Construction of Magnetic Resonance Imaging Visible Polymeric Vector for Efficient Tumor Targeted siRNA Delivery

Rong-Ze Wang; Si Huang; Qiao-Yun Zhang; Xing-Su Yu; Ke-Ze Hong; Jian-Rong Cao; Hong Xiao; Yong Wang; Xin-Tao Shuai

doi:10.1007/s10118-022-2794-1

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Construction of Magnetic Resonance Imaging Visible Polymeric Vector for Efficient Tumor Targeted siRNA Delivery

RESEARCH ARTICLE | Updated：2022-08-19

- Construction of Magnetic Resonance Imaging Visible Polymeric Vector for Efficient Tumor Targeted siRNA Delivery
- Chinese Journal of Polymer Science Vol. 40, Issue 9, Pages: 1071-1079(2022)
- Affiliations：
  
  a.College of Chemistry and Materials Science, Jinan University, Guangzhou 510632, China
  b.Nanomedicine Research Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China
  c.Department of Reproductive Medical Center, Guangdong Women and Children Hospital, Guangzhou 511400, China
- Author bio：
  
  wangy488@jnu.edu.cn (Y.W.)
  shuaixt@mail.sysu.edu.cn (X.T.S.)
- Funds：
- DOI：10.1007/s10118-022-2794-1
  CLC：
- Received：01 April 2022，
  
  Revised：2022-05-01，
  
  Accepted：07 May 2022，
  
  Online First：12 July 2022，
  
  Published：01 September 2022
- Accepted：
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Wang, R. Z.; Huang, S.; Zhang, Q. Y.; Yu, X. S.; Hong, K. Z.; Cao, J. R.; Xiao, H.; Wang, Y.; Shuai, X. T. Construction of magnetic resonance imaging visible polymeric vector for efficient tumor targeted siRNA delivery. Chinese J. Polym. Sci. 2022, 40, 1071–1079

Rong-Ze Wang, Si Huang, Qiao-Yun Zhang, et al. Construction of Magnetic Resonance Imaging Visible Polymeric Vector for Efficient Tumor Targeted siRNA Delivery[J]. Chinese Journal of Polymer Science, 2022, 40(9): 1071-1079.
Wang, R. Z.; Huang, S.; Zhang, Q. Y.; Yu, X. S.; Hong, K. Z.; Cao, J. R.; Xiao, H.; Wang, Y.; Shuai, X. T. Construction of magnetic resonance imaging visible polymeric vector for efficient tumor targeted siRNA delivery. Chinese J. Polym. Sci. 2022, 40, 1071–1079 DOI： 10.1007/s10118-022-2794-1.

Rong-Ze Wang, Si Huang, Qiao-Yun Zhang, et al. Construction of Magnetic Resonance Imaging Visible Polymeric Vector for Efficient Tumor Targeted siRNA Delivery[J]. Chinese Journal of Polymer Science, 2022, 40(9): 1071-1079. DOI： 10.1007/s10118-022-2794-1.

摘要

We propose a cationic block polymer based on polyethylene glycol and poly aspartic acid for siRNA delivery. The vector exerts multi properties including good biocompatibility

high encapsulation efficiency

and tailorable modification for superparamagnetic iron oxide and targeting components

which result in a highly efficient and tumor targeted siRNA delivery.

Abstract

RNA interference (RNAi)

known for the highly efficient targeted gene silencing

has been demonstrated to be a promising means for cancer treatment. Meanwhile

an effective approach for siRNA delivery is urgently needed to meet the needs for its clinical application. Herein

we constructed a polymeric vector labeled with superparamagnetic iron oxide (SPIO) for magnetic resonance imaging (MRI) visible siRNA delivery. EGFR antibody was also modified to the surface of nanodrug to enhance the delivery effect. Our results showed that the vector exhibited great siRNA complexation ability and mediated an increased endocytosis of siRNA without obvious cytotoxicity. Besides

both

in vitro

and

in vivo

studies evidenced the vector could effectively deliver siRNA into tumor cells

exert highly interfering effect

and show potent MR imaging capacity. The study provides a promising MRI-visible and EGFR targeting delivery system to improve RNAi efficacy for cancer therapy.

关键词

Keywords

references

Fire, A.; Xu, S.; Montgomery, M. K.; Kostas, S. A.; Driver, S. E.; Mello, C. C . Potent and specific genetic interference by double-stranded RNA in caenorhabditis elegans . Nature , 1998 . 391 806 - 811 . DOI: 10.1038/35888 http://doi.org/10.1038/35888 .

Hattab, D.; Gazzali, A. M.; Bakhtiar, A . Clinical advances of siRNA-based nanotherapeutics for cancer treatment . Pharmaceutics , 2021 . 13 1009 DOI: 10.3390/pharmaceutics13071009 http://doi.org/10.3390/pharmaceutics13071009 .

Xin, Y.; Huang, M.; Guo, W . W.; Huang, Q.; Jiang, G. Nano-based delivery of RNAi in cancer therapy . Mol. Cancer , 2017 . 16 1 - 9 . .

Koren, M. J.; Moriarty, P. M.; Baum, S. J.; Neutel, J.; Hernandez-Illas, M.; Weintraub, H. S.; Florio, M.; Kassahun, H.; Melquist, S.; Varrieur, T . Preclinical development and phase 1 trial of a novel siRNA targeting lipoprotein(a) . Nat. Med. , 2022 . 28 96 - 103 . DOI: 10.1038/s41591-021-01634-w http://doi.org/10.1038/s41591-021-01634-w .

Mishra, N.; Ashique, S.; Garg, A.; Rai, V. K.; Dua, K.; Goyal, A.; Bhatt, S . Role of siRNA-based nanocarriers for the treatment of neurodegenerative diseases . Drug Discov. Today , 2022 . 27 1431 - 1440 . DOI: 10.1016/j.drudis.2022.01.003 http://doi.org/10.1016/j.drudis.2022.01.003 .

Bäumer, N.; Tiemann, J.; Scheller, A.; Meyer, T.; Wittmann, L.; Suburu, M. E. G.; Greune, L.; Peipp, M.; Kellmann, N.; Gumnior, A . Targeted siRNA nanocarrier: a platform technology for cancer treatment . Oncogene , 2022 . 41 2210 - 2224 . DOI: 10.1038/s41388-022-02241-w http://doi.org/10.1038/s41388-022-02241-w .

Hang, Y.; Tang, S. Y.; Tang, W. M.; Větvička, D.; Zhang, C. H.; Xie, Y.; Yu, F.; Yu, A.O.; Sil, D.; Li, J.; Singh. R. K.; Oupicky, D . Polycation fluorination improves intraperitoneal siRNA delivery in metastatic pancreatic cancer . J. Control. Rel. , 2021 . 333 139 - 150 . DOI: 10.1016/j.jconrel.2021.03.028 http://doi.org/10.1016/j.jconrel.2021.03.028 .

Idris, A.; Davis, A.; Supramaniam, A.; Acharya, D.; Kelly, G.; Tayyar, Y.; West, N.; Zhang, P.; McMillan, C. L. D ; Soemardy, C . A SARS-CoV-2 targeted siRNA-nanoparticle therapy for COVID-19 . Mol. Ther. , 2021 . 29 2219 - 2226 . DOI: 10.1016/j.ymthe.2021.05.004 http://doi.org/10.1016/j.ymthe.2021.05.004 .

Alshaer, W.; Zureigat, H.; Al Karaki, A.; Al-Kadash, A.; Gharaibeh, L.; Ma'mon, M. H.; Aljabali, A. A.; Awidi, A . siRNA: Mechanism of action, challenges, and therapeutic approaches . Eur. J. Pharmacol. , 2021 . 905 174178 DOI: 10.1016/j.ejphar.2021.174178 http://doi.org/10.1016/j.ejphar.2021.174178 .

Subhan, M. A.; Torchilin, V. P . Efficient nanocarriers of siRNA therapeutics for cancer treatment . Transl. Res. , 2019 . 214 62 - 91 . DOI: 10.1016/j.trsl.2019.07.006 http://doi.org/10.1016/j.trsl.2019.07.006 .

Wang, H.; Zhang, S.; Lv, J.; Cheng, Y. Y . Design of polymers for siRNA delivery: Recent progress and challenges . View , 2021 . 2 20200026 DOI: 10.1002/VIW.20200026 http://doi.org/10.1002/VIW.20200026 .

Chen, M. Y.; Dong, C. Y.; Shi, S . Nanoparticle-Mediated siRNA Delivery and Multifunctional Modification Strategies for Effective Cancer Therapy . Adv. Mater. Technol. , 2021 . 6 2001236 DOI: 10.1002/admt.202001236 http://doi.org/10.1002/admt.202001236 .

Kondinskaia, D. A.; Gurtovenko, A. A . Supramolecular complexes of DNA with cationic polymers: the effect of polymer concentration . Polymer , 2018 . 142 277 - 284 . DOI: 10.1016/j.polymer.2018.03.048 http://doi.org/10.1016/j.polymer.2018.03.048 .

Osipova, O.; Sharoyko, V.; Zashikhina, N.; Zakharova, N.; Tennikova, T.; Urtti, A.; Korzhikova-Vlakh, E . Amphiphilic polypeptides for VEGF siRNA delivery into retinal epithelial cells . Pharmaceutics , 2020 . 12 39 DOI: 10.3390/pharmaceutics12010039 http://doi.org/10.3390/pharmaceutics12010039 .

Xue, L.; Yan, Y. F.; Kos, P.; Chen, X. P.; Siegwart, D. J . PEI fluorination reduces toxicity and promotes liver-targeted siRNA delivery . Drug Deliv. Transl. Res. , 2021 . 11 255 - 260 . DOI: 10.1007/s13346-020-00790-9 http://doi.org/10.1007/s13346-020-00790-9 .

Islam, M. A.; Park, T. E.; Singh, B.; Maharjan, S.; Firdous, J.; Cho, M. H.; Kang, S. K.; Yun, C. H.; Choi, Y. J.; Cho, C. S . Major degradable polycations as carriers for DNA and siRNA . J. Control. Rel. , 2014 . 193 74 - 89 . DOI: 10.1016/j.jconrel.2014.05.055 http://doi.org/10.1016/j.jconrel.2014.05.055 .

Zhang, L. M.; Lu, Z. X.; Zhao, Q. H; Huang, J.; Shen, H.; Zhang, Z. J . Enhanced chemotherapy efficacy by sequential delivery of siRNA and anticancer drugs using PEI-grafted graphene oxide . Small , 2011 . 7 460 - 464 . DOI: 10.1002/smll.201001522 http://doi.org/10.1002/smll.201001522 .

Yu, J. H.; Quan, J. S.; Huang, J.; Wang, C. Y.; Sun, B.; Nah, J. W.; Cho, M. H.; Cho, C. S . α , β -Poly(l-aspartate-graft-PEI): a pseudo-branched PEI as a gene carrier with low toxicity and high transfection efficiency . Acta Biomater. , 2009 . 5 2485 - 2494 . DOI: 10.1016/j.actbio.2009.03.012 http://doi.org/10.1016/j.actbio.2009.03.012 .

Zintchenko, A.; Philipp, A.; Dehshahri, A.; Wagner, E . Simple modifications of branched PEI lead to highly efficient siRNA carriers with low toxicity . Bioconjugate Chem. , 2008 . 19 1448 - 1455 . DOI: 10.1021/bc800065f http://doi.org/10.1021/bc800065f .

Dai, Z. J.; Gjetting, T.; Mattebjerg, M. A.; Wu, C.; Andresen, T. L . Elucidating the interplay between DNA-condensing and free polycations in gene transfection through a mechanistic study of linear and branched PEI . Biomaterials , 2011 . 32 8626 - 8634 . DOI: 10.1016/j.biomaterials.2011.07.044 http://doi.org/10.1016/j.biomaterials.2011.07.044 .

Li, W.G.; Zhang, Z. L.; Gordon, A. C.; Chen, J.; Nicolai, J.; Lewandowski, R. J.; Omary, R. A.; Larson, A. C . SPIO-labeled yttrium microspheres for MR imaging quantification of transcatheter intrahepatic delivery in a rodent model . Radiology , 2016 . 278 405 - 412 . DOI: 10.1148/radiol.2015150315 http://doi.org/10.1148/radiol.2015150315 .

Lu, H.W.; Xu, Y. J.; Qiao, R. R.; Lu, Z. W.; Wang, P.; Zhang, X. D.; Chen, A.; Zou, L. M.; Wang, Z. L . A novel clustered SPIO nanoplatform with enhanced magnetic resonance T2 relaxation rate for micro-tumor detection and photothermal synergistic therapy . Nano Res. , 2020 . 13 2216 - 2225 . DOI: 10.1007/s12274-020-2839-0 http://doi.org/10.1007/s12274-020-2839-0 .

Guo, Y.; Chen, W. J.; Wang, W. W.; Shen, J.; Guo, R. M.; Gong, F. M.; Lin, S. D; Cheng, D.; Chen, G. H.; Shuai, X. T . Simultaneous diagnosis and gene therapy of immuno-rejection in rat allogeneic heart transplantation model using a T-cell-targeted theranostic nanosystem . ACS Nano. , 2012 . 6 10646 - 10657 . DOI: 10.1021/nn3037573 http://doi.org/10.1021/nn3037573 .

Guo, Y.; Wang, J.; Zhang, L.; Shen, S. L.; Guo, R.M; Yang, Y.; Chen, W. J.; Wang, Y. R; Chen, G. H.; Shuai, X. T . Theranostical nanosystem-mediated identification of an oncogene and highly effective therapy in hepatocellular carcinoma . Hepatology , 2016 . 63 1240 - 1255 . DOI: 10.1002/hep.28409 http://doi.org/10.1002/hep.28409 .

Guo, Y.; Wu, Z. Q.; Shen, S. L.; Guo, R. M.; Wang, J.; Wang, W. W.; Zhao, K.; Kuang, M.; Shuai, X. T . Nanomedicines reveal how PBOV1 promotes hepatocellular carcinoma for effective gene therapy . Nat. Commun. , 2018 . 9 1 - 16 . DOI: 10.1038/s41467-017-02088-w http://doi.org/10.1038/s41467-017-02088-w .

Yadav, D.; Dewangan, H. K . PEGYLATION: an important approach for novel drug delivery system . J. Biomat. Sci. Polym. E , 2021 . 32 266 - 280 . DOI: 10.1080/09205063.2020.1825304 http://doi.org/10.1080/09205063.2020.1825304 .

Hussain, Z.; Khan, S.; Imran, M.; Sohail, M.; Shah, S. W. A.; de Matas, M . PEGylation: A promising strategy to overcome challenges to cancer-targeted nanomedicines: a review of challenges to clinical transition and promising resolution . Drug Deliv. Transl. Res. , 2019 . 9 721 - 734 . DOI: 10.1007/s13346-019-00631-4 http://doi.org/10.1007/s13346-019-00631-4 .

Mozar, F. S.; Chowdhury, E. H . Impact of PEGylated nanoparticles on tumor targeted drug delivery . Curr. Pharm. Design , 2018 . 24 3283 - 3296 . DOI: 10.2174/1381612824666180730161721 http://doi.org/10.2174/1381612824666180730161721 .

Dai, J. A.; Zou, S. Y.; Pei, Y. Y.; Cheng, D.; Ai, H.; Shuai, X. T . Polyethylenimine-grafted copolymer of poly(l-lysine) and poly(ethylene glycol) for gene delivery . Biomaterials , 2011 . 32 1694 - 1705 . DOI: 10.1016/j.biomaterials.2010.10.044 http://doi.org/10.1016/j.biomaterials.2010.10.044 .

Li, J. G.; Cheng, D.; Yin, T. H.; Chen, W. C.; Lin, Y. J.; Chen, J. F.; Li, R. T.; Shuai, X. T . Copolymer of poly(ethylene glycol) and poly(L-lysine) grafting polyethylenimine through a reducible disulfide linkage for siRNA delivery . Nanoscale , 2014 . 6 1732 - 1740 . DOI: 10.1039/C3NR05024F http://doi.org/10.1039/C3NR05024F .

Li, J. G.; Yu, X. S.; Wang, Y.; Yuan, Y. Y.; Xiao, H.; Cheng, D.; Shuai, X. T . A reduction and pH dual-sensitive polymeric vector for long-circulating and tumor-targeted siRNA delivery . Adv. Mater. , 2014 . 26 8217 - 8224 . DOI: 10.1002/adma.201403877 http://doi.org/10.1002/adma.201403877 .

Wang, Y.; Xiao, H.; Fang, J.; Yu, X. S.; Su, Z. W.; Cheng, D.; Shuai, X. T . Construction of negatively charged and environment-sensitive nanomedicine for tumor-targeted efficient siRNA delivery . Chem. Commun. , 2016 . 52 1194 - 1197 . DOI: 10.1039/C5CC09181K http://doi.org/10.1039/C5CC09181K .

He, H.; Chen, Y. B.; Li, Y. J.; Song, Z. Y.; Zhong, Y. N.; Zhu, R. Y.; Cheng, J. J.; Yin, L. C . Effective and selective anti-cancer protein delivery via all-functions-in-one nanocarriers coupled with visible light-responsive, reversible protein engineering . Adv. Funct. Mater. , 2018 . 28 1706710 DOI: 10.1002/adfm.201706710 http://doi.org/10.1002/adfm.201706710 .

Karachaliou, N.; Fernandez-Bruno, M.; Bracht, J. W. P.; Rosell, R . EGFR first-and second-generation TKIs-there is still place for them in EGFR-mutant NSCLC patients . Transl. Cancer Res. , 2019 . 8 S23 DOI: 10.21037/tcr.2018.12.27 http://doi.org/10.21037/tcr.2018.12.27 .

Sun, S. H.; Zeng, H.; Robinson, D. B.; Raoux, S.; Rice, P. M.; Wang, S. X.; Li, G. X . Monodisperse MFe 2 O 4 (M= Fe, Co, Mn) nanoparticles . J. Am. Chem. Soc. , 2004 . 126 273 - 279 . DOI: 10.1021/ja0380852 http://doi.org/10.1021/ja0380852 .

Li, B.; Cai, M. Y.; Lin, L. T.; Sun, W. T.; Zhou, Z. M.; Wang, S. Y.; Wang, Y.; Zhu, K. S.; Shuai, X. T . MRI-visible and pH-sensitive micelles loaded with doxorubicin for hepatoma treatment . Biomater. Sci. , 2019 . 7 1529 - 1542 . DOI: 10.1039/C8BM01501E http://doi.org/10.1039/C8BM01501E .

Zhong, Y.; Huang, S.; Zheng, C. J.; Huang, J. S.; Li, B.; Han, S. S.; Xiao, H.; Wang, Y.; Shuai, X. T . A light and hypoxia-activated nanodrug for cascade photodynamic-chemo cancer therapy . Biomater. Sci. , 2021 . 9 5218 - 5226 . DOI: 10.1039/D1BM00660F http://doi.org/10.1039/D1BM00660F .

Pu, Y. J.; Zhang, L. G.; Zheng, H.; He, B.; Gu, Z. W . Synthesis and drug release of star-shaped poly (benzyl l-aspartate)-block-poly (ethylene glycol) copolymers with POSS cores . Macromol. Biosci. , 2014 . 14 289 - 297 . DOI: 10.1002/mabi.201300270 http://doi.org/10.1002/mabi.201300270 .

Kwok, A.; Hart, S. L . Comparative structural and functional studies of nanoparticle formulations for DNA and siRNA delivery . Nanomed.-Nanotechnol. , 2011 . 7 210 - 219 . DOI: 10.1016/j.nano.2010.07.005 http://doi.org/10.1016/j.nano.2010.07.005 .

Gill, K. K.; Kamal, M. M.; Kaddoumi, A.; Nazzal, S . EGFR targeted delivery of paclitaxel and parthenolide co-loaded in PEG-Phospholipid micelles enhance cytotoxicity and cellular uptake in non-small cell lung cancer cells . J. Drug Deliv. Sci. Technol. , 2016 . 36 150 - 155 . DOI: 10.1016/j.jddst.2016.10.005 http://doi.org/10.1016/j.jddst.2016.10.005 .

Tong, S.; Hou, S. J.; Zheng, Z . L.; Zhou, J.; Bao, G. Coating optimization of superparamagnetic iron oxide nanoparticles for high T2 relaxivity . Nano Lett. , 2010 . 10 4607 - 4613 . DOI: 10.1021/nl102623x http://doi.org/10.1021/nl102623x .

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