目的 探究光热与基因联合治疗递送系统后续的酶降解过程。方法 用肽脂质包覆碳纳米管构建光热/基因联合治疗递送载体单壁碳纳米管-肽脂质复合载体(CDO/SCNT)和多壁碳纳米管-肽脂质复合载体(CDO/MCNT)。采用热重分析考察递送载体的结合程度。使用辣根过氧化物酶(HRP)体外模拟酶环境,通过拉曼光谱和透射电子显微镜观察递送载体的酶降解性能。结果 CDO/SCNT中SCNT占38.5%,CDO/MCNT中MCNT占34.2%,肽脂质成功包覆在碳纳米管表面。载体在酶环境下7 d就发生降解,28 d时,拉曼光谱可见CDO/SCNT载体D带的结晶结构紊乱程度与G带的E2g振动信号峰强度比值达到0.48,而未包覆肽脂质层的SCNT达到0.31;透射电镜观察到2种递送载体中碳纳米管破碎;CDO/SCNT的酶降解程度要高于CDO/MCNT。结论 HRP酶可催化H2O2氧化石墨结构生成CO2,肽脂质层有助于碳纳米管(CNTs)的酶降解,CDO/SCNT载体具有良好的酶降解性能。
Abstract
OBJECTIVE To explore the enzyme degradation mechanism of the combined therapy delivery system of photothermal and gene therapy. METHODS Herein, cationic lipids were used to coat single-walled carbon nanotubes (SCNT) and multi-walled carbon nanotubes (MCNT) to form delivery systems (denoted CDO/SCNT and CDO/MCNT). The results of thermos gravimetric analysis showed that the lipid layer was successfully coated on the surface of carbon nanotubes. Horseradish peroxidase (HRP) was used to simulate the enzyme environment in vitro to investigate the enzyme degradation performance of the delivery carrier. RESULTS The integrity of the graphite structure in the carbon nanotubes was observed by Raman spectroscopy and TEM on day 0, with the extension of degradation time, the degradation degree of carbon nanotubes gradually increased within 28 days. The ratio of the disordered crystal structure of the D band of CDO/SCNT carrier to the E2g vibration signal intensity of the G band reached 0.48, while the SCNT of the uncoated lipid layer reached 0.31. The fragmentation of carbon nanotubes boththe two delivery carrier was also observed using TEM, and the degree of enzyme degradation of CDO/SCNT delivery carrier was higher than that of CDO/MCNT. CONCLUSION Thus, the HRP can catalyze the degradation of carbon nanotubes by H2O2, oxidize the graphite structure to form CO2, and the peptide lipid layer contributes to the enzymatic degradation of CNTs.
关键词
碳纳米管 /
肽脂质 /
递送系统 /
酶降解
{{custom_keyword}} /
Key words
carbon nanotube /
peptide lipid /
delivery system /
enzymatic degradation
{{custom_keyword}} /
中图分类号:
R944
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[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 . CA A Cancer J Clin, 2021, 71(3):1-41.
[2] NIA H T, MUNN L L, JAIN P K, et al. Physical traits of cancer . Science, 2020, 370(6516):543-545.
[3] CAVAZZANA-CALYO M, THRASHER A, MAVILIO F. The future of gene therapy . Nature, 2004, 427(6977):779-781.
[4] MELAMED J R, EDELSTEIN R S, DAY E S. Elucidating the fundamental mechanisms of cell death triggered by photothermal therapy . ACS Nano, 2015, 9(1):6-11.
[5] ZHANG S H, SUN C X, ZENG J F, et al. Ambient aqueous synthesis of ultrasmall PEGylated Cu2-xSe nanoparticles as a multifunctional theranostic agent for multimodal imaging guided photothermal therapy of cancer . Adv Mater, 2016, 28(40):8927-8936.
[6] GUO W, GUO C, ZHENG N, et al. CsxWO3 nanorods coated with polyelectrolyte multilayers as a multifunctional nano-material for bimodal imaging-guided photothermal/photodynamic cancer treatment . Adv Mater, 2017, 29(4):1-9.
[7] ANDREW F, XU S, MONTGOMERY M K, et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans . Nature, 1998, 391(6669):744-745.
[8] SHEN S, DEAN D C, YU Z, et al. Aberrant CDK9 expression within Chordoma tissues and the therapeutic potential of a selective CDK9 inhibitor LDC000067 . J Cancer, 2020, 11(1):132-141.
[9] LIU Z, SUN X, NAKAYAMA-RATCHFORD N, et al. Supramolecular chemistry on water-soluble carbon nanotubes for drug loading and delivery . ACS Nano, 2007, 1(1):50-56.
[10] DHAR S, LIU Z, THOMALE J, et al. Targeted single-wall carbon nanotube-mediated Pt (Ⅳ) prodrug delivery using folate as a homing device . J Am Chem Soc, 2008, 130(34):11467-11476.
[11] ANZAR N, HASAN R, TYAGI M, et al. Carbon nanotube-a review on synthesis, properties and plethora of applications in the field of biomedical science. Sens Int, 2020, 1: Doi: 10.1016/j.sintl.2020.100003.
[12] SIREESHA M, BABU J V, KIRAN K S A, et al. A review on carbon nanotubes in biosensor devices and their applications in medicine . Nanocomposites, 2018, 4(2):36-57.
[13] ZHAO Y N, ZHAO T Y, CAO Y N, et al. Temperature-sensitive lipid-coated carbon nanotubes for synergistic photothermal therapy and gene therapy . ACS Nano, 2021, 15(4):6517-6529.
[14] ALLEN B, KICHAMBARE P D, GUO P P, et al. Biodegradation of single-walled carbon nanotubes through enzymatic catalysis . Nano Lett, 2008, 8(11):3899-3903.
[15] DAI W Q, WANG D Z. Cutting methods and perspectives of carbon nanotubes . J Phys Chem C, 2021, 125(18):9593-9617.
[16] WANG L, SHI J, ZHANG H, et al. Synergistic anticancer effect of RNAi and photothermal therapy mediated by functionalized single-walled carbon nanotubes . Biomaterials, 2013, 34(1):262-274.
[17] KAGAN V E, KONDURU N V, FENG W, et al. Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation . Nat Nanotechnol, 2010, 5(5):354-359.
[18] KOTCHEY G P, HASAN S A, KAPRALOV A A, et al. A natural vanishing act: the enzyme-catalyzed degradation of carbon nanomaterials . Acc Chem Res, 2012, 45(10):1770-1781.
[19] KOTCHEY G P, ZHAO Y, KAGAN V E, et al. Peroxidase-mediated biodegradation of carbon nanotubes in vitro and in vivo . Adv Drug Deliv Rev, 2013, 65(15):1921-1932.
[20] SCHREINER K M, FILLEY T R, BLANCHETTE R A, et al. White-rot basidiomycete-mediated decomposition of C60 Fullerol . Environ Sci Technol, 2009, 43(9):3162-3168.
[21] LEE J, CHO M, FORTHER J D, HUGHES J B, et al. Transformation of aggregated C60 in the aqueous phase by UV irradiation . Environ Sci Technol, 2009, 43(13):4878-4883.
[22] BAI H, JIANG W, KOTCHEY G P, et al. Insight into the mechanism of graphene oxide degradation via the photo-fenton reaction . J Phys Chem C, 2014, 118(19):10519-10529.
[23] CHANDRASEKARAN G, CHOI SK, LEE YC, et al. Oxidative biodegradation of single-walled carbon nanotubes by partially purified lignin peroxidase from Sparassis latifolia mushroom . J Ind Eng Chem, 2014, 20(5):3367-3374
[24] ZHOU L B. Development of mesoporous carbon nanospheres for photoacoustic imaging and chemo-photothermal cancer therapy. Changchun: Jilin University, 2018.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
国家自然科学基金项目资助(21776044;21606041);校级大学生创新创业训练计划项目资助(202112026214;202112026168)
{{custom_fund}}