Journal Home > Volume 13 , Issue 1
Nano Research 2020, 13(1): 273-281 https://doi.org/10.1007/s12274-019-2610-6
Research Article | Issue | Published: 02 January 2020

PCN-Fe(III)-PTX nanoparticles for MRI guided high efficiency chemo-photodynamic therapy in pancreatic cancer through alleviating tumor hypoxia

Show Author's Information Tao Zhang1,§,  Zhenqi Jiang2,3,§,  Libin Chen4,§,  Chunshu Pan2,  Shan Sun2,  Chuang Liu2,  Zihou Li2,  Wenzhi Ren2,5( ),  Aiguo Wu2( ),  Pintong Huang1( )
Department of Ultrasound, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China
Cixi Institute of Biomedical Engineering, CAS Key Laboratory of Magnetic Materials and Devices, & Key Laboratory of Additive Manufacturing Materials of Zhejiang Province, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, China
University of Chinese Academy of Sciences, Beijing 100049, China
Department of Ultrasound, Ningbo First Hospital, Ningbo 315010, China
Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo 315016, China

§ Tao Zhang, Zhenqi Jiang, and Libin Chen contributed equally to this work.

Keywords:
hypoxia, photodynamic therapy, porous-coordination polymers, magnetic resonance imaging (MRI) imaging, chemocherapy
Topics:
Cell cultureChemotherapy Controlled drug deliveryDiseasesMagnetic resonance imagingMedical nanotechnologyNanoparticlesOxidationOxygenTargeted drug deliveryTumors
Cite this article:
Zhang T, Jiang Z, Chen L, et al. PCN-Fe(III)-PTX nanoparticles for MRI guided high efficiency chemo-photodynamic therapy in pancreatic cancer through alleviating tumor hypoxia. Nano Research, 2020, 13(1): 273-281. https://doi.org/10.1007/s12274-019-2610-6
Download citation
EndNote(RIS)
BibTeX

761

Views

24

Downloads

Citations

53

Crossref

N/A

WoS

54

Scopus

7

CSCD

Abstract Full text Electronic supplementary material About this article

As nanomedicine-based clinical strategies have continued to develop, the possibility of combining chemotherapy and singlet oxygen-dependent photodynamic therapy (PDT) to treat pancreatic cancer (PaC) has emerged as a viable therapeutic modality. The efficacy of such an approach, however, is likely to be constrained by the mechanisms of drug release and tumor oxygen levels. In the present study, we developed an Fe(III)-complexed porous coordination network (PCN) which we then used to encapsulate PTX (PCN-Fe(III)-PTX) nanoparticles (NPs) in order to treat PaC via a combination of chemotherapy and PDT. The resultant NPs were able to release drug in response to both laser irradiation and pH changes to promote drug accumulation within tumors. Furthermore, through a Fe(III)-based Fenton-like reaction these NPs were able to convert H2O2 in the tumor site to O2, thereby regulating local hypoxic conditions and enhancing the efficacy of PDT approaches. Also these NPs were suitable for use as a T1-magnetic resonance imaging (MRI) weighted contrast agent, making them viable for monitoring therapeutic efficacy upon treatment. Our results in both cell line and animal models of PaC suggest that these NPs represent an ideal agent for mediating effective MRI-guided chemotherapy-PDT, giving them great promise for the clinical treatment of PaC.


menu
Abstract
Full text
Outline
Electronic supplementary material
About this article

PCN-Fe(III)-PTX nanoparticles for MRI guided high efficiency chemo-photodynamic therapy in pancreatic cancer through alleviating tumor hypoxia

Show Author's information Tao Zhang1,§, Zhenqi Jiang2,3,§, Libin Chen4,§, Chunshu Pan2, Shan Sun2, Chuang Liu2, Zihou Li2, Wenzhi Ren2,5( ), Aiguo Wu2( ), Pintong Huang1( )
Department of Ultrasound, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China
Cixi Institute of Biomedical Engineering, CAS Key Laboratory of Magnetic Materials and Devices, & Key Laboratory of Additive Manufacturing Materials of Zhejiang Province, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, China
University of Chinese Academy of Sciences, Beijing 100049, China
Department of Ultrasound, Ningbo First Hospital, Ningbo 315010, China
Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo 315016, China

§ Tao Zhang, Zhenqi Jiang, and Libin Chen contributed equally to this work.

Abstract

As nanomedicine-based clinical strategies have continued to develop, the possibility of combining chemotherapy and singlet oxygen-dependent photodynamic therapy (PDT) to treat pancreatic cancer (PaC) has emerged as a viable therapeutic modality. The efficacy of such an approach, however, is likely to be constrained by the mechanisms of drug release and tumor oxygen levels. In the present study, we developed an Fe(III)-complexed porous coordination network (PCN) which we then used to encapsulate PTX (PCN-Fe(III)-PTX) nanoparticles (NPs) in order to treat PaC via a combination of chemotherapy and PDT. The resultant NPs were able to release drug in response to both laser irradiation and pH changes to promote drug accumulation within tumors. Furthermore, through a Fe(III)-based Fenton-like reaction these NPs were able to convert H2O2 in the tumor site to O2, thereby regulating local hypoxic conditions and enhancing the efficacy of PDT approaches. Also these NPs were suitable for use as a T1-magnetic resonance imaging (MRI) weighted contrast agent, making them viable for monitoring therapeutic efficacy upon treatment. Our results in both cell line and animal models of PaC suggest that these NPs represent an ideal agent for mediating effective MRI-guided chemotherapy-PDT, giving them great promise for the clinical treatment of PaC.

Keywords: hypoxia, photodynamic therapy, porous-coordination polymers, magnetic resonance imaging (MRI) imaging, chemocherapy

References(38)

[1]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R. L.; Torre, L. A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2016, 68, 394-424.
DOI Google Scholar
[2]
Kamisawa, T.; Wood, L. D.; Itoi, T.; Takaori, K. Pancreatic cancer. Lancet 2016, 388, 73-85.
DOI Google Scholar
[3]
Witkowski, E. R.; Smith, J. K.; Tseng, J. F. Outcomes following resection of pancreatic cancer. J. Surg. Oncol. 2013, 107, 97-103.
DOI Google Scholar
[4]
Von Hoff, D. D.; Ervin, T.; Arena, F. P.; Chiorean, E. G.; Infante, J.; Moore, M.; Seay, T.; Tjulandin, S. A.; Ma, W. W.; Saleh, M. N. et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N. Engl. J. Med. 2013, 369, 1691-1703.
DOI Google Scholar
[5]
Gelderblom, H.; Verweij, J.; Nooter, K.; Sparreboom, A. Cremophor EL: The drawbacks and advantages of vehicle selection for drug formulation. Eur. J. Cancer 2001, 37, 1590-1598.
DOI Google Scholar
[6]
Zhang, F. W.; Zhang, S. Y.; Pollack, S. F.; Li, R. C.; Gonzalez, A. M.; Fan, J. W.; Zou, J.; Leininger, S. E.; Pavía-Sanders, A.; Johnson, R. et al. Improving paclitaxel delivery: In vitro and in vivo characterization of PEGylated polyphosphoester-based nanocarriers. J. Am. Chem. Soc. 2015, 137, 2056-2066.
DOI Google Scholar
[7]
Feng, Q. H.; Zhang, W. X.; Yang, X. M.; Li, Y. Z.; Hao, Y. W.; Zhang, H. L.; Hou, L.; Zhang, Z. Z. pH/ultrasound dual-responsive gas generator for ultrasound imaging-guided therapeutic inertial cavitation and sonodynamic therapy. Adv. Healthc. Mater.. 2018, 7, 1700957.
DOI Google Scholar
[8]
Chen, W. H.; Luo, G. F.; Vázquez-González, M.; Cazelles, R.; Sohn, Y. S.; Nechushtai, R.; Mandel, Y.; Willner, I. Glucose-responsive metal-organic-framework nanoparticles act as “smart” sense-and-treat carriers. ACS Nano 2018, 12, 7538-7545.
DOI Google Scholar
[9]
Bansal, A.; Zhang, Y. Photocontrolled nanoparticle delivery systems for biomedical applications. Acc. Chem. Res. 2014, 47, 3052-3060.
DOI Google Scholar
[10]
Lee, H.; Han, J.; Shin, H.; Han, H.; Na, K.; Kim, H. Combination of chemotherapy and photodynamic therapy for cancer treatment with sonoporation effects. J. Control. Release 2018, 283, 190-199.
DOI Google Scholar
[11]
Jiang, Z. Q.; Wang, Y. J.; Sun, L.; Yuan, B.; Tian, Y. C.; Xiang, L. C.; Li, Y. Y.; Li, Y.; Li, J.; Wu, A. G. Dual ATP and pH responsive ZIF-90 nanosystem with favorable biocompatibility and facile post-modification improves therapeutic outcomes of triple negative breast cancer in vivo. Biomaterials 2019, 197, 41-50.
DOI Google Scholar
[12]
Jiang, Z. Q.; Yuan, B.; Qiu, N. X.; Wang, Y. J.; Sun, L.; Wei, Z. N.; Li, Y. Y.; Zheng, J. J.; Jin, Y. H.; Li, Y. et al. Manganese-zeolitic imidazolate frameworks-90 with high blood circulation stability for MRI-guided tumor therapy. Nano-Micro Lett. 2019, 11, 61.
DOI Google Scholar
[13]
Spring, B. Q.; Rizvi, I.; Xu, N.; Hasan, T. The role of photodynamic therapy in overcoming cancer drug resistance. Photochem. Photobiol. Sci. 2015, 14, 1476-1491.
DOI Google Scholar
[14]
Zhao, Y. Y.; Wei, C. F.; Chen, X.; Liu, J. W.; Yu, Q. Q.; Liu, Y. N.; Liu, J. Drug delivery system based on near-infrared light-responsive molybdenum disulfide nanosheets controls the high-efficiency release of dexamethasone to inhibit inflammation and treat osteoarthritis. ACS Appl. Mater. Interfaces 2019, 11, 11587-11601.
DOI Google Scholar
[15]
Bown, S. G.; Rogowska, A. Z.; Whitelaw, D. E.; Lees, W. R.; Lovat, L. B.; Ripley, P.; Jones, L.; Wyld, P.; Gillams, A.; Hatfield, A. W. R. Photodynamic therapy for cancer of the pancreas. Gut 2002, 50, 549-557.
DOI Google Scholar
[16]
Hu, D. H.; Chen, Z. W.; Sheng, Z. H.; Gao, D. Y.; Yan, F.; Ma, T.; Zheng, H. R.; Hong, M. A catalase-loaded hierarchical zeolite as an implantable nanocapsule for ultrasound-guided oxygen self-sufficient photodynamic therapy against pancreatic cancer. Nanoscale 2018, 10, 17283-17292.
DOI Google Scholar
[17]
Xu, R. Y.; Wang, Y. F.; Duan, X. P.; Lu, K. D.; Micheroni, D.; Hu, A. G.; Lin, W. B. Nanoscale metal-organic frameworks for ratiometric oxygen sensing in live cells. J. Am. Chem. Soc. 2016, 138, 2158-2161.
DOI Google Scholar
[18]
Yang, G. B.; Xu, L. G.; Chao, Y.; Xu, J.; Sun, X. Q.; Wu, Y. F.; Peng, R.; Liu, Z. Hollow MnO2 as a tumor-microenvironment-responsive biodegradable nano-platform for combination therapy favoring antitumor immune responses. Nat. Commun. 2017, 8, 902.
DOI Google Scholar
[19]
Bristow, R. G.; Hill, R. P. Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat. Rev. Cancer 2008, 8, 180-192.
DOI Google Scholar
[20]
Wang, D. D.; Wu, H. H.; Lim, W. Q.; Phua, S. Z. F.; Xu, P. P.; Chen, Q. W.; Guo, Z.; Zhao, Y. L. A mesoporous nanoenzyme derived from metal-organic frameworks with endogenous oxygen generation to alleviate tumor hypoxia for significantly enhanced photodynamic therapy. Adv. Mater. 2019, 31, 1901893.
DOI Google Scholar
[21]
Tang, J. Q.; Zhou, H. G.; Hou, X. Y.; Wang, L. M.; Li, Y. X.; Pang, Y. Y.; Chen, C. Y.; Jiang, G.; Liu, Y. Q. Enhanced anti-tumor efficacy of temozolomide-loaded carboxylated poly(amido-amine) combined with photothermal/photodynamic therapy for melanoma treatment. Cancer Lett. 2018, 423, 16-26.
DOI Google Scholar
[22]
You, Q.; Sun, Q.; Wang, J. P.; Tan, X. X.; Pang, X. J.; Liu, L.; Yu, M.; Tan, F. P.; Li, N. A single-light triggered and dual-imaging guided multifunctional platform for combined photothermal and photodynamic therapy based on TD-controlled and ICG-loaded CuS@mSiO2. Nanoscale 2017, 9, 3784-3796.
DOI Google Scholar
[23]
Cheng, Y. H.; Cheng, H.; Jiang, C. X.; Qiu, X. F.; Wang, K. K.; Huan, W.; Yuan, A. H.; Wu, J. H.; Hu, Y. Q. Perfluorocarbon nanoparticles enhance reactive oxygen levels and tumour growth inhibition in photodynamic therapy. Nat. Commun. 2015, 6, 8785.
DOI Google Scholar
[24]
Liu, L. H.; Zhang, Y. H.; Qiu, W. X.; Zhang, L.; Gao, F.; Li, B.; Xu, L.; Fan, J. X.; Li, Z. H.; Zhang, X. Z. Dual-stage light amplified photodynamic therapy against hypoxic tumor based on an O2 self-sufficient nanoplatform. Small 2017, 13, 1701621.
DOI Google Scholar
[25]
McEwan, C.; Owen, J.; Stride, E.; Fowley, C.; Nesbitt, H.; Cochrane, D.; Coussios, C. C.; Borden, M.; Nomikou, N.; McHale, A. P. et al. Oxygen carrying microbubbles for enhanced sonodynamic therapy of hypoxic tumours. J. Control. Release 2015, 203, 51-56.
DOI Google Scholar
[26]
Halliwell, B.; Clement, M. V.; Long, L. H. Hydrogen peroxide in the human body. FEBS Lett. 2000, 486, 10-13.
DOI Google Scholar
[27]
Valko, M.; Izakovic, M.; Mazur, M.; Rhodes, C. J.; Telser, J. Role of oxygen radicals in DNA damage and cancer incidence. Mol. Cell. Biochem. 2004, 266, 37-56.
DOI Google Scholar
[28]
Ma, Z. F.; Zhang, M. C.; Jia, X. D.; Bai, J.; Ruan, Y. D.; Wang, C.; Sun, X. P.; Jiang, X. E. FeIII-doped two-dimensional C3N4 nanofusiform: A new O2-evolving and mitochondria-targeting photodynamic agent for MRI and enhanced antitumor therapy. Small 2016, 12, 5477-5487.
DOI Google Scholar
[29]
Zheng, D. W.; Li, B.; Li, C. X.; Fan, J. X.; Lei, Q.; Li, C.; Xu, Z. S.; Zhang, X. Z. Carbon-dot-decorated carbon nitride nanoparticles for enhanced photodynamic therapy against hypoxic tumor via water splitting. ACS Nano 2016, 10, 8715-8722.
DOI Google Scholar
[30]
Pinto, S. M. A.; Calvete, M. J. F.; Ghica, M. E.; Soler, S.; Gallardo, I.; Pallier, A.; Laranjo, M. B.; Cardoso, A. M. S.; Castro, M. M. C. A.; Brett, C. M. A. et al. A biocompatible redox MRI probe based on a Mn(II)/Mn(III) porphyrin. Dalton Trans. 2019, 48, 3249-3262.
DOI Google Scholar
[31]
Shen, Z. Y.; Song, J. B.; Yung, B. C.; Zhou, Z. J.; Wu, A. G.; Chen, X. Y. Emerging strategies of cancer therapy based on ferroptosis. Adv. Mater. 2018, 30, 1704007.
DOI Google Scholar
[32]
Lan, G. X.; Ni, K. Y.; Xu, Z. W.; Veroneau, S. S.; Song, Y.; Lin, W. B. Nanoscale metal-organic framework overcomes hypoxia for photodynamic therapy primed cancer immunotherapy. J. Am. Chem. Soc. 2018, 140, 5670-5673.
DOI Google Scholar
[33]
Wang, Y. J.; Wang, C.; Gong, C. Y.; Wang, Y. J.; Guo, G.; Luo, F.; Qian, Z. Y. Polysorbate 80 coated poly (ε-caprolactone)-poly (ethylene glycol)-poly (ε-caprolactone) micelles for paclitaxel delivery. Int. J. Pharm. 2012, 434, 1-8.
DOI Google Scholar
[34]
Garvie, L. A. J.; Buseck, P. R. Ratios of ferrous to ferric iron from nanometre-sized areas in minerals. Nature 1998, 396, 667-670.
DOI Google Scholar
[35]
Liu, C.; Luo, L. J.; Zeng, L. Y.; Xing, J.; Xia, Y. Z.; Sun, S.; Zhang, L. Y.; Yu, Z.; Yao, J. L.; Yu, Z. S. et al. Porous gold nanoshells on functional NH2-MOFs: Facile synthesis and designable platforms for cancer multiple therapy. Small 2018, 14, 1801851.
DOI Google Scholar
[36]
Sukhorukov, G. B.; Antipov, A. A.; Voigt, A.; Donath, E.; Möhwald, H. pH-controlled macromolecule encapsulation in and release from polyelectrolyte multilayer nanocapsules. Macromol. Rapid Commun. 2001, 22, 44-46.
DOI
[37]
Park, J.; Jiang, Q.; Feng, D. W.; Mao, L. Q.; Zhou, H. C. Size-controlled synthesis of porphyrinic metal-organic framework and functionalization for targeted photodynamic therapy. J. Am. Chem. Soc. 2016, 138, 3518-3525.
DOI Google Scholar
[38]
Fan, L.; Zhao, S. S.; Jin, X.; Zhang, Y. S.; Song, C. J.; Wu, H. Synergistic chemo-photodynamic therapy by “big & small combo nanoparticles” sequential release system. Nanomed.: Nanotechnol., Biol. Med. 2018, 14, 109-121.
DOI Google Scholar
File
12274_2019_2610_MOESM1_ESM.pdf (2.4 MB)
Publication history
Copyright
Acknowledgements

Publication history

Received: 19 October 2019
Revised: 11 December 2019
Accepted: 15 December 2019
Published: 02 January 2020
Issue date: January 2020

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 81527803, 81420108018, U1432114, 81550110258, 8161101589, 81650410654 and 31971292), National Key R&D Program of China (Nos. 2018YFC0115900 and 2018YFC0910601), Key Breakthrough Program of Chinese Academy of Sciences (No. KGZD-EW-T06), Zhejiang Science and Technology Project (No. 2019C03077), the Hundred Talents Program of Chinese Academy of Sciences (No. 2010-735), Youth Natural Science Fund Project of Zhejiang Province (No. LQ19H180004), Natural Science Fund Project of Ningbo City (No. 2018A610380), and Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province (No. 2019E10020). We acknowledge Ruifen Zou for help in animal experiments, and Ting Xue for help of Material characterization.

Return