Article Link
Collect
Submit Manuscript
Show Outline
Outline
Graphical Abstract
Abstract
Keywords
Electronic Supplementary Material
References
Show full outline
Hide outline
Research Article

Acid-degradable gadolinium-based nanoscale coordination polymer: A potential platform for targeted drug delivery and potential magnetic resonance imaging

Zhimei He1,§Penghui Zhang1,2,§Yan Xiao1Jingjing Li3Fang Yang4Yang Liu4Jian-Rong Zhang1()Jun-Jie Zhu1()
State Key Laboratory of Analytical Chemistry for Life ScienceSchool of Chemistry and Chemical EngineeringNanjing UniversityNanjing210023China
The Key Laboratory of Biomedical Information Engineering of the Ministry of EducationSchool of Life Science and TechnologyBioinspired Engineering and Biomechanics Center (BEBC)Xi'an Jiaotong UniversityXi'an710049China
School of Medical ImagingXuzhou Medical UniversityXuzhou221006China
State Key Laboratory of BioelectronicsJiangsu Key Laboratory for Biomaterials and DevicesSchool of Biological Sciences and Medical EngineeringSoutheast UniversityNanjing210009China

§Zhimei He and Penghui Zhang contributed equally to this work.

Show Author Information

Graphical Abstract

View original image Download original image

Abstract

During conventional chemotherapy for cancer, nonspecific drug distribution, which causes serious side effects in normal tissues, is a serious limitation. Thus, it is desirable to develop a tumor or intracellular microenvironment-responsive nanosystem for targeted and on-demand drug release. In the present study, we engineered an intelligent pH-activatable nanosystem, in which a gadolinium-doxorubicin-loaded nanoscale coordination polymer (Gd-Dox NCPs) was the core and hyaluronic acid was the targeting shell. Taking advantage of CD44 receptor-mediated recognition, the nanoparticles were internalized selectively into human cervical carcinoma (HeLa) cells, and trapped within acidic compartments where the fluorescence of Dox recovered, along with the acid dismantling of the Gd NCPs, allowing real-time monitoring of drug release. In vitro experiments also showed that the Gd NCPs present enhanced T1 signals after acid-triggered degradation, suggesting their potential use as contrast agents for magnetic resonance imaging. Such nanocarriers, which feature high biodegradation, selective targeting ability, and rapid response to stimulus, demonstrated enhanced therapeutic efficacy in targeted cancer cells and "turned on" T1 signals in vitro, showing great promise for diagnosis and treatment.

Electronic Supplementary Material

Download File(s)
nr-11-2-929_ESM.pdf (2.5 MB)

References

1

Chen, H. C.; Tian, J. W.; He, W. J.; Guo, Z. J. H2O2- activatable and O2-evolving nanoparticles for highly efficient and selective photodynamic therapy against hypoxic tumor cells. J. Am. Chem. Soc. 2015, 137, 1539–1547.

2

Zhang, J.; Yuan, Z. -F.; Wang, Y.; Chen, W. -H.; Luo, G. -F.; Cheng, S. -X.; Zhuo, R. -X.; Zhang, X. -Z. Multifunctional envelope-type mesoporous silica nanoparticles for tumor- triggered targeting drug delivery. J. Am. Chem. Soc. 2013, 135, 5068–5073.

3

Ge, Z. S.; Liu, S. Y. Functional block copolymer assemblies responsive to tumor and intracellular microenvironments for site-specific drug delivery and enhanced imaging performance. Chem. Soc. Rev. 2013, 42, 7289–7325.

4

He, Z. -M.; Zhang, P. -H.; Li, X.; Zhang, J. -R.; Zhu, J. -J. A targeted DNAzyme-nanocomposite probe equipped with built-in Zn2+ arsenal for combined treatment of gene regulation and drug delivery. Sci. Rep. 2016, 6, 22737.

5

Zhang, Z. -Y.; Xu, Y. -D.; Ma, Y. -Y.; Qiu, L. -L.; Wang, Y.; Kong, J. -L.; Xiong, H. -M. Biodegradable ZnO@polymer core–shell nanocarriers: pH-triggered release of doxorubicin in vitro. Angew. Chem., Int. Ed. 2013, 52, 4127–4131.

6

Moore, T. L.; Wang, F. L.; Chen, H. Y.; Grimes, S. W.; Anker, J. N.; Alexis, F. Polymer-coated radioluminescent nanoparticles for quantitative imaging of drug delivery. Adv. Funct. Mater. 2014, 24, 5815–5823.

7

Cheng, K.; Yang, M.; Zhang, R. P.; Qin, C. X.; Su, X. H.; Cheng, Z. Hybrid nanotrimers for dual T1 and T2-weighted magnetic resonance imaging. ACS Nano 2014, 8, 9884–9896.

8

Chakravarty, R.; Valdovinos, H. F.; Chen, F.; Lewis, C. M.; Ellison, P. A.; Luo, H. M.; Meyerand, M. E.; Nickles, R. J.; Cai, W. B. Intrinsically germanium-69-labeled iron oxide nanoparticles: Synthesis and in-vivo dual-modality PET/MR imaging. Adv. Mater. 2014, 26, 5119–5123.

9

Mertens, M. E.; Hermann, A.; Bühren, A.; Olde-Damink, L.; Möckel, D.; Gremse, F.; Ehling, J.; Kiessling, F.; Lammers, T. Iron oxide-labeled collagen scaffolds for non-invasive MR imaging in tissue engineering. Adv. Funct. Mater. 2014, 24, 754–762.

10

Wu, M. Y.; Meng, Q. S.; Chen, Y.; Xu, P. F.; Zhang, S. J.; Li, Y. P.; Zhang, L. X. X.; Wang, M.; Yao, H. L.; Shi, J. L. Ultrasmall confined iron oxide nanoparticle MSNs as a pH-responsive theranostic platform. Adv. Funct. Mater. 2014, 24, 4273–4283.

11

Ding, X.; Liu, J. H.; Li, J. Q.; Wang, F.; Wang, Y. H.; Song, S. Y.; Zhang, H. J. Polydopamine coated manganese oxide nanoparticles with ultrahigh relaxivity as nanotheranostic agents for magnetic resonance imaging guided synergetic chemo-/photothermal therapy. Chem. Sci. 2016, 7, 6695–6700.

12

Viger, M. L.; Sankaranarayanan, J.; de Gracia Lux, C.; Chan, M. N.; Almutairi, A. Collective activation of MRI agents via encapsulation and disease-triggered release. J. Am. Chem. Soc. 2013, 135, 7847–7850.

13

Zhang, S. R.; Malloy, C. R.; Sherry, A. D. MRI thermometry based on PARACEST agents. J. Am. Chem. Soc. 2005, 127, 17572–17573.

14

Tu, C. Q.; Nagao, R.; Louie, A. Y. Multimodal magnetic- resonance/optical-imaging contrast agent sensitive to NADH. Angew. Chem., Int. Ed. 2009, 48, 6547–6551.

15

Zhang, S. R.; Wu, K. C.; Sherry, A. D. A novel pH-sensitive MRI contrast agent. Angew. Chem., Int. Ed. 1999, 38, 3192–3194.

16

Strauch, R. C.; Mastarone, D. J.; Sukerkar, P. A.; Song, Y.; Ipsaro, J. J.; Meade, T. J. Reporter protein-targeted probes for magnetic resonance imaging. J. Am. Chem. Soc. 2011, 133, 16346–16349.

17

Kim, T.; Cho, E. -J.; Chae, Y.; Kim, M.; Oh, A.; Jin, J. H.; Lee, E. -S.; Baik, H.; Haam, S.; Suh, J. -S. et al. Urchin-shaped manganese oxide nanoparticles as pH-responsive activatable T1 contrast agents for magnetic resonance imaging. Angew. Chem., Int. Ed. 2011, 50, 10589–10593.

18

Fan, H. H.; Zhao, Z. L.; Yan, G. B.; Zhang, X. B.; Yang, C.; Meng, H. M.; Chen, Z.; Liu, H.; Tan, W. H. A smart DNAzyme–MnO2 nanosystem for efficient gene silencing. Angew. Chem., Int. Ed. 2015, 54, 4801–4805.

19

Yu, L. D.; Chen, Y.; Wu, M. Y.; Cai, X. J.; Yao, H. L.; Zhang, L. L.; Chen, H. R.; Shi, J. L. "Manganese extraction" strategy enables tumor-sensitive biodegradability and theranostics of nanoparticles. J. Am. Chem. Soc. 2016, 138, 9881–9894.

20

Wang, Z. Z.; Chen, Z. W.; Liu, Z.; Shi, P.; Dong, K.; Ju, E. G.; Ren, J. S.; Qu, X. G. A multi-stimuli responsive gold nanocage-hyaluronic platform for targeted photothermal and chemotherapy. Biomaterials 2014, 35, 9678–9688.

21

Chen, S.; Lei, Q.; Qiu, W. -X.; Liu, L. -H.; Zheng, D. -W.; Fan, J. -X.; Rong, L.; Sun, Y. -X.; Zhang, X. -Z. Mitochondria- targeting "nanoheater" for enhanced photothermal/chemo- therapy. Biomaterials 2017, 117, 92–104.

22

Li, J. C.; Hu, Y.; Yang, J.; Wei, P.; Sun, W. J.; Shen, M. W.; Zhang, G. X.; Shi, X. Y. Hyaluronic acid-modified Fe3O4@Au core/shell nanostars for multimodal imaging and photothermal therapy of tumors. Biomaterials 2015, 38, 10–21.

23

Muhammad, F.; Guo, M. Y.; Guo, Y. J.; Qi, W. X.; Qu, F. Y.; Sun, F. X.; Zhao, H. J.; Zhu, G. S. Acid degradable ZnO quantum dots as a platform for targeted delivery of an anticancer drug. J. Mater. Chem. 2011, 21, 13406–13412.

24

Bouma, J.; Beijnen, J. H.; Bult, A.; Underberg, W. J. M. Anthracycline antitumour agents. Pharm. Weekbl. 1986, 8, 109–133.

25

Ji, H. W.; Dong, K.; Yan, Z. Q.; Ding, C.; Chen, Z. W.; Ren, J. S.; Qu, X. G. Bacterial hyaluronidase self-triggered prodrug release for chemo-photothermal synergistic treatment of bacterial infection. Small 2016, 12, 6200–6206.

26

Zhou, K. J.; Liu, H. M.; Zhang, S. R.; Huang, X. N.; Wang, Y. G.; Huang, G.; Sumer, B. D.; Gao, J. M. Multicolored pH-tunable and activatable fluorescence nanoplatform responsive to physiologic pH stimuli. J. Am. Chem. Soc. 2012, 134, 7803–7811.

27

Ke, C. -J.; Su, T. -Y.; Chen, H. -L.; Liu, H. -L.; Chiang, W. -L.; Chu, P. -C.; Xia, Y. N.; Sung, H. -W. Smart multifunctional hollow microspheres for the quick release of drugs in intracellular lysosomal compartments. Angew. Chem., Int. Ed. 2011, 50, 8086–8089.

28

Miyata, K.; Oba, M.; Nakanishi, M.; Fukushima, S.; Yamasaki, Y.; Koyama, H.; Nishiyama, N.; Kataoka, K. Polyplexes from poly(aspartamide) bearing 1, 2-diaminoethane side chains induce pH-selective, endosomal membrane destabilization with amplified transfection and negligible cytotoxicity. J. Am. Chem. Soc. 2008, 130, 16287–16294.

29

Liu, Y. L.; Ai, K. L.; Lu, L. H. Polydopamine and its derivative materials: Synthesis and promising applications in energy, environmental, and biomedical fields. Chem. Rev. 2014, 114, 5057–5115.

30

Dong, Z. L.; Gong, H.; Gao, M.; Zhu, W. W.; Sun, X. Q.; Feng, L. Z.; Fu, T. T.; Li, Y. G.; Liu, Z. Polydopamine nanoparticles as a versatile molecular loading platform to enable imaging-guided cancer combination therapy. Theranostics 2016, 6, 1031–1042.

31

Qhattal, H. S. S.; Liu, X. L. Characterization of CD44-mediated cancer cell uptake and intracellular distribution of hyaluronan- grafted liposomes. Mol. Pharmaceutics 2011, 8, 1233–1246.

32

Jing, L. J.; Shao, S. M.; Wang, Y.; Yang, Y. B.; Yue, X. L.; Dai, Z. F. Hyaluronic acid modified hollow prussian blue nanoparticles loading 10-hydroxycamptothecin for targeting thermochemotherapy of cancer. Theranostics 2016, 6, 40–53.

33

Sarparast, M.; Noori, A.; Ilkhani, H.; Bathaie, S. Z.; El-Kady, M. F.; Wang, L. J.; Pham, H.; Marsh, K. L.; Kaner, R. B.; Mousavi, M. F. Cadmium nanoclusters in a protein matrix: Synthesis, characterization, and application in targeted drug delivery and cellular imaging. Nano Res. 2016, 9, 3229–3246.

34

Zhao, Q. F.; Geng, H. J.; Wang, Y.; Gao, Y. K.; Huang, J. H.; Wang, Y.; Zhang, J. H.; Wang, S. L. Hyaluronic acid oligosaccharide modified redox-responsive mesoporous silica nanoparticles for targeted drug delivery. ACS Appl. Mater. Interfaces 2014, 6, 20290–20299.

35

Choi, K. Y.; Yoon, H. Y.; Kim, J. -H.; Bae, S. M.; Park, R. -W.; Kang, Y. M.; Kim, I. -S.; Kwon, I. C.; Choi, K.; Jeong, S. Y. et al. Smart nanocarrier based on PEGylated hyaluronic acid for cancer therapy. ACS Nano 2011, 5, 8591–8599.

36

Thomas, A. P.; Babu, P. S. S.; Nair, S. A.; Ramakrishnan, S.; Ramaiah, D.; Chandrashekar, T. K.; Srinivasan, A.; Pillai, M. R. meso-Tetrakis(p-sulfonatophenyl)N-confused porphyrin tetrasodium salt: A potential sensitizer for photodynamic therapy. J. Med. Chem. 2012, 55, 5110–5120.

37

Li, J. J.; You, J.; Dai, Y.; Shi, M. L.; Han, C. P.; Xu, K. Gadolinium oxide nanoparticles and aptamer-functionalized silver nanoclusters-based multimodal molecular imaging nanoprobe for optical/magnetic resonance cancer cell imaging. Anal. Chem. 2014, 86, 11306–11311.

38

Fang, J.; Yang, Y.; Xiao, W.; Zheng, B. W.; 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, 3259–3263.

Nano Research
Pages 929-939
Cite this article:
He Z, Zhang P, Xiao Y, et al. Acid-degradable gadolinium-based nanoscale coordination polymer: A potential platform for targeted drug delivery and potential magnetic resonance imaging. Nano Research, 2018, 11(2): 929-939. https://doi.org/10.1007/s12274-017-1705-1
Metrics & Citations  
Article History
Copyright
Return