Биоминерализация геномной ДНК человека в цеолитоподобный металлоорганический каркасный полимер ZIF-8

И.Х. Шайхутдинов, П.В. Ильясов, Л.В. Лимарева, А.С. Сустретов, Д.А. Кокорев, А.В. Соколов

Ключевые слова: биоминерализация; инкапсуляция; металлоорганические каркасные полимеры; геномная ДНК человека; генетические векторы; полимер ZIF-8.

2024, том 16, номер 1, стр. 5.

DOI: https://doi.org/10.17691/stm2024.16.1.01

Полный текст статьи

html pdf

1077

1087

Аннотация
Список литературы
Как цитировать в References

Цель исследования — оценить возможности биоминерализации геномной ДНК человека в металлоорганический каркасный полимер (МОКП) ZIF-8 и сохранения включенной последовательности ДНК после цикла инкапсуляции и растворения композита. Данное исследование является начальным этапом разработки абиотического вектора для работы с нативными нуклеиновыми кислотами произвольного размера на основе композита ДНК@ZIF-8.

Материалы и методы. Объектом исследования послужила геномная ДНК человека, выделенная из лимфоцитов периферической крови здоровых добровольцев, с использованием набора «Проба-НК» (НПО «ДНК-Технология», Россия). Оценку чистоты и концентрации геномной ДНК проводили спектрофотометрически при длинах волн 260/280 нм на планшет-ридере Tecan Infinity 200 Pro (Tecan Instruments, Австрия). Синтез ZIF-8 выполняли в физиологических условиях (37°С) путем смешивания водных растворов солей цинка с 2-метилимидазолом при различных мольных соотношениях. В аналогичных условиях была проведена биоминерализация геномной ДНК человека в ZIF-8. Полученный МОКП и композит ДНК@ZIF-8 исследовали методом порошковой рентгеновской дифрактометрии на дифрактометре Phaser D2 (Bruker, США), удельную площадь поверхности оценивали на порозиметре Autosorb iQ (Quantachrome, США). Для количественной оценки инкапсулированной ДНК композит ДНК@ZIF-8 растворяли в цитратном буфере. Сохранность ДНК определяли методом аллель-специфической ПЦР в режиме реального времени (АС-ПЦР) с использованием наборов для исследования однонуклеотидных полиморфизмов (НПФ «Литех», Россия) на амплификаторе Quantstudio 6 Pro (Thermo Scientific, США). В случае использования наборов с электрофоретической детекцией амплификацию проводили на термоциклере T100 (Thermo Scientific, США).

Результаты. Получены полимер ZIF-8 и композит ДНК@ZIF-8 при различных мольных соотношениях ионов цинка с 2-метилимидазолом, охарактеризована их структура и удельная площадь поверхности. Определена эффективность биоминерализации геномной ДНК, которая составила порядка 7–8%. ПЦР-анализ биоминерализованной ДНК показал сохранность неселективно выбранных локусов.

Заключение. В результате исследований подтверждена возможность инкапсуляции геномной ДНК в металлоорганический каркасный полимер ZIF-8. ДНК после биоминерализации сохраняет пригодность для использования в исследованиях по формированию и изучению генетических конструктов.

Gardlík R., Pálffy R., Hodosy J., Lukács J., Turna J., Celec P. Vectors and delivery systems in gene therapy. Med Sci Monit 2005; 11(4): RA110–RA121,
Flitsch L.J., Börner K., Stüllein C., Ziegler S., Sonntag-Buck V., Wiedtke E., Semkova V., Au Yeung S.W.C., Schlee J., Hajo M., Mathews M., Ludwig B.S., Kossatz S., Kessler H., Grimm D., Brüstle O. Identification of adeno-associated virus variants for gene transfer into human neural cell types by parallel capsid screening. Sci Rep 2022; 12(1): 8356, https://doi.org/10.1038/s41598-022-12404-0.
Franceschi R.T., Ge C. Gene delivery by adenoviruses. In: Methods in molecular biology. Osteoporosis: methods and protocols. Westendorf J.J. (editor). Totowa, NJ: Humana Press; 2008; p. 137–147.
George L.A., Monahan P.E., Eyster M.E., Sullivan S.K., Ragni M.V., Croteau S.E., Rasko J.E.J., Recht M., Samelson-Jones B.J., MacDougall A., Jaworski K., Noble R., Curran M., Kuranda K., Mingozzi F., Chang T., Reape K.Z., Anguela X.M., High K.A. Multiyear factor VIII expression after AAV gene transfer for hemophilia A. N Engl J Med 2021; 385(21): 1961–1973, https://doi.org/10.1056/nejmoa2104205.
Kohn D.B., Booth C., Kang E.M., Pai S.Y., Shaw K.L., Santilli G., Armant M., Buckland K.F., Choi U., De Ravin S.S., Dorsey M.J., Kuo C.Y., Leon-Rico D., Rivat C., Izotova N., Gilmour K., Snell K., Dip J.X., Darwish J., Morris E.C., Terrazas D., Wang L.D., Bauser C.A., Paprotka T., Kuhns D.B., Gregg J., Raymond H.E., Everett J.K., Honnet G., Biasco L., Newburger P.E., Bushman F.D., Grez M., Gaspar H.B., Williams D.A., Malech H.L., Galy A., Thrasher A.J.; Net4CGD consortium. Lentiviral gene therapy for X-linked chronic granulomatous disease. Nat Med 2020; 26(2): 200–206, https://doi.org/10.1038/s41591-019-0735-5.
Martinez-Navio J.M., Fuchs S.P., Pantry S.N., Lauer W.A., Duggan N.N., Keele B.F., Rakasz E.G., Gao G., Lifson J.D., Desrosiers R.C. Adeno-associated virus delivery of anti-HIV monoclonal antibodies can drive long-term virologic suppression. Immunity 2019; 50(3): 567–75.e5, https://doi.org/10.1016/j.immuni.2019.02.005.
Pavlou M., Schön C., Occelli L.M., Rossi A., Meumann N., Boyd R.F., Bartoe J.T., Siedlecki J., Gerhardt M.J., Babutzka S., Bogedein J., Wagner J.E., Priglinger S.G., Biel M., Petersen-Jones S.M., Büning H., Michalakis S. Novel AAV capsids for intravitreal gene therapy of photoreceptor disorders. EMBO Mol Med 2021; 13(4): e13392, https://doi.org/10.15252/emmm.202013392.
Tolmachov O. Designing plasmid vectors. In: Methods in molecular biology. Gene therapy of cancer: methods and protocols. Walther W., Stein U.S. (editors). Totowa, NJ: Humana Press; 2009. p. 117–129.
Hanlon K.S., Kleinstiver B.P., Garcia S.P., Zaborowski M.P., Volak A., Spirig S.E., Muller A., Sousa A.A., Tsai S.Q., Bengtsson N.E., Lööv C., Ingelsson M., Chamberlain J.S., Corey D.P., Aryee M.J., Joung J.K., Breakefield X.O., Maguire C.A., György B. High levels of AAV vector integration into CRISPR-induced DNA breaks. Nat Commun 2019; 10(1): 4439, https://doi.org/10.1038/s41467-019-12449-2.
Basinska T., Gadzinowski M., Mickiewicz D., Slomkowski S. Functionalized particles designed for targeted delivery. Polymers (Basel) 2021; 13(12): 2022, https://doi.org/10.3390/polym13122022.
Eygeris Y., Gupta M., Kim J., Sahay G. Chemistry of lipid nanoparticles for RNA delivery. Acc Chem Res 2022; 55(1): 2–12, https://doi.org/10.1021/acs.accounts.1c00544.
Mintzer M.A., Simanek E.E. Nonviral vectors for gene delivery. Chem Rev 2009; 109(2): 259–302, https://doi.org/10.1021/cr800409e.
Zhu H., Zhang L., Tong S., Lee C.M., Deshmukh H., Bao G. Spatial control of in vivo CRISPR-Cas9 genome editing via nanomagnets. Nat Biomed Eng 2019; 3(2): 126–136, https://doi.org/10.1038/s41551-018-0318-7.
Feng Q., Liu Y., Huang J., Chen K., Huang J., Xiao K. Uptake, distribution, clearance, and toxicity of iron oxide nanoparticles with different sizes and coatings. Sci Rep 2018; 8(1): 2082, https://doi.org/10.1038/s41598-018-19628-z.
Maier M.A., Jayaraman M., Matsuda S., Liu J., Barros S., Querbes W., Tam Y.K., Ansell S.M., Kumar V., Qin J., Zhang X., Wang Q., Panesar S., Hutabarat R., Carioto M., Hettinger J., Kandasamy P., Butler D., Rajeev K.G., Pang B., Charisse K., Fitzgerald K., Mui B.L., Du X., Cullis P., Madden T.D., Hope M.J., Manoharan M., Akinc A. Biodegradable lipids enabling rapidly eliminated lipid nanoparticles for systemic delivery of RNAi therapeutics. Mol Ther 2013; 21(8): 1570–1578, https://doi.org/10.1038/mt.2013.124.
Schultheis B., Strumberg D., Kuhlmann J., Wolf M., Link K., Seufferlein T., Kaufmann J., Feist M., Gebhardt F., Khan M., Stintzing S., Pelzer U. Safety, efficacy and pharcacokinetics of targeted therapy with the liposomal RNA interference therapeutic Atu027 combined with gemcitabine in patients with pancreatic adenocarcinoma. A randomized phase Ib/IIa study. Cancers (Basel) 2020; 12(11): 3130, https://doi.org/10.3390/cancers12113130.
Yadav S., Sharma A.K., Kumar P. Nanoscale self-assembly for therapeutic delivery. Front Bioeng Biotechnol 2020; 8: 127, https://doi.org/10.3389/fbioe.2020.00127.
Yan Y., Liu X.Y., Lu A., Wang X.Y., Jiang L.X., Wang J.C. Non-viral vectors for RNA delivery. J Control Release 2022; 342: 241–279, https://doi.org/10.1016/j.jconrel.2022.01.008.
Rui Y., Wilson D.R., Choi J., Varanasi M., Sanders K., Karlsson J., Lim M., Green J.J. Carboxylated branched poly(β-amino ester) nanoparticles enable robust cytosolic protein delivery and CRISPR-Cas9 gene editing. Sci Adv 2019; 5(12): eaay3255, https://doi.org/10.1126/sciadv.aay3255.
Poddar A., Conesa J.J., Liang K., Dhakal S., Reineck P., Bryant G., Pereiro E., Ricco R., Amenitsch H., Doonan C., Mulet X., Doherty C.M., Falcaro P., Shukla R. Encapsulation, visualization and expression of genes with biomimetically mineralized zeolitic imidazolate framework-8 (ZIF-8). Small 2019; 15(36): e1902268, https://doi.org/10.1002/smll.201902268.
Jia J., Zhang S., Wen K., Li Q. Nano-scaled zeolitic imidazole framework-8 as an efficient carrier for the intracellular delivery of RNase A in cancer treatment. Int J Nanomedicine 2019; 14: 9971–9981, https://doi.org/10.2147/ijn.s210107.
Teplensky M.H., Fantham M., Poudel C., Hockings C., Lu M., Guna A., Aragones-Anglada M., Moghadam P.Z., Li P., Farha O.K., Bernaldo de Quirós Fernández S., Richards F.M., Jodrell D.I., Kaminski Schierle G., Kaminski C.F., Fairen-Jimenez D. A highly porous metal-organic framework system to deliver payloads for gene knockdown. Chem 2019; 5(11): 2926–2941, https://doi.org/10.1016/j.chempr.2019.08.015.
Shi L., Wu J., Qiao X., Ha Y., Li Y., Peng C., Wu R. In situ biomimetic mineralization on ZIF-8 for smart drug delivery. ACS Biomater Sci Eng 2020; 6(8): 4595–4603, https://doi.org/10.1021/acsbiomaterials.0c00935.
Zhang Y., Lai L., Liu Y., Chen B., Yao J., Zheng P., Pan Q., Zhu W. Biomineralized cascade enzyme-encapsulated ZIF-8 nanoparticles combined with antisense oligonucleotides for drug-resistant bacteria treatment. ACS Appl Mater Interfaces 2022; 14(5): 6453–6464, https://doi.org/10.1021/acsami.1c23808.
Abdelhamid H.N., Dowaidar M., Langel Ü. Carbonized chitosan encapsulated hierarchical porous zeolitic imidazolate frameworks nanoparticles for gene delivery. Microporous Mesoporous Mater 2020; 302: 110200, https://doi.org/10.1016/j.micromeso.2020.110200.
Khalilian S.F., Tohidi M., Rastegari B. Synthesis of a biocompatible nanoporous zeolitic imidazolate framework-8 in the presence of Gum Arabic inspired by the biomineralization process. CrystEngComm 2020; 22(10): 1875–1884, https://doi.org/10.1039/c9ce01915d.
Ren L., Xiao X., Chen Y., Yu Y., Zhang Q., Liu R., Xu W. Preparation of ZIF-8/natural plant fiber composites via biomimetic mineralization for highly efficient removal of formaldehyde. ChemistrySelect 2019; 4(42): 12294–12303, https://doi.org/10.1002/slct.201903234.
Velásquez-Hernández M.J., Astria E., Winkler S., Liang W., Wiltsche H., Poddar A., Shukla R., Prestwich G., Paderi J., Salcedo-Abraira P., Amenitsch H., Horcajada P., Doonan C.J., Falcaro P. Modulation of metal-azolate frameworks for the tunable release of encapsulated glycosaminoglycans. Chem Sci 2020; 11(39): 10835–10843, https://doi.org/10.1039/d0sc01204a.
Li S., Dharmarwardana M., Welch R.P., Ren Y., Thompson C.M., Smaldone R.A., Gassensmith J.J. Template-directed synthesis of porous and protective core-shell bionanoparticles. Angew Chem Int Ed Engl 2016; 55(36): 10691–10696, https://doi.org/10.1002/anie.201604879.
Liang K., Richardson J.J., Cui J., Caruso F., Doonan C.J., Falcaro P. Metal–organic framework coatings as cytoprotective exoskeletons for living cells. Adv Mater 2016; 28(36): 7910–7914, https://doi.org/10.1002/adma.201602335.
Liang K., Richardson J.J., Doonan C.J., Mulet X., Ju Y., Cui J., Caruso F., Falcaro P. An enzyme-coated metal–organic framework shell for synthetically adaptive cell survival. angewandte chemie international edition. Angew Chem Int Ed Engl 2017; 56(29): 8510–8515, https://doi.org/10.1002/anie.201704120.
Li Y., Zhang K., Liu P., Chen M., Zhong Y., Ye Q., Wei M.Q., Zhao H., Tang Z. Encapsulation of plasmid DNA by nanoscale metal–organic frameworks for efficient gene transportation and expression. Adv Mater 2019; 31(29): e1901570, https://doi.org/10.1002/adma.201901570.
Polash S.A., Garlick-Trease K., Pyreddy S., Periasamy S., Bryant G., Shukla R. Amino acid-coated zeolitic imidazolate framework for delivery of genetic material in prostate cancer cell. Molecules 2023; 28(12): 4875, https://doi.org/10.3390/molecules28124875.
Alyami M.Z., Alsaiari S.K., Li Y., Qutub S.S., Aleisa F.A., Sougrat R., Merzaban J.S., Khashab N.M. Cell-type-specific CRISPR/Cas9 delivery by biomimetic metal organic frameworks. J Am Chem Soc 2020; 142(4): 1715–1720, https://doi.org/10.1021/jacs.9b11638.
Alsaiari S.K., Patil S., Alyami M., Alamoudi K.O., Aleisa F.A., Merzaban J.S., Li M., Khashab N.M. Endosomal escape and delivery of CRISPR/Cas9 genome editing machinery enabled by nanoscale zeolitic imidazolate framework. J Am Chem Soc 2018; 140(1): 143–146, https://doi:10.1021/jacs.7b11754.
Liu C., Xu X., Koivisto O., Zhou W., Jacquemet G., Rosenholm J.M., Zhang H. Improving the knock-in efficiency of the MOF-encapsulated CRISPR/Cas9 system through controllable embedding structures. Nanoscale 2021; 13(39): 16525–16532, https://doi.org/10.1039/d1nr02872c.
Poddar A., Pyreddy S., Carraro F., Dhakal S., Rassell A., Field M.R., Reddy T.S., Falcaro P., Doherty C.M., Shukla R. ZIF-C for targeted RNA interference and CRISPR/Cas9 based gene editing in prostate cancer. Chem Commun (Camb) 2020; 56(98): 15406–15409, https://doi.org/10.1039/d0cc06241c.
Lu G., Li S., Guo Z., Farha O.K., Hauser B.G., Qi X., Wang Y., Wang X., Han S., Liu X., DuChene J.S., Zhang H., Zhang Q., Chen X., Ma J., Loo S.C., Wei W.D., Yang Y., Hupp J.T., Huo F. Imparting functionality to a metal–organic framework material by controlled nanoparticle encapsulation. Nat Chem 2012; 4(4): 310–316, https://doi.org/10.1038/nchem.1272.
Venna S.R., Jasinski J.B., Carreon M.A. Structural evolution of zeolitic imidazolate framework-8. J Am Chem Soc 2010; 132(51): 18030–18033, https://doi.org/10.1021/ja109268m.
Bi J., Lu Y., Dong Y., Gao P. Synthesis of folic acid-modified DOX@ZIF-8 nanoparticles for targeted therapy of liver cancer. J Nanomater 2018; 2018: 1357812, https://doi.org/10.1155/2018/1357812.
Yan J., Liu C., Wu Q., Zhou J., Xu X., Zhang L., Wang D., Yang F., Zhang H. Mineralization of pH-sensitive doxorubicin prodrug in ZIF-8 to enable targeted delivery to solid tumors. Anal Chem 2020; 92(16): 11453–11461, https://doi.org/10.1021/acs.analchem.0c02599.
Zeyni V., Karimi S., Namazi H. Surface PEGylation of ZIF-8 metal-organic framework based on magnetic hydroxyapatite as a pH/magnetic targeting responsive system for anticancer drug delivery. Microporous Mesoporous Mater 2023; 354: 112544, https://doi.org/10.1016/j.micromeso.2023.112544.
Reshmi R., Jiju K.R., Suma S., Nair A.S. Folic acid grafted aminated zeolitic imidazolate framework (ZIF-8) as pH responsive drug carrier for targeted delivery of curcumin. J Drug Deliv Sci Technol 2023; 79: 104098, https://doi.org/10.1016/j.jddst.2022.104098.
Fang J., Yang Y., Xiao W., Zheng B., Lv Y.B., Liu X.L., Ding J. Extremely low frequency alternating magnetic field-triggered and MRI-traced drug delivery by optimized magnetic zeolitic imidazolate framework-90 nanoparticles. Nanoscale 2016; 8(6): 3259–3263, https://doi.org/10.1039/c5nr08086j.
Shi Z., Chen X., Zhang L., Ding S., Wang X., Lei Q., Fang W. FA-PEG decorated MOF nanoparticles as a targeted drug delivery system for controlled release of an autophagy inhibitor. Biomater Sci 2018; 6(10): 2582–2590, https://doi.org/10.1039/c8bm00625c.
Wang Y., Shahi P.K., Xie R., Zhang H., Abdeen A.A., Yodsanit N., Ma Z., Saha K., Pattnaik B.R., Gong S. A pH-responsive silica–metal–organic framework hybrid nanoparticle for the delivery of hydrophilic drugs, nucleic acids, and CRISPR-Cas9 genome-editing machineries. J Control Release 2020; 324: 194–203, https://doi.org/10.1016/j.jconrel.2020.04.052.
Wang S., Ouyang L., Deng G., Deng Z., Wang S. DNA adsorption on nanoscale zeolitic imidazolate framework-8 enabling rational design of a DNA-based nanoprobe for gene detection and regulation in living cells. RSC Adv 2020; 10(51): 31012–31021, https://doi.org/10.1039/d0ra06218a.
Zhang H., James J., Zhao M., Yao Y., Zhang Y., Zhang B., Lin Y.S. Improving hydrostability of ZIF-8 membranes via surface ligand exchange. J Membr Sci 2017; 532: 1–8, https://doi.org/10.1016/j.memsci.2017.01.065.
Kida K., Okita M., Fujita K., Tanaka S., Miyake Y. Formation of high crystalline ZIF-8 in an aqueous solution. CrystEngComm 2013; 15(9): 1794–1801, https://doi.org/10.1039/c2ce26847g.
Zhao H., Li T., Yao C., Gu Z., Liu C., Li J., Yang D. Dual roles of metal–organic frameworks as nanocarriers for miRNA delivery and adjuvants for chemodynamic therapy. ACS Appl Mater Interfaces 2021; 13(5): 6034–6042, https://doi.org/10.1021/acsami.0c21006.
Huang C., Tan W., Zheng J., Zhu C., Huo J, Yang R. Azoreductase-responsive metal–organic framework-based nanodrug for enhanced cancer therapy via breaking hypoxia-induced chemoresistance. ACS Appl Mater Interfaces 2019; 11(29): 25740–25749, https://doi.org/10.1021/acsami.9b08115.
Sorrell T.N., Borovik A.S. Synthesis, structure, and spectroscopic properties of an unusual copper(I) dimer having imidazole ligands. A model for the carbonyl derivative of hemocyanin and implications for the structure of deoxyhemocyanin. J Am Chem Soc 1987; 109(14): 4255–4260, https://doi.org/10.1021/ja00248a020.
Yang X., Tang Q., Jiang Y., Zhang M., Wang M., Mao L. Nanoscale ATP-responsive zeolitic imidazole framework-90 as a general platform for cytosolic protein delivery and genome editing. J Am Chem Soc 2019; 141(9): 3782–3786, https://doi.org/10.1021/jacs.8b11996.
Mokri N., Sepehri Z., Faninam F., Khaleghi S., Kazemi N.M., Hashemi M. Chitosan-coated Zn-metal-organic framework nanocomposites for effective targeted delivery of LNA-antisense miR-224 to colon tumor: in vitro studies. Gene Ther 2022; 29(12): 680–690, https://doi.org/10.1038/s41434-021-00265-7.
Rabiee N., Bagherzadeh M., Jouyandeh M., Zarrintaj P., Saeb M.R., Mozafari M., Shokouhimehr M., Varma R.S. Natural polymers decorated MOF-MXene nanocarriers for co-delivery of doxorubicin/pCRISPR. ACS Appl Bio Mater 2021; 4(6): 5106–5121, https://doi.org/10.1021/acsabm.1c00332.
Zheng Q., Li W., Mao L., Wang M. Nanoscale metal–organic frameworks for the intracellular delivery of CRISPR/Cas9 genome editing machinery. Biomater Sci 2021; 9(21): 7024–7033, https://doi.org/10.1039/d1bm00790d.
Chen Q., Xu M., Zheng W., Xu T., Deng H., Liu J. Se/Ru-decorated porous metal–organic framework nanoparticles for the delivery of pooled siRNAs to reversing multidrug resistance in taxol-resistant breast cancer cells. ACS Appl Mater Interfaces 2017; 9(8): 6712–6724, https://doi.org/10.1021/acsami.6b12792.

Shaykhutdinov I.H., Iliasov P.V., Limareva L.V., Sustretov A.S., Kokorev D.A., Sokolov A.V. Biomineralization of Human Genomic DNA into ZIF-8, a Zeolite-Like Metal-Organic Framework. Sovremennye tehnologii v medicine 2024; 16(1): 5, https://doi.org/10.17691/stm2024.16.1.01