours[J]. Lancet, 1972, 300(7788): 1175-1177.
38	LEE J Y, DIAZ R R, CHO K S, et al. Efficacy and safety of photodynamic therapy for recurrent, high grade nonmuscle invasive bladder cancer refractory or intolerant to bacille Calmette-Guérin immunotherapy[J]. J Urol, 2013, 190(4): 1192-1199.
39	XIONG W, QI L, JIANG N, et al. Metformin liposome-mediated PD-L1 downregulation for amplifying the photodynamic immunotherapy efficacy[J]. ACS Appl Mater Interfaces, 2021, 13(7): 8026-8041.
40	WANG L, YANG D, LV J Y, et al. Application of carbon nanoparticles in lymph node dissection and parathyroid protection during thyroid cancer surgeries: a systematic review and meta-analysis[J]. Onco Targets Ther, 2017, 10: 1247-1260.
41	SHI J J, KANTOFF P W, WOOSTER R, et al. Cancer nanomedicine: progress, challenges and opportunities[J]. Nat Rev Cancer, 2017, 17(1): 20-37.
42	MATSUMURA Y, MAEDA H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs[J]. Cancer Res, 1986, 46(12 Pt 1): 6387-6392.
43	MI P, CABRAL H, KATAOKA K. Ligand-installed nanocarriers toward precision therapy[J]. Adv Mater, 2020, 32(13): e1902604.
44	GERLOWSKI L E, JAIN R K. Microvascular permeability of normal and neoplastic tissues[J]. Microvasc Res, 1986, 31(3): 288-305.
45	KULKARNI A, CHANDRASEKAR V, NATARAJAN S K, et al. A designer self-assembled supramolecule amplifies macrophage immune responses against aggressive cancer[J]. Nat Biomed Eng, 2018, 2(8): 589-599.
46	DE LA TORRE P, PÉREZ-LORENZO M J, ALCÁZAR-GARRIDO Á, et al. Cell-based nanoparticles delivery systems for targeted cancer therapy: lessons from anti-angiogenesis treatments[J]. Molecules, 2020, 25(3): 715.
47	LI X, CHEN L, LUAN S, et al. The development and progress of nanomedicine for esophageal cancer diagnosis and treatment[J]. Semin Cancer Biol, 2022, 86(Pt 2): 873-885.
48	XU X, LIU K, JIAO B, et al. Mucoadhesive nanoparticles based on ROS activated gambogic acid prodrug for safe and efficient intravesical instillation chemotherapy of bladder cancer[J]. J Control Release, 2020, 324: 493-504.
49	ZHENG B, LIU Z, WANG H, et al. R11 modified tumor cell membrane nanovesicle-camouflaged nanoparticles with enhanced targeting and mucus-penetrating efficiency for intravesical chemotherapy for bladder cancer[J]. J Control Release, 2022, 351: 834-846.
50	MULLAPUDI S S, RAHMAT J N, MAHENDRAN R, et al. Tumor-targeting albumin nanoparticles as an efficacious drug delivery system and potential diagnostic tool in non-muscle-invasive bladder cancer therapy[J]. Nanomedicine, 2022, 46: 102600.
51	AKGÜL A, AHMED N, RAZA A, et al. A fractal fractional model for cervical cancer due to human papillomavirus infection[J]. Fractals, 2021, 29(5): 2140015.
52	SPRANGER S, GAJEWSKI T F. Impact of oncogenic pathways on evasion of antitumour immune responses[J]. Nat Rev Cancer, 2018, 18(3): 139-147.
53	SHARMA P, HU-LIESKOVAN S, WARGO J A, et al. Primary, adaptive, and acquired resistance to cancer immunotherapy[J]. Cell, 2017, 168(4): 707-723.
54	KLEMM F, MAAS R R, BOWMAN R L, et al. Interrogation of the microenvironmental landscape in brain tumors reveals disease-specific alterations of immune cells[J]. Cell, 2020, 181(7): 1643-1660.e17.
55	TERÁN-NAVARRO H, ZEOLI A, SALINES-CUEVAS D, et al. Gold glyconanoparticles combined with 91‒99 peptide of the bacterial toxin, listeriolysin O, are efficient immunotherapies in experimental bladder tumors[J]. Cancers (Basel), 2022, 14(10): 2413.
56	HUNTER B A, EUSTACE A, IRLAM J J, et al. Expression of hypoxia-inducible factor-1α predicts benefit from hypoxia modification in invasive bladder cancer[J]. Br J Cancer, 2014, 111(3): 437-443.
57	MARTINEZ-OUTSCHOORN U E, LIN Z, TRIMMER C, et al. Cancer cells metabolically "fertilize" the tumor microenvironment with hydrogen peroxide, driving the Warburg effect: implications for PET imaging of human tumors[J]. Cell Cycle, 2011, 10(15): 2504-2520.
58	LIN T, ZHAO X, ZHAO S, et al. O₂-generating MnO₂ nanoparticles for enhanced photodynamic therapy of bladder cancer by ameliorating hypoxia[J]. Theranostics, 2018, 8(4): 990-1004.
59	YU C, ZHANG Y, WANG N, et al. Treatment of bladder cancer by geoinspired synthetic chrysotile nanocarrier-delivered circPRMT5 siRNA[J]. Biomater Res, 2022, 26(1): 6.
60	CHEN Y, GAO D Y, HUANG L. In vivo delivery of miRNAs for cancer therapy: challenges and strategies[J]. Adv Drug Deliv Rev, 2015, 81: 128-141.
61	SHEN H, SUN T, FERRARI M. Nanovector delivery of siRNA for cancer therapy[J]. Cancer Gene Ther, 2012, 19(6): 367-373.
62	SHAHIDI M, ABAZARI O, DAYATI P, et al. Multicomponent siRNA/miRNA-loaded modified mesoporous silica nanoparticles targeted bladder cancer for a highly effective combination therapy[J]. Front Bioeng Biotechnol, 2022, 10: 949704.
63	ZHANG L, WAN S S, LI C X, et al. An adenosine triphosphate-responsive autocatalytic Fenton nanoparticle for tumor ablation with self-supplied H₂O₂ and acceleration of Fe³⁺/Fe²⁺ conversion[J]. Nano Lett, 2018, 18(12): 7609-7618.
64	TANG Z, ZHANG H, LIU Y, et al. Antiferromagnetic pyrite as the tumor microenvironment-mediated nanoplatform for self-enhanced tumor imaging and therapy[J]. Adv Mater, 2017, 29(47). doi: 10.1002/adma.201701683.
65	CHEN W H, YU K J, JHOU J W, et al. Glucose/glutathione Co-triggered tumor hypoxia relief and chemodynamic therapy to enhance photothermal therapy in bladder cancer[J]. ACS Appl Bio Mater, 2021, 4(10): 7485-7496.

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基于纳米技术的膀胱癌治疗方法研究进展

Research progress in the treatment of bladder cancer based on nanotechnology

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