Issue

Vol. 11 (2019)

Photostable and Biocompatible Fluorescent Silicon Nanoparticles for Imaging-Guided Co-Delivery of siRNA and Doxorubicin to Drug-Resistant Cancer Cells

https://doi.org/10.1007/s40820-019-0257-1
Daoxia Guo
Laboratory of Nanoscale Biochemical Analysis, Jiangsu Key Laboratory for Carbon‑Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, Jiangsu, People’s Republic of China
Xiaoyuan Ji
Laboratory of Nanoscale Biochemical Analysis, Jiangsu Key Laboratory for Carbon‑Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, Jiangsu, People’s Republic of China
Fei Peng
Laboratory of Nanoscale Biochemical Analysis, Jiangsu Key Laboratory for Carbon‑Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, Jiangsu, People’s Republic of China
Yiling Zhang
Laboratory of Nanoscale Biochemical Analysis, Jiangsu Key Laboratory for Carbon‑Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, Jiangsu, People’s Republic of China
Binbin Chu
Laboratory of Nanoscale Biochemical Analysis, Jiangsu Key Laboratory for Carbon‑Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, Jiangsu, People’s Republic of China
Yuanyuan Su
Laboratory of Nanoscale Biochemical Analysis, Jiangsu Key Laboratory for Carbon‑Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, Jiangsu, People’s Republic of China
Yao He
Laboratory of Nanoscale Biochemical Analysis, Jiangsu Key Laboratory for Carbon‑Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, Jiangsu, People’s Republic of China

Corresponding Author: Yao He

yaohe@suda.edu.cn

Nano-Micro Letters, Vol. 11 (2019), Article Number: 27

Abstract

The development of effective and safe vehicles to deliver small interfering RNA (siRNA) and chemotherapeutics remains a major challenge in RNA interference-based combination therapy with chemotherapeutics, which has emerged as a powerful platform to treat drug-resistant cancer cells. Herein, we describe the development of novel all-in-one fluorescent silicon nanoparticles (SiNPs)-based nanomedicine platform for imaging-guided co-delivery of siRNA and doxorubicin (DOX). This approach enhanced therapeutic efficacy in multidrug-resistant breast cancer cells (i.e., MCF-7/ADR cells). Typically, the SiNP-based nanocarriers enhanced the stability of siRNA in a biological environment (i.e., medium or RNase A) and imparted the responsive release behavior of siRNA, resulting in approximately 80% down-regulation of P-glycoprotein expression. Co-delivery of P-glycoprotein siRNA and DOX led to > 35-fold decrease in the half maximal inhibitory concentration of DOX in comparison with free DOX, indicating the pronounced therapeutic efficiency of the resultant nanocomposites for drug-resistant breast cancer cells. The intracellular time-dependent release behaviors of siRNA and DOX were revealed through tracking the strong and stable fluorescence of SiNPs. These data provide valuable information for designing effective RNA interference-based co-delivery carriers.


Highlights:


1 A novel all-in-one fluorescent nanomedicine platform based on silicon nanoparticles (SiNPs) was developed for imaging-guided co-delivery of short interfering RNA (siRNA) and doxorubicin (DOX).
2 The intracellular time-dependent release behaviors of siRNA and DOX were visually monitored by tracking the strong and stable fluorescence of SiNPs.
3 The SiNPs-based nanocarriers displayed pronounced therapeutic efficiency on drug-resistant breast cancer cells.

Keywords

Fluorescent silicon nanoparticles Drug resistance Gene therapy Bioimaging
Guo, Daoxia, Xiaoyuan Ji, Fei Peng, Yiling Zhang, Binbin Chu, Yuanyuan Su, and Yao He. 2019. “Photostable and Biocompatible Fluorescent Silicon Nanoparticles for Imaging-Guided Co-Delivery of SiRNA and Doxorubicin to Drug-Resistant Cancer Cells”. Nano-Micro Letters 11 (March):27. https://doi.org/10.1007/s40820-019-0257-1.
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. C. Holohan, S. Van Schaeybroeck, D.B. Longley, P.G. Johnston, Cancer drug resistance: an evolving paradigm. Nat. Rev. Cancer 13, 714–726 (2013). https://doi.org/10.1038/nrc3599
  2. M. Abbasi, A. Lavasanifar, H. Uludaˇ, Recent attempts at RNAi-mediated P-glycoprotein downregulation for reversal of multidrug resistance in cancer. Med. Res. Rev. 33, 33–53 (2013). https://doi.org/10.1002/med.20244
  3. P.A. Watson, V.K. Arora, C.L. Sawyers, Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer. Nat. Rev. Cancer 15, 701–711 (2015). https://doi.org/10.1038/nrc4016
  4. A. Fire, S. Xu, M.K. Montgomery, S.A. Kostas, S.E. Driver, C.C. Mello, Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806–811 (1998). https://doi.org/10.1038/35888
  5. S.M. Elbashir, J. Harborth, W. Lendeckel, A. Yalcin, K. Weber, T. Tuschl, Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494–498 (2001). https://doi.org/10.1038/35078107
  6. J.E. Zuckerman, M.E. Davis, Clinical experiences with systemically administered siRNA-based therapeutics in cancer. Nat. Rev. Drug Discov. 14, 843–856 (2015). https://doi.org/10.1038/nrd4685
  7. Y. Min, J.M. Caster, M.J. Eblan, A.Z. Wang, Clinical translation of nanomedicine. Chem. Rev. 115(19), 11147–11190 (2015). https://doi.org/10.1021/acs.chemrev.5b00116
  8. B. Jang, H. Kwon, P. Katila, S.J. Lee, H. Lee, Dual delivery of biological therapeutics for multimodal and synergistic cancer therapies. Adv. Drug Deliv. Rev. 98, 113–133 (2016). https://doi.org/10.1016/j.addr.2015.10.023
  9. X.G. Ding, F. Peng, J. Zhou, W.B. Gong, G. Slaven, K.P. Loh, C.T. Lim, D.T. Leong, Defect engineered bioactive transition metals dichalcogenides quantum dots. Nat. Commun. 10, 41 (2019). https://doi.org/10.1038/s41467-018-07835-1
  10. R. Kanasty, J.R. Dorkin, A. Vegas, D. Anderson, Delivery materials for siRNA therapeutics. Nat. Mater. 12, 967–977 (2013). https://doi.org/10.1038/nmat3765
  11. X. Xu, K. Xie, X.-Q. Zhang, E.M. Pridgen, G.Y. Park et al., Enhancing tumor cell response to chemotherapy through nanoparticle-mediated codelivery of siRNA and cisplatin prodrug. Proc. Natl. Acad. Sci. U.S.A. 110(46), 18638–18643 (2013). https://doi.org/10.1073/pnas.1303958110
  12. A.K. Iyer, A. Singh, S. Ganta, M.M. Amiji, Role of integrated cancer nanomedicine in overcoming drug resistance. Adv. Drug Deliv. Rev. 65, 1784–1802 (2013). https://doi.org/10.1016/j.addr.2013.07.012
  13. Y. Chang, K. Yang, P. Wei, S. Huang, Y. Pei, W. Zhao, Z. Pei, Cationic vesicles based on amphiphilic Pillar [5] arene capped with ferrocenium: a redox-responsive system for drug/siRNA co-delivery. Angew. Chem. Int. Ed. 53(48), 13126–13130 (2014). https://doi.org/10.1002/anie.201407272
  14. J.L. Shen, W. Zhang, R.G. Qi, Z.W. Mao, H.F. Shen, Engineering functional inorganic-organic hybrid systems: advances in siRNA therapeutics. Chem. Soc. Rev. 47, 1969–1995 (2018). https://doi.org/10.1039/C7CS00479F
  15. C.B. He, K.D. Lu, D.M. Liu, W.B. Lin, Nanoscale metal-organic frameworks for the co-delivery of cisplatin and pooled siRNAs to enhance therapeutic efficacy in drug-resistant ovarian cancer cells. J. Am. Chem. Soc. 136(14), 5181–5184 (2014). https://doi.org/10.1021/ja4098862
  16. C.B. He, C. Poon, C. Chan, S.D. Yamada, W.B. Lin, Nanoscale coordination polymers codeliver chemotherapeutics and siRNAs to eradicate tumors of cisplatin-resistant ovarian cancer. J. Am. Chem. Soc. 138(18), 6010–6019 (2016). https://doi.org/10.1021/jacs.6b02486
  17. M. Wu, Q. Meng, Y. Chen, L. Zhang, M. Li et al., Large pore-sized hollow mesoporous organosilica for redox-responsive gene delivery and synergistic cancer chemotherapy. Adv. Mater. 28, 1963–1969 (2016). https://doi.org/10.1002/adma.201505524
  18. J.L. Shen, H.C. Kim, H. Su, F. Wang, J. Wolfram et al., Cyclodextrin and polyethylenimine functionalized mesoporous silica nanoparticles for delivery of siRNA cancer therapeutics. Theranostics 4(5), 487–497 (2014). https://doi.org/10.7150/thno.8263
  19. J.L. Shen, R. Xu, J.H. Mai, H.C. Kim, X.J. Guo et al., High capacity nanoporous silicon carrier for systemic delivery of gene silencing therapeutics. ACS Nano 7(11), 9867–9880 (2013). https://doi.org/10.1021/nn4035316
  20. Y. Liu, V. Gunda, X. Zhu, X. Xu, J. Wu et al., Theranostic near-infrared fluorescent nanoplatform for imaging and systemic siRNA delivery to metastatic anaplastic thyroid cancer. Proc. Natl. Acad. Sci. U.S.A. 113(28), 7750–7755 (2016). https://doi.org/10.1073/pnas.1605841113
  21. R. Wang, L. Zhou, W.X. Wang, X.M. Li, F. Zhang, In vivo gastrointestinal drug-release monitoring through second near-infrared window fluorescent bioimaging with orally delivered microcarriers. Nat. Commun. 8, 14702 (2017). https://doi.org/10.1038/ncomms14702
  22. S. Kim, Y. Choi, G. Park, C. Won, Y.-J. Park, Y. Lee, B.-S. Kim, D.-H. Min, Highly efficient gene silencing and bioimaging based on fluorescent carbon dots in vitro and in vivo. Nano Res. 10(2), 503–519 (2017). https://doi.org/10.1007/s12274-016-1309-1
  23. F. Peng, Y.Y. Su, Y.L. Zhong, C.H. Fan, S.T. Lee, Y. He, Silicon nanomaterials platform for bioimaging, biosensing, and cancer therapy. Acc. Chem. Res. 47(2), 612–623 (2014). https://doi.org/10.1021/ar400221g
  24. M. Montalti, A. Cantelli, G. Battistelli, Nanodiamonds and silicon quantum dots: ultrastable and biocompatible luminescent nanoprobes for long-term bioimaging. Chem. Soc. Rev. 44, 4853–4921 (2015). https://doi.org/10.1039/C4CS00486H
  25. Y.Y. Su, X.Y. Ji, Y. He, Water-dispersible fluorescent silicon nanoparticles and their optical applications. Adv. Mater. 28(47), 10567–10574 (2016). https://doi.org/10.1002/adma.201601173
  26. C.X. Song, Y.L. Zhong, X.X. Jiang, F. Peng, Y.M. Lu et al., Peptide-conjugated fluorescent silicon nanoparticles enabling simultaneous tracking and specific destruction of cancer cells. Anal. Chem. 87(13), 6718–6723 (2015). https://doi.org/10.1021/acs.analchem.5b00853
  27. B.B. Chu, H.Y. Wang, B. Song, F. Peng, Y.Y. Su, Y. He, Fluorescent and photostable silicon nanoparticles sensors for real-time and long-term intracellular pH measurement in live cells. Anal. Chem. 88(18), 9235–9242 (2016). https://doi.org/10.1021/acs.analchem.6b02488
  28. X.Y. Ji, F. Peng, Y.L. Zhong, Y.Y. Su, X.X. Jiang et al., Highly fluorescent, photostable, and ultrasmall silicon drug nanocarriers for long-term tumor cell tracking and in vivo cancer therapy. Adv. Mater. 27(6), 1029–1034 (2015). https://doi.org/10.1002/adma.201403848
  29. Y.L. Zhong, X.T. Sun, S.Y. Wang, F. Peng, F. Bao et al., Large-quantity synthesis of stable, tunable-color silicon nanoparticles and their application for long-term cellular imaging. ACS Nano 9(6), 5958–5967 (2015). https://doi.org/10.1021/acsnano.5b00683
  30. C.A. Schneider, W.S. Rasband, K.W. Eliceiri, NIH image to imageJ: 25 years of image analysis. Nat. Methods 9, 671–675 (2012). https://doi.org/10.1038/nmeth.2089
  31. M.E. Davis, J.E. Zuckerman, C.H.J. Choi, D. Seligson, A. Tolcher et al., Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 464, 1067–1070 (2010). https://doi.org/10.1038/nature08956
  32. Y. Tay, L. Yuan, D.T. Leong, Nature-inspired DNA nanosensor for real-time in situ detection of mRNA in living cells. ACS Nano 9(5), 5609–5617 (2015). https://doi.org/10.1021/acsnano.5b01954
  33. M.I. Setyawati, R.V. Kutty, D.T. Leong, DNA nanostructures carrying stoichiometrically definable antibodies. Small 12(40), 5601–5611 (2016). https://doi.org/10.1002/smll.201601669
  34. K.J. Zhou, Y.G. Wang, X.N. Huang, K. Luby-phelps, B.D. Sumer, J.M. Gao, Tunable, ultrasensitive pH-responsive nanoparticles targeting specific endocytic organelles in living cells. Angew. Chem. Int. Ed. 50(27), 6109–6114 (2011). https://doi.org/10.1002/anie.201100884
  35. D.H. Kim, L.M. Villeneuve, K.V. Morris, J.J. Rossi, Argonaute-1 directs siRNA-mediated transcriptional gene silencing in human cells. Nat. Struct. Mol. Biol. 13, 793–797 (2006). https://doi.org/10.1038/nsmb1142
  36. B. Scaggiante, B. Dapas, R. Farra, M. Grassi, G. Pozzato, G. Gabreile, C. Qiansante, G. Grassi, Improving siRNA bio-distribution and minimizing side effects. Curr. Drug Metab. 12(1), 11–23 (2011). https://doi.org/10.2174/13892001179452001742
  37. M.I. Setyawati, C.Y. Tay, S.L. Chia, S.L. Goh, W. Fang, Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE-cadherin. Nat. Commun. 4, 1673 (2013). https://doi.org/10.1038/ncomms2655
  38. C.Y. Tay, M.I. Setyawati, D.T. Leong, Nanoparticle density: a critical biophysical regulator of endothelial permeability. ACS Nano 11(3), 2764–2772 (2017). https://doi.org/10.1021/acsnano.6b07806
  39. F. Peng, J.K. Tee, M.L. Setyawati, X.G. Ding, H.L.A. Yeo et al., Inorganic nanomaterials as highly efficient inhibitors of cellular hepatic fibrosis. ACS Appl. Mater. Interfaces. 10(38), 31938–31946 (2018). https://doi.org/10.1021/acsami.8b10527
  40. F. Peng, M.I. Setyawati, J.K. Tee, X.G. Ding, J.P. Wang et al., Nanoparticles promote in vivo breast cancer cell intravasation and extravasation by inducing endothelial leakiness. Nat. Nanotechnol. 14, 279–286 (2019). https://doi.org/10.1038/s41565-018-0356-z
Read More
Author biographies are not available.
Download this PDF file
PDF SUPPLEMENTARY MATERIAL
Statistic
Read Counter : 4603 Download : 3472

Most read articles by the same author(s)