纳米载药系统在肝癌治疗中的研究进展

王淼东; 陈泽山; 彭佩纯; 邓鑫

doi:10.3969/j.issn.1001-5256.2022.08.037

纳米载药系统在肝癌治疗中的研究进展

DOI: 10.3969/j.issn.1001-5256.2022.08.037

王淼东^a,
陈泽山^a,
彭佩纯^a,
邓鑫^b, , ,

a.
广西中医药大学研究生院，南宁 530000
b.
广西中医药大学基础医学院，南宁 530000

基金项目:

广西科技计划项目 (guikeAB20297002);

广西中医药大学研究生教育创新计划项目 (YCBXJ2022021)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：王淼东负责课题设计并撰写论文；陈泽山、彭佩纯参与收集数据，修改论文；邓鑫负责指导撰写论文并最后定稿。

详细信息

通信作者:
邓鑫，dx8848@126.com

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出版历程
- 收稿日期: 2022-02-27
- 录用日期: 2022-04-11
- 出版日期: 2022-08-20

Research advances in nano-drug delivery system in liver cancer treatment

a.
Graduate School, Guangxi University of Chinese Medicine, Nanning 530000, China
b.
School of Basic Medical Sciences, Guangxi University of Chinese Medicine, Nanning 530000, China

Research funding:

Guangxi Science and Technology Project (guikeAB20297002);

Innovation Project of Guangxi Graduate Education of GXUCM (YCBXJ2022021)

More Information

Corresponding author: DENG Xin, dx8848@126.com(ORCID:0000-0001-6835-7901)

摘要

摘要: 传统手术切除、放疗、化疗在肝癌治疗中占据主导地位。然而，化疗药物的毒副作用、疗效不稳定以及靶点不明确常限制了其在肝癌患者中的应用。因此，为了提高药物在肝癌治疗中的疗效，近些年在生物医学领域发展起来的纳米医学进入了人们的视野。纳米载药系统以低毒、生物利用度广、药物释放可控、稳定性好等优势被逐渐应用于临床研究，本文将着重介绍纳米载药系统在肝癌治疗中的最新进展。
- 肝肿瘤 /
- 纳米载药系统 /
- 治疗学
Abstract: Traditional surgical resection, radiotherapy, and chemotherapy still play a dominant role in the treatment of liver cancer; however, their application in liver cancer patients is often limited by the toxic and side effects, unstable efficacy, and unclear targets of chemotherapeutic drugs. Therefore, in order to improve the efficacy of drugs in the treatment of liver cancer, nanomedicine, which has been developed in the biomedical field in recent years, has attracted more and more attention. Nano-drug delivery system has been gradually applied in clinical research for its advantages of low toxicity, wide bioavailability, controllable drug release, and good stability. This article focuses on the latest research advances in nano-drug delivery system in the treatment of liver cancer.
- Liver Neoplasms /
- Nano Drug Delivery System /
- Therapeutics

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参考文献(49)

[1]	WU T, CHEN L. New progress in precision diagnosis and treatment of liver cancer[J]. J Clin Hepatol, 2022, 38(3): 497-498. DOI: 10.3969/j.issn.1001-5256.2022.03.001. 吴彤, 陈磊. 肝癌精准诊疗新进展[J]. 临床肝胆病杂志, 2022, 38(3): 497-498. DOI: 10.3969/j.issn.1001-5256.2022.03.001.
[2]	FU J, WANG H. Precision diagnosis and treatment of liver cancer in China[J]. Cancer Lett, 2018, 412: 283-288. DOI: 10.1016/j.canlet.2017.10.008.
[3]	YANG JD, HAINAUT P, GORES GJ, et al. A global view of hepatocellular carcinoma: trends, risk, prevention and management[J]. Nat Rev Gastroenterol Hepatol, 2019, 16(10): 589-604. DOI: 10.1038/s41575-019-0186-y.
[4]	BERTRAND N, WU J, XU X, et al. Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology[J]. Adv Drug Deliv Rev, 2014, 66: 2-25. DOI: 10.1016/j.addr.2013.11.009.
[5]	ZHANG LM, TIAN Y, LI Q. Antitumor effect of shikonin loaded milk derived exosomes on hepatoma cells[J]. Chin J Dig Surg, 2021, 20(12): 1313-1317. DOI: 10.3760/cma.j.cn115610-20211111-00557. 张礼萌, 田野, 李强. 牛乳-紫草素纳米载药体系对肝癌细胞的杀伤作用研究[J]. 中华消化外科杂志, 2021, 20(12): 1313-1317. DOI: 10.3760/cma.j.cn115610-20211111-00557.
[6]	ZHANG YN, POON W, TAVARES AJ, et al. Nanoparticle-liver interactions: Cellular uptake and hepatobiliary elimination[J]. J Control Release, 2016, 240: 332-348. DOI: 10.1016/j.jconrel.2016.01.020.
[7]	KUMARI P, GHOSH B, BISWAS S. Nanocarriers for cancer-targeted drug delivery[J]. J Drug Target, 2016, 24(3): 179-191. DOI: 10.3109/1061186X.2015.1051049.
[8]	DANHIER F. To exploit the tumor microenvironment: Since the EPR effect fails in the clinic, what is the future of nanomedicine?[J]. J Control Release, 2016, 244(Pt A): 108-121. DOI: 10.1016/j.jconrel.2016.11.015.
[9]	KANG H, RHO S, STILES WR, et al. Size-dependent EPR effect of polymeric nanoparticles on tumor targeting[J]. Adv Healthc Mater, 2020, 9(1): e1901223. DOI: 10.1002/adhm.201901223.
[10]	ROSENBLUM D, JOSHI N, TAO W, et al. Progress and challenges towards targeted delivery of cancer therapeutics[J]. Nat Commun, 2018, 9(1): 1410. DOI: 10.1038/s41467-018-03705-y.
[11]	BAR-ZEEV M, LIVNEY YD, ASSARAF YG. Targeted nanomedicine for cancer therapeutics: Towards precision medicine overcoming drug resistance[J]. Drug Resist Updat, 2017, 31: 15-30. DOI: 10.1016/j.drup.2017.05.002.
[12]	ZHANG Y, CAO J, YUAN Z. Strategies and challenges to improve the performance of tumor-associated active targeting[J]. J Mater Chem B, 2020, 8(18): 3959-3971. DOI: 10.1039/d0tb00289e.
[13]	ELNAGGAR MH, ABUSHOUK AI, HASSAN A, et al. Nanomedicine as a putative approach for active targeting of hepatocellular carcinoma[J]. Semin Cancer Biol, 2021, 69: 91-99. DOI: 10.1016/j.semcancer.2019.08.016.
[14]	LIU G, LOVELL JF, ZHANG L, et al. Stimulus-responsive nanomedicines for disease diagnosis and treatment[J]. Int J Mol Sci, 2020, 21(17): 6380. DOI: 10.3390/ijms21176380.
[15]	ZAHEDNEZHAD F, SAADAT M, VALIZADEH H, et al. Liposome and immune system interplay: Challenges and potentials[J]. J Control Release, 2019, 305: 194-209. DOI: 10.1016/j.jconrel.2019.05.030.
[16]	YE H, ZHOU L, JIN H, et al. Sorafenib-loaded long-circulating nanoliposomes for liver cancer therapy[J]. Biomed Res Int, 2020, 2020: 1351046. DOI: 10.1155/2020/1351046.
[17]	LU XY, WU DC, LI ZJ, et al. Polymer nanoparticles[J]. Prog Mol Biol Transl Sci, 2011, 104: 299-323. DOI: 10.1016/B978-0-12-416020-0.00007-3.
[18]	JIANG L, WANG Y, WEI X, et al. Improvement in phenotype homeostasis of macrophages by chitosan nanoparticles and subsequent impacts on liver injury and tumor treatment[J]. Carbohydr Polym, 2022, 277: 118891. DOI: 10.1016/j.carbpol.2021.118891.
[19]	ELZAYAT A, ADAM-CERVERA I, ÁLVAREZ-BERM ÚDEZ O, et al. Nanoemulsions for synthesis of biomedical nanocarriers[J]. Colloids Surf B Biointerfaces, 2021, 203: 111764. DOI: 10.1016/j.colsurfb.2021.111764.
[20]	JI G, MA L, YAO H, et al. Precise delivery of obeticholic acid via nanoapproach for triggering natural killer T cell-mediated liver cancer immunotherapy[J]. Acta Pharm Sin B, 2020, 10(11): 2171-2182. DOI: 10.1016/j.apsb.2020.09.004.
[21]	YANG G, PHUA S, BINDRA AK, et al. Degradability and clearance of inorganic nanoparticles for biomedical applications[J]. Adv Mater, 2019, 31(10): e1805730. DOI: 10.1002/adma.201805730.
[22]	TAGHIZADEH S, ALIMARDANI V, ROUDBALI PL, et al. Gold nanoparticles application in liver cancer[J]. Photodiagnosis Photodyn Ther, 2019, 25: 389-400. DOI: 10.1016/j.pdpdt.2019.01.027.
[23]	CAI H, YANG Y, PENG F, et al. Gold nanoparticles-loaded anti-miR221 enhances antitumor effect of sorafenib in hepatocellular carcinoma cells[J]. Int J Med Sci, 2019, 16(12): 1541-1548. DOI: 10.7150/ijms.37427.
[24]	CHEN L, LIU J, ZHANG Y, et al. The toxicity of silica nanoparticles to the immune system[J]. Nanomedicine (Lond), 2018, 13(15): 1939-1962. DOI: 10.2217/nnm-2018-0076.
[25]	CHANG D, GAO Y, WANG L, et al. Polydopamine-based surface modification of mesoporous silica nanoparticles as pH-sensitive drug delivery vehicles for cancer therapy[J]. J Colloid Interface Sci, 2016, 463: 279-287. DOI: 10.1016/j.jcis.2015.11.001.
[26]	YUE J, LUO SZ, LU MM, et al. A comparison of mesoporous silica nanoparticles and mesoporous organosilica nanoparticles as drug vehicles for cancer therapy[J]. Chem Biol Drug Des, 2018, 92(2): 1435-1444. DOI: 10.1111/cbdd.13309.
[27]	LIU YY, CHANG BM, CHANG HC. Nanodiamond-enabled biomedical imaging[J]. Nanomedicine (Lond), 2020, 15(16): 1599-1616. DOI: 10.2217/nnm-2020-0091.
[28]	FARRA R, GRASSI M, GRASSI G, et al. Therapeutic potential of small interfering RNAs/micro interfering RNA in hepatocellular carcinoma[J]. World J Gastroenterol, 2015, 21(30): 8994-9001. DOI: 10.3748/wjg.v21.i30.8994.
[29]	XU J, GU M, HOOI L, et al. Enhanced penetrative siRNA delivery by a nanodiamond drug delivery platform against hepatocellular carcinoma 3D models[J]. Nanoscale, 2021, 13(38): 16131-16145. DOI: 10.1039/d1nr03502a.
[30]	SHAO YM, ZHANG Y, YIN X. et al. Value of Sal-like 4 in the diagnosis and treatment of primary liver cancer[J]. J Clin Hepatol, 2019, 35(10): 2320-2323. DOI: 10.3969/j.issn.1001-5256.2019.10.041. 邵玥明, 张雨, 殷鑫, 等. SALL4在原发性肝癌诊治中的价值[J]. 临床肝胆病杂志, 2019, 35(10): 2320-2323. DOI: 10.3969/j.issn.1001-5256.2019.10.041.
[31]	MOHANTY A, UTHAMAN S, PARK IK. Utilization of polymer-lipid hybrid nanoparticles for targeted anti-cancer therapy[J]. Molecules, 2020, 25(19): 4377. DOI: 10.3390/molecules25194377.
[32]	ZHANG J, HU J, CHAN HF, et al. iRGD decorated lipid-polymer hybrid nanoparticles for targeted co-delivery of doxorubicin and sorafenib to enhance anti-hepatocellular carcinoma efficacy[J]. Nanomedicine, 2016, 12(5): 1303-1311. DOI: 10.1016/j.nano.2016.01.017.
[33]	GILIOPOULOS D, ZAMBOULIS A, GIANNAKOUDAKIS D, et al. Polymer/Metal Organic Framework (MOF) nanocomposites for biomedical applications[J]. Molecules, 2020, 25(1): 185. DOI: 10.3390/molecules25010185.
[34]	FYTORY M, ARAFA KK, EL ROUBY W, et al. Dual-ligated metal organic framework as novel multifunctional nanovehicle for targeted drug delivery for hepatic cancer treatment[J]. Sci Rep, 2021, 11(1): 19808. DOI: 10.1038/s41598-021-99407-5.
[35]	CHEN L, HONG W, REN W, et al. Recent progress in targeted delivery vectors based on biomimetic nanoparticles[J]. Signal Transduct Target Ther, 2021, 6(1): 225. DOI: 10.1038/s41392-021-00631-2.
[36]	XIA Q, ZHANG Y, LI Z, et al. Red blood cell membrane-camouflaged nanoparticles: a novel drug delivery system for antitumor application[J]. Acta Pharm Sin B, 2019, 9(4): 675-689. DOI: 10.1016/j.apsb.2019.01.011.
[37]	KONG D, JIANG T, LIU J, et al. Chemoembolizing hepatocellular carcinoma with microsphere cored with arsenic trioxide microcrystal[J]. Drug Deliv, 2020, 27(1): 1729-1740. DOI: 10.1080/10717544.2020.1856219.
[38]	LIAN Y, WANG X, GUO P, et al. Erythrocyte membrane-coated arsenic trioxide-loaded sodium alginate nanoparticles for tumor therapy[J]. Pharmaceutics, 2019, 12(1): 21. DOI: 10.3390/pharmaceutics12010021.
[39]	JAILLON S, PONZETTA A, DI MITRI D, et al. Neutrophil diversity and plasticity in tumour progression and therapy[J]. Nat Rev Cancer, 2020, 20(9): 485-503. DOI: 10.1038/s41568-020-0281-y.
[40]	ZHANG Z, LI D, CAO Y, et al. Biodegradable Hypocrellin B nanoparticles coated with neutrophil membranes for hepatocellular carcinoma photodynamics therapy effectively via JUNB/ROS signaling[J]. Int Immunopharmacol, 2021, 99: 107624. DOI: 10.1016/j.intimp.2021.107624.
[41]	HUANG AC, POSTOW MA, ORLOWSKI RJ, et al. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response[J]. Nature, 2017, 545(7652): 60-65. DOI: 10.1038/nature22079.
[42]	SHEN N, WU J, YANG C, et al. Combretastatin A4 nanoparticles combined with hypoxia-sensitive imiquimod: a new paradigm for the modulation of host immunological responses during cancer treatment[J]. Nano Lett, 2019, 19(11): 8021-8031. DOI: 10.1021/acs.nanolett.9b03214.
[43]	VORON T, COLUSSI O, MARCHETEAU E, et al. VEGF-A modulates expression of inhibitory checkpoints on CD8⁺ T cells in tumors[J]. J Exp Med, 2015, 212(2): 139-148. DOI: 10.1084/jem.20140559.
[44]	BAO X, SHEN N, LOU Y, et al. Enhanced anti-PD-1 therapy in hepatocellular carcinoma by tumor vascular disruption and normalization dependent on combretastatin A4 nanoparticles and DC101[J]. Theranostics, 2021, 11(12): 5955-5969. DOI: 10.7150/thno.58164.
[45]	LI H, SHI S, WU M, et al. iRGD peptide-mediated liposomal nanoparticles with photoacoustic/ultrasound dual-modality imaging for precision theranostics against hepatocellular carcinoma[J]. Int J Nanomedicine, 2021, 16: 6455-6475. DOI: 10.2147/IJN.S325891.
[46]	LI S, YIN G, PU X, et al. A novel tumor-targeted thermosensitive liposomal cerasome used for thermally controlled drug release[J]. Int J Pharm, 2019, 570: 118660. DOI: 10.1016/j.ijpharm.2019.118660.
[47]	LYON PC, GRAY MD, MANNARIS C, et al. Safety and feasibility of ultrasound-triggered targeted drug delivery of doxorubicin from thermosensitive liposomes in liver tumours (TARDOX): a single-centre, open-label, phase 1 trial[J]. Lancet Oncol, 2018, 19(8): 1027-1039. DOI: 10.1016/S1470-2045(18)30332-2.
[48]	HASHIMOTO A, SARKER D, REEBYE V, et al. Upregulation of C/EBPα inhibits suppressive activity of myeloid cells and potentiates antitumor response in mice and patients with cancer[J]. Clin Cancer Res, 2021, 27(21): 5961-5978. DOI: 10.1158/1078-0432.CCR-21-0986.
[49]	SARKER D, PLUMMER R, MEYER T, et al. MTL-CEBPA, a small activating RNA therapeutic upregulating C/EBP-α, in patients with advanced liver cancer: a first-in-human, multicenter, open-label, phase I trial[J]. Clin Cancer Res, 2020, 26(15): 3936-3946. DOI: 10.1158/1078-0432.CCR-20-0414.