Core-shell and co-doped nanoscale metal-organic particles (NMOPs) obtained via post-synthesis cation exchange for multimodal imaging and synergistic thermo-radiotherapy
Source abstract
Abstract
Nanoscale metal-organic particles (NMOPs) have recently shown great promise in the area of nanomedicine owing to their tunable compositions, highly enriched functionalities, well-defined sizes/shapes and intrinsic biodegradability. Herein, we describe the fabrication of NMOPs with both core-shell and co-doped structures via a post-synthesis cation exchange method for applications in multimodal imaging and combined photothermal and radiation therapy of cancer. Template NMOPs containing Mn2+ and IR825, a near-infrared (NIR) dye, are first synthesized and then mixed with Hf4+ to obtain core-shell and co-doped Mn/Hf-IR825 NMOPs depending on the dose of added Hf4+ ions. In these NMOPs, Mn2+ offers strong T1 magnetic resonance (MR) contrast, Hf4+ is a high-Z element with excellent computed tomography signal enhancement ability and radio-sensitization capability, and IR825 exhibits rather high NIR absorbance. After coating with polydopamine (PDA) and further conjugation with polyethylene glycol (PEG), the co-doped Mn/Hf-IR825@PDA-PEG particles (NMOP-PEG) showed efficient tumor-homing ability after intravenous injection, as illustrated by MR and photoacoustic (PA) imaging. Utilizing NMOP-PEG achieved excellent tumor killing efficacy through in vivo photothermal and radiation synergistic therapy in our mouse tumor model experiments. Importantly, our NMOP-PEG showed no appreciable toxicity to the treated mice and could be efficiently excreted. Our work presents a facile method to fabricate NMOP-PEG with multi-component structures as a biodegradable, multifunctional nanoplatform for multimodal image-guided combination cancer therapy. Nanoparticles that offer imaging-guided attacks on cancer cells using both photothermal and radiation therapies are now possible. Zhuang Liu from Soochow University in China and colleagues aimed to solve several issue affecting clinical cancer treatments by tailoring materials known as nanoscale metal-organic frameworks. Through cation exchange, the team added hafnium — a metal that strongly absorbs X-ray radiation — to a manganese–organic dye framework capable of providing magnetic resonance images and directing photothermal energy to tumours. After applying a polymer coating to improve physiological stability, the team injected the nanoparticles in mouse models and activated them with a laser. These experiments revealed the nanomedicine had a high tumour killing efficacy due to its multiple modes of action. Cytotoxicity in the trials was minimal, with all nanoparticles excreted from the mice within one month. Core-shell & co-doping nanoscale metal-organic particles (NMOPs), with high strong NIR absorbance, high radio-sensitizing capability and intrinsic biodegradability are developed via a post-synthesis cation exchange strategy for multimodal imaging guided synergistic thermo-radiotherapy. After coating with polydopamine and further conjugation with polyethylene glycol (PEG), such NMOP-PEG nanoparticles show effective tumor retention, and could be utilized for effective synergistic thermo-radiotherapy of cancer. Importantly, those NMOPs show no appreciable toxicity to the treated mice, and could be rapidly excreted from the body owing to their biodegradability.
Source: openalex_inverted_index · Quality: baseline
Research context
OpenAlex topics: Nanoplatforms for cancer theranostics · Photoacoustic and Ultrasonic Imaging · Extracellular vesicles in disease
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (55)
Show source-provided references
1. Jones, E. L., Prosnitz, L. R., Dewhirst, M. W., Marcom, P. K., Hardenbergh, P. H., Marks, L. B., Brizel, D. M. & Vujaskovic, Z. Thermochemoradiotherapy improves oxygenation in locally advanced breast cancer. Clin. Cancer Res. 10, 4287–4293 (2004).10.1158/1078-0432.CCR-04-0133 ↗
2. Dewar, J. A., Arriagada, R., Benhamou, S., Benhamou, E., Bretel, J. J., Pellae‐Cosset, B., Marin, J. L., Petit, J. Y., Contesso, G. & Sarrazin, D. Local relapse and contralateral tumor rates in patients with breast cancer treated with conservative surgery and radiotherapy (Institut Gustave Roussy 1970–1982). Cancer 76, 2260–2265 (1995).10.1002/1097-0142(19951201)76:11<2260::AID-CNCR2820761113>3.0.CO;2-D ↗
3. Lord, C. J. & Ashworth, A. The DNA damage response and cancer therapy. Nature 481, 287–294 (2012).10.1038/nature10760 ↗
4. Wilson, W. R. & Hay, M. P. Targeting hypoxia in cancer therapy. Nat. Rev. Cancer 11, 393–410 (2011).10.1038/nrc3064 ↗
5. Sun, X., Li, X.-F., Russell, J., Xing, L., Urano, M., Li, G. C., Humm, J. L. & Ling, C. C. Changes in tumor hypoxia induced by mild temperature hyperthermia as assessed by dual-tracer immunohistochemistry. Radiother. Oncol. 88, 269–276 (2008).10.1016/j.radonc.2008.05.015 ↗
6. Huang, W.-C., Chiang, W.-H., Cheng, Y.-H., Lin, W.-C., Yu, C.-F., Yen, C.-Y., Yeh, C.-K., Chern, C.-S., Chiang, C.-S. & Chiu, H.-C. Tumortropic monocyte-mediated delivery of echogenic polymer bubbles and therapeutic vesicles for chemotherapy of tumor hypoxia. Biomaterials 71, 71–83 (2015).10.1016/j.biomaterials.2015.08.033 ↗
7. Hu, J. L., Liu, L. P., Yang, S. L., Fang, X., Wen, L., Ren, Q. G. & Yu, C. Hepatitis B virus induces hypoxia-inducible factor-2α expression through hepatitis B virus X protein. Oncol. Rep. 35, 1443–1448 (2016).10.3892/or.2015.4480 ↗
8. Cheng, L., Shen, S., Shi, S., Yi, Y., Wang, X., Song, G., Yang, K., Liu, G., Barnhart, T. E. & Cai, W. FeSe2‐decorated Bi2Se3 nanosheets fabricated via cation exchange for chelator‐free 64Cu‐labeling and multimodal image‐guided photothermal‐radiation therapy. Adv. Funct. Mater. 26, 2185–2197 (2016).10.1002/adfm.201504810 ↗
9. Joh, D. Y., Sun, L., Stangl, M., Al Zaki, A., Murty, S., Santoiemma, P. P., Davis, J. J., Baumann, B. C., Alonso-Basanta, M. & Bhang, D. Selective targeting of brain tumors with gold nanoparticle-induced radiosensitization. PLoS ONE 8, e62425 (2013).10.1371/journal.pone.0062425 ↗
10. Zhang, X. D., Luo, Z., Chen, J., Shen, X., Song, S., Sun, Y., Fan, S., Fan, F., Leong, D. T. & Xie, J. Ultrasmall Au10−12 (SG) 10−12 nanomolecules for high tumor specificity and cancer radiotherapy. Adv. Mater. 26, 4565–4568 (2014).10.1002/adma.201400866 ↗
11. Xiao, Q., Zheng, X., Bu, W., Ge, W., Zhang, S., Chen, F., Xing, H., Ren, Q., Fan, W. & Zhao, K. A core/satellite multifunctional nanotheranostic for in vivo imaging and tumor eradication by radiation/photothermal synergistic therapy. J. Am. Chem. Soc. 135, 13041–13048 (2013).10.1021/ja404985w ↗
12. Gai, S., Li, C., Yang, P. & Lin, J. Recent progress in rare earth micro/nanocrystals: soft chemical synthesis, luminescent properties, and biomedical applications. Chem. Rev. 114, 2343–2389 (2013).10.1021/cr4001594 ↗
13. Zhang, C., Zhao, K., Bu, W., Ni, D., Liu, Y., Feng, J. & Shi, J. Marriage of scintillator and semiconductor for synchronous radiotherapy and deep photodynamic therapy with diminished oxygen dependence. Angew. Chem. Int. Ed. 127, 1790–1794 (2015).10.1002/ange.201408472 ↗
14. Yong, Y., Cheng, X., Bao, T., Zu, M., Yan, L., Yin, W., Ge, C., Wang, D., Gu, Z. & Zhao, Y. Tungsten sulfide quantum dots as multifunctional nanotheranostics for in vivo dual-modal image-guided photothermal/radiotherapy synergistic therapy. ACS Nano 9, 12451–12463 (2015).10.1021/acsnano.5b05825 ↗
15. Yong, Y., Cheng, X., Bao, T., Zu, M., Yan, L., Yin, W., Ge, C., Wang, D., Gu, Z. & Zhao, Y. Tungsten sulfide quantum dots as multifunctional nanotheranostics for in vivo dual-modal image-guided photothermal/radiotherapy synergistic therapy. ACS Nano 9, 12451–12463 (2015).10.1021/acsnano.5b05825 ↗
16. Li, H., Eddaoudi, M., O’Keeffe, M. & Yaghi, O. M. Design and synthesis of an exceptionally stable and highly porous metal-organic framework. Nature 402, 276–279 (1999).10.1038/46248 ↗
17. Lee, J., Farha, O. K., Roberts, J., Scheidt, K. A., Nguyen, S. T. & Hupp, J. T. Metal–organic framework materials as catalysts. Chem. Soc. Rev. 38, 1450–1459 (2009).10.1039/b807080f ↗
18. Chen, B., Eddaoudi, M., Hyde, S., O’keeffe, M. & Yaghi, O. Interwoven metal-organic framework on a periodic minimal surface with extra-large pores. Science 291, 1021–1023 (2001).10.1126/science.1056598 ↗
19. Chen, B., Ockwig, N. W., Millward, A. R., Contreras, D. S. & Yaghi, O. M. High H2 adsorption in a microporous metal–organic framework with open metal sites. Angew. Chem. Int. Ed. 117, 4823–4827 (2005).10.1002/ange.200462787 ↗
20. Kreno, L. E., Leong, K., Farha, O. K., Allendorf, M., Van Duyne, R. P. & Hupp, J. T. Metal–organic framework materials as chemical sensors. Chem. Rev. 112, 1105–1125 (2011).10.1021/cr200324t ↗
21. Dinca, M., Dailly, A., Liu, Y., Brown, C. M., Neumann, D. A. & Long, J. R. Hydrogen storage in a microporous metal-organic framework with exposed Mn2+ coordination sites. J. Am. Chem. Soc. 128, 16876–16883 (2006).10.1021/ja0656853 ↗
22. Liu, B., Shioyama, H., Akita, T. & Xu, Q. Metal-organic framework as a template for porous carbon synthesis. J. Am. Chem. Soc. 130, 5390–5391 (2008).10.1021/ja7106146 ↗
23. Li, P.-Z., Wang, X.-J., Liu, J., Lim, J. S., Zou, R. & Zhao, Y. A triazole-containing metal–organic framework as a highly effective and substrate size-dependent catalyst for CO2 conversion. J. Am. Chem. Soc. 138, 2142–2145 (2016).10.1021/jacs.5b13335 ↗
24. Lv, Y., Shi, P., Shen, W., Chen, X. & Zhao, G. A series of novel Zn (II) and Mn (II) metal-organic frameworks constructed by 2,4-bis-oxyacetate-benzoic acid: syntheses, structures and photoluminescence. Sci. China. Chem 58, 448–456 (2015).10.1007/s11426-014-5161-4 ↗
25. Zhou, H., Li, M., Li, D., Zhang, J. & Chen, X. Thermal expansion behaviors of Mn (II)-pyridylbenzoate frameworks based on metal-carboxylate chains. Sci. China Chem 57, 365–370 (2014).10.1007/s11426-013-5048-9 ↗
26. Cai, W., Chu, C. C., Liu, G. & Wáng, Y. X. J. Metal–organic framework‐based nanomedicine platforms for drug delivery and molecular imaging. Small 11, 4806–4822 (2015).10.1002/smll.201500802 ↗
27. 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. 5, 4182 (2014).10.1038/ncomms5182 ↗
28. Horcajada, P., Chalati, T., Serre, C., Gillet, B., Sebrie, C., Baati, T., Eubank, J. F., Heurtaux, D., Clayette, P. & Kreuz, C. Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging. Nat. Mater. 9, 172–178 (2010).10.1038/nmat2608 ↗
29. Della Rocca, J., Liu, D. & Lin, W. Nanoscale metal–organic frameworks for biomedical imaging and drug delivery. Acc. Chem. Res. 44, 957–968 (2011).10.1021/ar200028a ↗
30. An, J., Geib, S. J. & Rosi, N. L. Cation-triggered drug release from a porous zinc−adeninate metal−organic framework. J. Am. Chem. Soc. 131, 8376–8377 (2009).10.1021/ja902972w ↗
31. Keskin, S. & Kızılel, S. Biomedical applications of metal organic frameworks. Ind. Eng. Chem. Res. 50, 1799–1812 (2011).10.1021/ie101312k ↗
32. Zhou, H.-C., Long, J. R. & Yaghi, O. M. Introduction to metal–organic frameworks. Chem. Rev. 112, 673–674 (2012).10.1021/cr300014x ↗
33. Horcajada, P., Gref, R., Baati, T., Allan, P. K., Maurin, G., Couvreur, P., Férey, G., Morris, R. E. & Serre, C. Metal–organic frameworks in biomedicine. Chem. Rev. 112, 1232–1268 (2011).10.1021/cr200256v ↗
34. Feng, D., Gu, Z. Y., Li, J. R., Jiang, H. L., Wei, Z. & Zhou, H. C. Zirconium‐metalloporphyrin PCN‐222: mesoporous metal–organic frameworks with ultrahigh stability as biomimetic catalysts. Angew. Chem. Int. Ed. 124, 10453–10456 (2012).10.1002/ange.201204475 ↗
35. Park, J., Jiang, Q., Feng, D., Mao, L. & Zhou, H.-C. Size-controlled synthesis of porphyrinic metal–organic framework and functionalization for targeted photodynamic therapy. J. Am. Chem. Soc. 138, 3518–3525 (2016).10.1021/jacs.6b00007 ↗
36. Diring, S., Wang, D. O., Kim, C., Kondo, M., Chen, Y., Kitagawa, S., Kamei, K.-i. & Furukawa, S. Localized cell stimulation by nitric oxide using a photoactive porous coordination polymer platform. Nat. Commun. 4, 2684 (2013).10.1038/ncomms3684 ↗
37. Yang, Y., Liu, J., Liang, C., Feng, L., Fu, T., Dong, Z., Chao, Y., Li, Y., Lu, G. & Chen, M. Nanoscale metal-organic particles with rapid clearance for MR imaging guided photothermal therapy. ACS Nano 10, 2774–2781 (2016).10.1021/acsnano.5b07882 ↗
38. Cheng, L., He, W., Gong, H., Wang, C., Chen, Q., Cheng, Z. & Liu, Z. PEGylated micelle nanoparticles encapsulating a non‐fluorescent near‐infrared organic dye as a safe and highly‐effective photothermal agent for in vivo cancer therapy. Adv. Funct. Mater. 23, 5893–5902 (2013).10.1002/adfm.201301045 ↗
39. Viswanathan, S., Kovacs, Z., Green, K. N., Ratnakar, S. J. & Sherry, A. D. Alternatives to gadolinium-based metal chelates for magnetic resonance imaging†. Chem. Rev. 110, 2960–3018 (2010).10.1021/cr900284a ↗
40. Taylor, K. M., Rieter, W. J. & Lin, W. Manganese-based nanoscale metal−organic frameworks for magnetic resonance imaging. J. Am. Chem. Soc. 130, 14358–14359 (2008).10.1021/ja803777x ↗
41. Ren, W., Tian, G., Zhou, L., Yin, W., Yan, L., Jin, S., Zu, Y., Li, S., Gu, Z. & Zhao, Y. Lanthanide ion-doped GdPO 4 nanorods with dual-modal bio-optical and magnetic resonance imaging properties. Nanoscale 4, 3754–3760 (2012).10.1039/c2nr30683b ↗
42. Mehravi, B., Ahmadi, M., Amanlou, M., Mostaar, A., Ardestani, M. S. & Ghalandarlaki, N. Conjugation of glucosamine with Gd3+-based nanoporous silica using a heterobifunctional ANB-NOS crosslinker for imaging of cancer cells. Int. J. Nanomed. 8, 3383–3394 (2013).10.2147/IJN.S44829 ↗
43. Boyle, W. S., Burk, L. M., Zhou, O. Z. & Lin, W. Zr-and Hf-based nanoscale metal–organic frameworks as contrast agents for computed tomography. J. Mater. Chem. 22, 18139–18144 (2012).10.1039/c2jm32299d ↗
44. Xia, A., Chen, M., Gao, Y., Wu, D., Feng, W. & Li, F. Gd3+ complex-modified NaLuF 4-based upconversion nanophosphors for trimodality imaging of NIR-to-NIR upconversion luminescence, X-Ray computed tomography and magnetic resonance. Biomaterials 33, 5394–5405 (2012).10.1016/j.biomaterials.2012.04.025 ↗
45. McCrary, J., Plassmann, E. H., Puckett, J., Conner, A. & Zimmermann, G. X-ray attenuation-coefficient measurements. Phy. Rev. 153, 307 (1967).10.1103/PhysRev.153.307 ↗
46. Sidhu, S. & McGuire, J. An X‐ray diffraction study of the hafnium‐hydrogen system. J. Appl. Phys. 23, 1257–1261 (1952).10.1063/1.1702043 ↗
47. Su, X.-Y., Liu, P.-D., Wu, H. & Gu, N. Enhancement of radiosensitization by metal-based nanoparticles in cancer radiation therapy. Cancer Biol. Med. 11, 86–91 (2014).
48. Xu, M. & Wang, L. V. Photoacoustic imaging in biomedicine. Rev. Sci. Instrum. 77, 041101 (2006).10.1063/1.2195024 ↗
49. Cheng, L., Liu, J., Gu, X., Gong, H., Shi, X., Liu, T., Wang, C., Wang, X., Liu, G. & Xing, H. PEGylated WS2 nanosheets as a multifunctional theranostic agent for in vivo dual‐modal CT/photoacoustic imaging guided photothermal therapy. Adv. Mater. 26, 1886–1893 (2014).10.1002/adma.201304497 ↗
50. Zeng, J., Cheng, M., Wang, Y., Wen, L., Chen, L., Li, Z., Wu, Y., Gao, M. & Chai, Z. pH‐responsive Fe(III)–gallic acid nanoparticles for in vivo photoacoustic imaging‐guided photothermal therapy. Adv. Health. Mater. 5, 772–780 (2016).10.1002/adhm.201500898 ↗
51. Sreejith, S., Joseph, J., Lin, M., Menon, N. V., Borah, P., Ng, H. J., Loong, Y. X., Kang, Y., Yu, S. W.-K. & Zhao, Y. Near-infrared squaraine dye encapsulated micelles for in vivo fluorescence and photoacoustic bimodal imaging. ACS Nano 9, 5695–5704 (2015).10.1021/acsnano.5b02172 ↗
52. Song, K., Huang, P., Yi, C., Ning, B., Hu, S., Nie, L., Chen, X. & Nie, Z. Photoacoustic and colorimetric visualization of latent fingerprints. ACS Nano 9, 12344–12348 (2015).10.1021/acsnano.5b05629 ↗
53. Jin, C. S., Lovell, J. F., Chen, J. & Zheng, G. Ablation of hypoxic tumors with dose-equivalent photothermal, but not photodynamic, therapy using a nanostructured porphyrin assembly. ACS Nano 7, 2541–2550 (2013).10.1021/nn3058642 ↗
54. Song, G., Liang, C., Gong, H., Li, M., Zheng, X., Cheng, L., Yang, K., Jiang, X. & Liu, Z. Core–Shell MnSe@ Bi2Se3 fabricated via a cation exchange method as novel nanotheranostics for multimodal imaging and synergistic thermoradiotherapy. Adv. Mater. 27, 6110–6117 (2015).10.1002/adma.201503006 ↗
55. Chen, Q., Wang, C., Zhan, Z., He, W., Cheng, Z., Li, Y. & Liu, Z. Near-infrared dye bound albumin with separated imaging and therapy wavelength channels for imaging-guided photothermal therapy. Biomaterials 35, 8206–8214 (2014).10.1016/j.biomaterials.2014.06.013 ↗