Metal-organic Nanopharmaceuticals

Author(s): Benjamin Steinborn, Ulrich Lächelt*

Journal Name: Pharmaceutical Nanotechnology

Volume 8 , Issue 3 , 2020


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Coordinative interactions between multivalent metal ions and drug derivatives with Lewis base functions give rise to nanoscale coordination polymers (NCPs) as delivery systems. As the pharmacologically active agent constitutes a main building block of the nanomaterial, the resulting drug loadings are typically very high. By additionally selecting metal ions with favorable pharmacological or physicochemical properties, the obtained NCPs are predominantly composed of active components which serve individual purposes, such as pharmacotherapy, photosensitization, multimodal imaging, chemodynamic therapy or radiosensitization. By this approach, the assembly of drug molecules into NCPs modulates pharmacokinetics, combines pharmacological drug action with specific characteristics of metal components and provides a strategy to generate tailorable multifunctional nanoparticles. This article reviews different applications and recent examples of such highly functional nanopharmaceuticals with a high ‘material economy’.

Lay Summary: Nanoparticles, that are small enough to circulate in the bloodstream and can carry cargo molecules, such as drugs, imaging or contrast agents, are attractive materials for pharmaceutical applications. A high loading capacity is a generally aspired parameter of nanopharmaceuticals to minimize patient exposure to unnecessary nanomaterial. Pharmaceutical agents containing Lewis base functions in their molecular structure can directly be assembled into metal-organic nanopharmaceuticals by coordinative interaction with metal ions. Such coordination polymers generally feature extraordinarily high loading capacities and the flexibility to encapsulate different agents for a simultaneous delivery in combination therapy or ‘theranostic’ applications.

Keywords: Cancer therapy, drug delivery, metal-organic frameworks, nanopharmaceuticals, nanoscale coordination polymers, photodynamic therapy, radiotherapy, theranostics.

[1]
Moghadam PZ, Li A, Wiggin SB, et al. Development of a cambridge structural database subset: a collection of metal-organic frameworks for past, present, and future. Chem Mater 2017; 29(7): 2618-25.
[http://dx.doi.org/10.1021/acs.chemmater.7b00441]
[2]
He C, Liu D, Lin W. Nanomedicine applications of hybrid nanomaterials built from metal-ligand coordination bonds: nanoscale metal-organic frameworks and nanoscale coordination polymers. Chem Rev 2015; 115(19): 11079-108.
[http://dx.doi.org/10.1021/acs.chemrev.5b00125] [PMID: 26312730]
[3]
Freund R, Lächelt U, Gruber T, Rühle B, Wuttke S. Multifunctional efficiency: extending the concept of atom economy to functional nanomaterials. ACS Nano 2018; 12(3): 2094-105.
[http://dx.doi.org/10.1021/acsnano.8b00932] [PMID: 29533060]
[4]
Batten SR, Champness NR, Chen X-M, et al. Coordination polymers, metal-organic frameworks and the need for terminology guidelines. CrystEngComm 2012; 14(9): 3001-4.
[http://dx.doi.org/10.1039/c2ce06488j]
[5]
Batten SR, Champness NR, Chen X-M, et al. Terminology of metal-organic frameworks and coordination polymers (IUPAC Recommendations 2013). Pure Appl Chem 2013; 85(8): 1715-24.
[http://dx.doi.org/10.1351/PAC-REC-12-11-20]
[6]
Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer 2012; 12(4): 278-87.
[http://dx.doi.org/10.1038/nrc3236] [PMID: 22437872]
[7]
Baudino TA. Targeted cancer therapy: the next generation of cancer treatment. Curr Drug Discov Technol 2015; 12(1): 3-20.
[http://dx.doi.org/10.2174/1570163812666150602144310] [PMID: 26033233]
[8]
Velcheti V, Schalper K. Basic overview of current immunotherapy approaches in cancer. American Society of Clinical Oncology educational book American Society of Clinical Oncology Annual Meeting. 35 : 298-308 .
[9]
Golombek SK, May J-N, Theek B, et al. Tumor targeting via EPR: strategies to enhance patient responses. Adv Drug Deliv Rev 2018; 130: 17-38.
[http://dx.doi.org/10.1016/j.addr.2018.07.007] [PMID: 30009886]
[10]
Rahman AM, Yusuf SW, Ewer MS. Anthracycline-induced cardiotoxicity and the cardiac-sparing effect of liposomal formulation. Int J Nanomedicine 2007; 2(4): 567-83.
[PMID: 18203425]
[11]
Franco YL, Vaidya TR, Ait-Oudhia S. Anticancer and cardio-protective effects of liposomal doxorubicin in the treatment of breast cancer. Breast Cancer 2018; 10: 131-41.
[http://dx.doi.org/10.2147/BCTT.S170239] [PMID: 30237735]
[12]
Gyongyosi M, Lukovic D, Zlabinger K, et al. Liposomal doxorubicin attenuates cardiotoxicity via induction of interferon-related DNA damage resistance. Cardiovasc Res 2020; 116(5): 970-82.
[http://dx.doi.org/10.1093/cvr/cvz192] [PMID: 31346605]
[13]
Cheung BC, Sun TH, Leenhouts JM, Cullis PR. Loading of doxorubicin into liposomes by forming Mn2+-drug complexes. Biochim Biophys Acta 1998; 1414(1-2): 205-16.
[http://dx.doi.org/10.1016/S0005-2736(98)00168-0] [PMID: 9804955]
[14]
Kheirolomoom A, Ingham ES, Commisso J, Abushaban N, Ferrara KW. Intracellular trafficking of a pH-responsive drug metal complex. J Control Release 2016; 243: 232-42.
[http://dx.doi.org/10.1016/j.jconrel.2016.10.012] [PMID: 27746275]
[15]
Kheirolomoom A, Mahakian LM, Lai CY, et al. Copper-doxorubicin as a nanoparticle cargo retains efficacy with minimal toxicity. Mol Pharm 2010; 7(6): 1948-58.
[http://dx.doi.org/10.1021/mp100245u] [PMID: 20925429]
[16]
Xing L, Zheng H, Che S. A pH-responsive cleavage route based on a metal-organic coordination bond. Chemistry 2011; 17(26): 7271-5.
[http://dx.doi.org/10.1002/chem.201003005] [PMID: 21567490]
[17]
Imaz I, Rubio-Martínez M, García-Fernández L, et al. Coordination polymer particles as potential drug delivery systems. Chem Commun (Camb) 2010; 46(26): 4737-9.
[http://dx.doi.org/10.1039/c003084h] [PMID: 20485835]
[18]
He Z, Zhang P, Xiao Y, Li J, Yang F, Liu Y, et al. Acid-degradable gadolinium-based nanoscale coordination polymer: a potential platform for targeted drug delivery and potential magnetic resonance imaging. Nano Res 2018; 11(2): 929-39.
[http://dx.doi.org/10.1007/s12274-017-1705-1]
[19]
Tang L, Shi J, Wang X, et al. Coordination polymer nanocapsules prepared using metal-organic framework templates for pH-responsive drug delivery. Nanotechnology 2017; 28(27): 275601
[http://dx.doi.org/10.1088/1361-6528/aa7379] [PMID: 28510533]
[20]
Gao PF, Zheng LL, Liang LJ, Yang XX, Li YF, Huang CZ. A new type of pH-responsive coordination polymer sphere as a vehicle for targeted anticancer drug delivery and sustained release. J Mater Chem B Mater Biol Med 2013; 1(25): 3202-8.
[http://dx.doi.org/10.1039/c3tb00026e] [PMID: 32260920]
[21]
Zhao J, Yang Y, Han X, et al. Redox-sensitive nanoscale coordination polymers for drug delivery and cancer theranostics. ACS Appl Mater Interfaces 2017; 9(28): 23555-63.
[http://dx.doi.org/10.1021/acsami.7b07535] [PMID: 28636308]
[22]
Han K, Zhang W-Y, Zhang J, Ma Z-Y, Han H-Y. pH-responsive nanoscale coordination polymer for efficient drug delivery and real-time release monitoring. Adv Healthc Mater 2017; 6(19): 1700470
[http://dx.doi.org/10.1002/adhm.201700470] [PMID: 28714280]
[23]
Lecumberri E, Dupertuis YM, Miralbell R, Pichard C. Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy. Clin Nutr 2013; 32(6): 894-903.
[http://dx.doi.org/10.1016/j.clnu.2013.03.008] [PMID: 23582951]
[24]
Liu J, Yang G, Zhu W, et al. Light-controlled drug release from singlet-oxygen sensitive nanoscale coordination polymers enabling cancer combination therapy. Biomaterials 2017; 146: 40-8.
[http://dx.doi.org/10.1016/j.biomaterials.2017.09.007] [PMID: 28941551]
[25]
Hirsch FR, Scagliotti GV, Mulshine JL, et al. Lung cancer: current therapies and new targeted treatments. Lancet 2017; 389(10066): 299-311.
[http://dx.doi.org/10.1016/S0140-6736(16)30958-8] [PMID: 27574741]
[26]
Cortez AJ, Tudrej P, Kujawa KA, Lisowska KM. Advances in ovarian cancer therapy. Cancer Chemother Pharmacol 2018; 81(1): 17-38.
[http://dx.doi.org/10.1007/s00280-017-3501-8] [PMID: 29249039]
[27]
Kelland L. The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer 2007; 7(8): 573-84.
[http://dx.doi.org/10.1038/nrc2167] [PMID: 17625587]
[28]
Tapia G, Diaz-Padill I. Molecular mechanisms of platinum resistance in ovarian cancer. United Kingdom: InTech 2013; pp. 205-23.
[http://dx.doi.org/10.5772/55562]
[29]
Rieter WJ, Pott KM, Taylor KM, Lin W. Nanoscale coordination polymers for platinum-based anticancer drug delivery. J Am Chem Soc 2008; 130(35): 11584-5.
[http://dx.doi.org/10.1021/ja803383k] [PMID: 18686947]
[30]
Liu D, Poon C, Lu K, He C, Lin W. Self-assembled nanoscale coordination polymers with trigger release properties for effective anticancer therapy. Nat Commun 2014; 5: 4182.
[http://dx.doi.org/10.1038/ncomms5182] [PMID: 24964370]
[31]
Poon C, He C, Liu D, Lu K, Lin W. Self-assembled nanoscale coordination polymers carrying oxaliplatin and gemcitabine for synergistic combination therapy of pancreatic cancer. J Control Release 2015; 201: 90-9.
[http://dx.doi.org/10.1016/j.jconrel.2015.01.026] [PMID: 25620067]
[32]
He C, Poon C, Chan C, Yamada SD, Lin W. Nanoscale coordination polymers codeliver chemotherapeutics and siRNAs to eradicate tumors of cisplatin-resistant ovarian cancer. J Am Chem Soc 2016; 138(18): 6010-9.
[http://dx.doi.org/10.1021/jacs.6b02486] [PMID: 27088560]
[33]
Liu J, Chen Q, Zhu W, et al. Nanoscale-coordination-polymer-shelled manganese dioxide composite nanoparticles: a multistage redox/pH/H2O2-responsive cancer theranostic nanoplatform. Adv Funct Mater 2017; 27(10): 1605926
[http://dx.doi.org/10.1002/adfm.201605926]
[34]
Adarsh NN, Frias C, Ponnoth Lohidakshan TM, et al. Pt(IV)-based nanoscale coordination polymers: antitumor activity, cellular uptake and interactions with nuclear DNA. Chem Eng J 2018; 340: 94-102.
[http://dx.doi.org/10.1016/j.cej.2018.01.058]
[35]
Yang Y, Xu L, Zhu W, et al. One-pot synthesis of pH-responsive charge-switchable PEGylated nanoscale coordination polymers for improved cancer therapy. Biomaterials 2018; 156: 121-33.
[http://dx.doi.org/10.1016/j.biomaterials.2017.11.038] [PMID: 29195181]
[36]
Hu Y, Lv T, Ma Y, et al. Nanoscale coordination polymers for synergistic NO and chemodynamic therapy of liver cancer. Nano Lett 2019; 19(4): 2731-8.
[http://dx.doi.org/10.1021/acs.nanolett.9b01093] [PMID: 30919635]
[37]
Huxford RC, Dekrafft KE, Boyle WS, Liu D, Lin W. Lipid-coated nanoscale coordination polymers for targeted delivery of antifolates to cancer cells. Chem Sci (Camb) 2012; 3(1): 198-204.
[http://dx.doi.org/10.1039/C1SC00499A] [PMID: 24288587]
[38]
Steinborn B, Hirschle P, Höhn M, et al. Core-shell functionalized zirconium‐pemetrexed coordination nanoparticles as carriers with a high drug content. Adv Ther 2019; 2(11): 1900120
[http://dx.doi.org/10.1002/adtp.201900120]
[39]
Liu D, He C, Poon C, Lin W. Theranostic nanoscale coordination polymers for magnetic resonance imaging and bisphosphonate delivery. J Mater Chem B Mater Biol Med 2014; 2(46): 8249-55.
[http://dx.doi.org/10.1039/C4TB00751D] [PMID: 32262098]
[40]
Thomsen HS. Nephrogenic systemic fibrosis: history and epidemiology. Radiol Clin North Am 2009; 47(5): 827-31. vi.
[http://dx.doi.org/10.1016/j.rcl.2009.05.003] [PMID: 19744597]
[41]
Pan D, Schmieder AH, Wickline SA, Lanza GM. Manganese-based MRI contrast agents: past, present and future. Tetrahedron 2011; 67(44): 8431-44.
[http://dx.doi.org/10.1016/j.tet.2011.07.076] [PMID: 22043109]
[42]
Daniell MD, Hill JS. A history of photodynamic therapy. Aust N Z J Surg 1991; 61(5): 340-8.
[http://dx.doi.org/10.1111/j.1445-2197.1991.tb00230.x] [PMID: 2025186]
[43]
Drugs@FDA: FDA-Approved Drugs. U.S. food and drug administration. Available from: https://www. accessdata.fda.gov/scripts/cder/daf/index.cfmevent=overview.process&ApplNo=020451.
[44]
Lismont M, Dreesen L, Wuttke S. Metal-organic framework nanoparticles in photodynamic therapy: current status and perspectives. Adv Funct Mater 2017; 27(14): 1606314
[http://dx.doi.org/10.1002/adfm.201606314]
[45]
Lu K, He C, Lin W. Nanoscale metal-organic framework for highly effective photodynamic therapy of resistant head and neck cancer. J Am Chem Soc 2014; 136(48): 16712-5.
[http://dx.doi.org/10.1021/ja508679h] [PMID: 25407895]
[46]
Lu K, He C, Lin W. A chlorin-based nanoscale metal-organic framework for photodynamic therapy of colon cancers. J Am Chem Soc 2015; 137(24): 7600-3.
[http://dx.doi.org/10.1021/jacs.5b04069] [PMID: 26068094]
[47]
Yang Y, Zhu W, Feng L, et al. G-quadruplex-based nanoscale coordination polymers to modulate tumor hypoxia and achieve nuclear-targeted drug delivery for enhanced photodynamic therapy. Nano Lett 2018; 18(11): 6867-75.
[http://dx.doi.org/10.1021/acs.nanolett.8b02732] [PMID: 30303384]
[48]
Liu J, Yang Y, Zhu W, et al. Nanoscale metal-organic frameworks for combined photodynamic & radiation therapy in cancer treatment. Biomaterials 2016; 97: 1-9.
[http://dx.doi.org/10.1016/j.biomaterials.2016.04.034] [PMID: 27155362]
[49]
Prencipe G, Tabakman SM, Welsher K, et al. PEG branched polymer for functionalization of nanomaterials with ultralong blood circulation. J Am Chem Soc 2009; 131(13): 4783-7.
[http://dx.doi.org/10.1021/ja809086q] [PMID: 19173646]
[50]
He C, Liu D, Lin W. Self-assembled core-shell nanoparticles for combined chemotherapy and photodynamic therapy of resistant head and neck cancers. ACS Nano 2015; 9(1): 991-1003.
[http://dx.doi.org/10.1021/nn506963h] [PMID: 25559017]
[51]
de-Krafft KE, Xie Z, Cao G, et al. Iodinated nanoscale coordination polymers as potential contrast agents for computed tomography. Angew Chem Int Ed Engl 2009; 48(52): 9901-4.
[http://dx.doi.org/10.1002/anie.200904958] [PMID: 19937883]
[52]
Heismann BJ, Leppert J, Stierstorfer K. Density and atomic number measurements with spectral x-ray attenuation method. J Appl Phys 2003; 94(3): 2073-9.
[http://dx.doi.org/10.1063/1.1586963]
[53]
Lusic H, Grinstaff MW. X-ray-computed tomography contrast agents. Chem Rev 2013; 113(3): 1641-66.
[http://dx.doi.org/10.1021/cr200358s] [PMID: 23210836]
[54]
Solórzano R, Tort O, García-Pardo J, et al. Versatile iron-catechol-based nanoscale coordination polymers with antiretroviral ligand functionalization and their use as efficient carriers in HIV/AIDS therapy. Biomater Sci 2018; 7(1): 178-86.
[http://dx.doi.org/10.1039/C8BM01221K] [PMID: 30507990]
[55]
Chao Y, Liang C, Yang Y, et al. Highly effective radioisotope cancer therapy with a non-therapeutic isotope delivered and sensitized by nanoscale coordination polymers. ACS Nano 2018; 12(8): 7519-28.
[http://dx.doi.org/10.1021/acsnano.8b02400] [PMID: 30047272]
[56]
Song G, Cheng L, Chao Y, Yang K, Liu Z. Emerging nanotechnology and advanced materials for cancer radiation therapy. Adv Mater 2017; 29(32)
[http://dx.doi.org/10.1002/adma.201700996] [PMID: 28643452]
[57]
Heck JG, Feldmann C. Zirconyl acetaminophen phosphate: a nanoscaled analgetic with very high drug load. J Colloid Interface Sci 2016; 481: 69-74.
[http://dx.doi.org/10.1016/j.jcis.2016.07.030] [PMID: 27451036]
[58]
Wang K, Ma X, Shao D, Geng Z, Zhang Z, Wang Z. Coordination-induced assembly of coordination polymer submicrospheres: promising antibacterial and in vitro anticancer activities. Cryst Growth Des 2012; 12(7): 3786-91.
[http://dx.doi.org/10.1021/cg3006162]
[59]
Yang Y, Chao Y, Liu J, Dong Z, He W, Zhang R, et al. Core-shell and co-doped nanoscale metal-organic particles (NMOPs) obtained via post-synthesis cation exchange for multimodal imaging and synergistic thermo-radiotherapy. NPG Asia Mater 2017; 9(1): e344
[60]
Jin Q, Zhu W, Jiang D, et al. Ultra-small iron-gallic acid coordination polymer nanoparticles for chelator-free labeling of 64Cu and multimodal imaging-guided photothermal therapy. Nanoscale 2017; 9(34): 12609-17.
[http://dx.doi.org/10.1039/C7NR03086J] [PMID: 28825066]
[61]
Steinberg I, Huland DM, Vermesh O, Frostig HE, Tummers WS, Gambhir SS. Photoacoustic clinical imaging. Photoacoustics 2019; 14: 77-98.
[http://dx.doi.org/10.1016/j.pacs.2019.05.001] [PMID: 31293884]
[62]
Amorin-Ferre L, Novio F, Simmchen J, Vazquez Mera N, Ruiz-Molina D. Coordination polymer nanoparticles in medicine 2013; 257(19-20): 2839-47.


open access plus

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 8
ISSUE: 3
Year: 2020
Published on: 30 September, 2020
Page: [163 - 190]
Pages: 28
DOI: 10.2174/2211738508666200421113215

Article Metrics

PDF: 23
HTML: 2