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Research Article

Platelet membrane-coated C-TiO2 hollow nanospheres for combined sonodynamic and alkyl-radical cancer therapy

Weihong Guo4,§, Tao Wang2,§, Chunyu Huang1,5,§, Shipeng Ning6,§, Qinglong Guo2, Wei Zhang3, Huawei Yang6, Daoming Zhu4, Qinqin Huang1( ), Haisheng Qian3, Xianwen Wang3( )
Department of Molecular Pathology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China
Department of Orthopaedics, The Second Hospital of Anhui Medical University, Hefei 230601, China
School of Biomedical Engineering, Research and Engineering Center of Biomedical Materials, Anhui Medical University, Hefei 230032, China
Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China
Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning 530000, China

§ Weihong Guo, Tao Wang, Chunyu Huang, and Shipeng Ning contributed equally to this work.

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Graphical Abstract

Biomimetic C-TiO2/AIPH@PM, composed of 2,2′-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH)-loaded C-TiO2 hollow nanoshells (HNSs) as the inner cores and platelet membrane (PM) as the outer shells, was successfully prepared for synergistic sonodynamic therapy (SDT) and O2-independent alkyl-radical therapy.

Abstract

The therapeutic efficiency of sonodynamic therapy (SDT) mainly depends on the presence of oxygen (O2) to generate harmful reactive oxygen species (ROS); thus, the hypoxic tumor microenvironment significantly limits the efficacy of SDT. Therefore, the development of oxygen-independent free radical generators and associated combination therapy tactics can be a promising field to facilitate the anticancer capability of SDT. In this study, a biomimetic drug delivery system (C-TiO2/AIPH@PM) composed of an alkyl-radical generator (2,2′-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride, AIPH)-loaded C-TiO2 hollow nanoshells (HNSs) as the inner cores, and a platelet membrane (PM) as the outer shells is successfully prepared for synergistic SDT and oxygen-independent alkyl-radical therapy. The PM encapsulation can significantly prolong the blood circulation time of C-TiO2/AIPH@PM compared with C-TiO2/AIPH while enabling C-TiO2/AIPH@PM to achieve tumor targeting. C-TiO2/AIPH@PM can efficiently produce ROS and alkyl radicals, which can achieve a more thorough tumor eradication regardless of the normoxic or hypoxic conditions. Furthermore, the generation of these radicals improves the efficiency of SDT. In addition, nitrogen (N2) produced due to the decomposition of AIPH enhances the acoustic cavitation effect and lowers the cavitation threshold, thereby enhancing the penetration of C-TiO2/AIPH@PM at the tumor sites. Both in vitro and in vivo experiments demonstrate that C-TiO2/AIPH@PM possesses good biosafety, ultrasound imaging performance, and excellent anticancer efficacy. This study provides a new strategy to achieve oxygen-independent free radical production and enhance therapeutic efficacy by combining SDT and free radical therapy.

Keywords

C-TiO2sonodynamic therapyalkyl-radical therapycombination therapybiomimetic nanomaterials

Electronic Supplementary Material

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References

[1]

Meng, X. Q.; Li, D. D.; Chen, L.; He, H.; Wang, Q.; Hong, C. Y.; He, J. Y.; Gao, X. F.; Yang, Y. L.; Jiang, B. et al. High-performance self-cascade pyrite nanozymes for apoptosis-ferroptosis synergistic tumor therapy. ACS Nano 2021, 15, 5735–5751.
Crossref Google Scholar
[2]

Yan, J. Q.; Chen, J.; Zhang, N.; Yang, Y. D.; Zhu, W. W.; Li, L.; He, B. Mitochondria-targeted tetrahedral DNA nanostructures for doxorubicin delivery and enhancement of apoptosis. J. Mater. Chem. B 2020, 8, 492–503.
Crossref Google Scholar
[3]

Yan, J. Q.; Zhang, N.; Zhang, Z. Z.; Zhu, W. W.; Li, B.; Li, L.; Pu, Y. J.; He, B. Redox-responsive polyethyleneimine/tetrahedron DNA/doxorubicin nanocomplexes for deep cell/tissue penetration to overcome multidrug resistance. J. Control. Release 2021, 329, 36–49.
Crossref Google Scholar
[4]

Zhang, Y.; Zhang, X. Q.; Yang, H. C.; Yu, L.; Xu, Y. J.; Sharma, A.; Yin, P.; Li, X. Y.; Kim, J. S.; Sun, Y. Advanced biotechnology-assisted precise sonodynamic therapy. Chem. Soc. Rev. 2021, 50, 11227–11248.
Crossref Google Scholar
[5]

Wang, H.; Guo, J. X.; Lin, W.; Fu, Z.; Ji, X. R.; Yu, B.; Lu, M.; Cui, W. G.; Deng, L. F.; Engle, J. W. et al. Open-shell nanosensitizers for glutathione responsive cancer sonodynamic therapy. Adv. Mater. 2022, 34, 2110283.
Crossref Google Scholar
[6]

Zhu, D. M.; Chen, H.; Huang, C. Y.; Li, G. X.; Wang, X.; Jiang, W.; Fan, K. L. H2O2 self-producing single-atom nanozyme hydrogels as light-controlled oxidative stress amplifier for enhanced synergistic therapy by transforming “cold” tumors. Adv. Funct. Mater. 2022, 32, 2110268.
Crossref Google Scholar
[7]

Fan, Q.; He, Z. M.; Xiong, J. X.; Chao, J. Smart drug delivery systems based on DNA nanotechnology. ChemPlusChem 2022, 87, e202100548.
Crossref Google Scholar
[8]

Wang, X. W.; Zhong, X. Y.; Li, J. X.; Liu, Z.; Cheng, L. Inorganic nanomaterials with rapid clearance for biomedical applications. Chem. Soc. Rev. 2021, 50, 8669–8742.
Crossref Google Scholar
[9]

Zhang, R. F.; Chen, L.; Liang, Q.; Xi, J. Q.; Zhao, H. Q.; Jin, Y. L.; Gao, X. F.; Yan, X. Y.; Gao, L. Z.; Fan, K. L. Unveiling the active sites on ferrihydrite with apparent catalase-like activity for potentiating radiotherapy. Nano Today 2021, 41, 101317.
Crossref Google Scholar
[10]

Tang, G. H.; He, J. Y.; Liu, J. W.; Yan, X. Y.; Fan, K. L. Nanozyme for tumor therapy: Surface modification matters. Exploration 2021, 1, 75–89.
Crossref Google Scholar
[11]

Yang, N. L.; Gong, F.; Cheng, L.; Lei, H. L.; Li, W.; Sun, Z. B.; Ni, C. F.; Wang, Z. H.; Liu, Z. Biodegradable magnesium alloy with eddy thermal effect for effective and accurate magnetic hyperthermia ablation of tumors. Natl. Sci. Rev. 2021, 8, nwaa122.
Crossref Google Scholar
[12]

Xu, S. Y.; Shi, X. X.; Ren, E.; Zhang, J. Z.; Gao, X.; Mu, D.; Liu, C.; Liu, G. Genetically engineered nanohyaluronidase vesicles: A smart sonotheranostic platform for enhancing cargo penetration of solid tumors. Adv. Funct. Mater. 2022, 32, 2112989.
Crossref Google Scholar
[13]
Ju, Y. Y.; Shi, X. X.; Xu, S. Y.; Ma, X. H.; Wei, R. J.; Hou, H.; Chu, C. C.; Sun, D.; Liu, G.; Tan, Y. Z. Atomically precise water-soluble graphene quantum dot for cancer sonodynamic therapy. Adv. Sci., in press, https://doi.org/10.1002/advs.202105034.
[14]

Wang, M. F.; Hou, Z. Y.; Liu, S. N.; Liang, S.; Ding, B. B.; Zhao, Y. J.; Chang, M. Y.; Han, G.; Al Kheraif, A. A.; Lin, J. A multifunctional nanovaccine based on l-arginine-loaded black mesoporous titania: Ultrasound-triggered synergistic cancer sonodynamic therapy/gas therapy/immunotherapy with remarkably enhanced efficacy. Small 2021, 17, 2005728.
Crossref Google Scholar
[15]
Zhu, D. M.; Ling, R. Y.; Chen, H.; Lyu, M.; Qian, H. S.; Wu, K. L.; Li, G. X.; Wang, X. W. Biomimetic copper single-atom nanozyme system for self-enhanced nanocatalytic tumor therapy. Nano Res., in press, https://doi.org/10.1007/s12274-022-4359-6.
[16]

Zhu, D. M.; Zhang, T. F.; Li, Y.; Huang, C. Y.; Suo, M.; Xia, L. G.; Xu, Y. H.; Li, G. X.; Tang, B. Z. Tumor-derived exosomes co-delivering aggregation-induced emission luminogens and proton pump inhibitors for tumor glutamine starvation therapy and enhanced type-I photodynamic therapy. Biomaterials 2022, 283, 121462.
Crossref Google Scholar
[17]

Fan, K. L.; Xi, J. Q.; Fan, L.; Wang, P. X.; Zhu, C. H.; Tang, Y.; Xu, X. D.; Liang, M. M.; Jiang, B.; Yan, X. Y. et al. In vivo guiding nitrogen-doped carbon nanozyme for tumor catalytic therapy. Nat. Commun. 2018, 9, 1440.
Crossref Google Scholar
[18]

Pan, X. T.; Wang, W. W.; Huang, Z. J.; Liu, S.; Guo, J.; Zhang, F. R.; Yuan, H. J.; Li, X.; Liu, F. Y.; Liu, H. Y. MOF-derived double-layer hollow nanoparticles with oxygen generation ability for multimodal imaging-guided sonodynamic therapy. Angew. Chem. 2020, 132, 13659–13663.
Crossref Google Scholar
[19]

Pan, X. T.; Bai, L. X.; Wang, H.; Wu, Q. Y.; Wang, H. Y.; Liu, S.; Xu, B. L.; Shi, X. H.; Liu, H. Y. Metal-organic-framework-derived carbon nanostructure augmented sonodynamic cancer therapy. Adv. Mater. 2018, 30, 1800180.
Crossref Google Scholar
[20]

Wang, W. W.; Pan, X. T.; Yang, H. L.; Wang, H.; Wu, Q. Y.; Zheng, L. R.; Xu, B. L.; Wang, J. H.; Shi, X. H.; Bai, F. et al. Bioactive metal-organic frameworks with specific metal-nitrogen (M-N) active sites for efficient sonodynamic tumor therapy. ACS Nano 2021, 15, 20003–20012.
Crossref Google Scholar
[21]

Zhu, J. Y.; Ouyang, A.; Shen, Z. L.; Pan, Z. H.; Banerjee, S.; Zhang, Q. L.; Chen, Y. T.; Zhang, P. Y. Sonodynamic cancer therapy by novel iridium-gold nanoassemblies. Chin. Chem. Lett. 2022, 33, 1907–1912.
Crossref Google Scholar
[22]

Zhang, H. Y.; Pan, X. T.; Wu, Q. Y.; Guo, J.; Wang, C. H.; Liu, H. Y. Manganese carbonate nanoparticles-mediated mitochondrial dysfunction for enhanced sonodynamic therapy. Exploration 2021, 1, 20210010.
Crossref Google Scholar
[23]

Yue, W. W.; Chen, L.; Yu, L. D.; Zhou, B. G.; Yin, H. H.; Ren, W. W.; Liu, C.; Guo, L. H.; Zhang, Y. F.; Sun, L. P. et al. Checkpoint blockade and nanosonosensitizer-augmented noninvasive sonodynamic therapy combination reduces tumour growth and metastases in mice. Nat. Commun. 2019, 10, 2025.
Crossref Google Scholar
[24]

Guan, X.; Yin, H. H.; Xu, X. H.; Xu, G.; Zhang, Y.; Zhou, B. G.; Yue, W. W.; Liu, C.; Sun, L. P.; Xu, H. X. et al. Tumor metabolism-engineered composite nanoplatforms potentiate sonodynamic therapy via reshaping tumor microenvironment and facilitating electron–hole pairs’ separation. Adv. Funct. Mater. 2020, 30, 2000326.
Crossref Google Scholar
[25]

Yin, Y. F.; Jiang, X. W.; Sun, L. P.; Li, H. Y.; Su, C. X.; Zhang, Y.; Xu, G.; Li, X. L.; Zhao, C. K.; Chen, Y. et al. Continuous inertial cavitation evokes massive ROS for reinforcing sonodynamic therapy and immunogenic cell death against breast carcinoma. Nano Today 2021, 36, 101009.
Crossref Google Scholar
[26]

Wang, X. W.; Wang, X. Y.; Yue, Q. F.; Xu, H. Z.; Zhong, X. Y.; Sun, L. N.; Li, G. Q.; Gong, Y. H.; Yang, N. L.; Wang, Z. H. et al. Liquid exfoliation of TiN nanodots as novel sonosensitizers for photothermal-enhanced sonodynamic therapy against cancer. Nano Today 2021, 39, 101170.
Crossref Google Scholar
[27]

Sun, L. N.; Cao, Y.; Lu, Z. Z.; Ding, P.; Wang, Z. L.; Ma, F. S.; Wang, Z.; Pei, R. J. A hypoxia-irrelevant Fe-doped multivalent manganese oxide sonosensitizer via a vacancy engineering strategy for enhanced sonodynamic therapy. Nano Today 2022, 43, 101434.
Crossref Google Scholar
[28]

Wu, T. T.; Liu, Y.; Cao, Y.; Liu, Z. H. Engineering macrophage exosome disguised biodegradable nanoplatform for enhanced sonodynamic therapy of glioblastoma. Adv. Mater. 2022, 34, 2110364.
Crossref Google Scholar
[29]

Gong, C. C.; Zhao, J. M.; Meng, X. D.; Yang, Z.; Dong, H. F. Engineering Cu-CuFe2O4 nanoenzyme for hypoxia-relief and GSH-depletion enhanced chemodynamic/sonodynamic therapy. Chem. Eng. J. 2022, 435, 135083.
Crossref Google Scholar
[30]

Yang, K. K.; Yue, L. D.; Yu, G. C.; Rao, L.; Tian, R.; Wei, J. W.; Yang, Z. Q.; Sun, C.; Zhang, X. J.; Xu, M. Z. et al. A hypoxia responsive nanoassembly for tumor specific oxygenation and enhanced sonodynamic therapy. Biomaterials 2021, 275, 120822.
Crossref Google Scholar
[31]

Zhu, P.; Chen, Y.; Shi, J. L. Nanoenzyme-augmented cancer sonodynamic therapy by catalytic tumor oxygenation. ACS Nano 2018, 12, 3780–3795.
Crossref Google Scholar
[32]

Guo, Q. L.; Dai, X. L.; Yin, M. Y.; Cheng, H. W.; Qian, H. S.; Wang, H.; Zhu, D. M.; Wang, X. W. Nanosensitizers for sonodynamic therapy for glioblastoma multiforme: Current progress and future perspectives. Military Med. Res. 2022, 9, 26.
Crossref Google Scholar
[33]

Huang, D. Q.; Zhao, C.; Wen, B. J.; Fu, X.; Shang, L. R.; Kong, W. T.; Zhao, Y. J. Oxygen-carrying microfluidic microcapsules for enhancing chemo-sonodynamic therapy on patient-derived tumor organoid models. Chem. Eng. J. 2022, 435, 134871.
Crossref Google Scholar
[34]

Lin, X. H.; Qiu, Y.; Song, L.; Chen, S.; Chen, X. F.; Huang, G. M.; Song, J. B.; Chen, X. Y.; Yang, H. H. Ultrasound activation of liposomes for enhanced ultrasound imaging and synergistic gas and sonodynamic cancer therapy. Nanoscale Horiz. 2019, 4, 747–756.
Crossref Google Scholar
[35]

Sun, Y.; Cao, J.; Wang, X.; Zhang, C.; Luo, J. L.; Zeng, Y. Q.; Zhang, C.; Li, Q. Y.; Zhang, Y.; Xu, W. et al. Hypoxia-adapted sono-chemodynamic treatment of orthotopic pancreatic carcinoma using copper metal-organic frameworks loaded with an ultrasound-induced free radical initiator. ACS Appl. Mater. Interfaces 2021, 13, 38114–38126.
Crossref Google Scholar
[36]

Ye, J. M.; Fu, Q. R.; Liu, L. T.; Chen, L. L.; Zhang, X.; Li, Q. Q.; Li, Z.; Su, L. C.; Zhu, R.; Song, J. B. et al. Ultrasound-propelled Janus Au NR-mSiO2 nanomotor for NIR-II photoacoustic imaging guided sonodynamic-gas therapy of large tumors. Sci. China Chem. 2021, 64, 2218–2229.
Crossref Google Scholar
[37]

Zhang, C.; Xin, L.; Li, J.; Cao, J.; Sun, Y.; Wang, X.; Luo, J. L.; Zeng, Y. Q.; Li, Q. Y.; Zhang, Y. et al. Metal-organic framework (MOF)-based ultrasound-responsive dual-sonosensitizer nanoplatform for hypoxic cancer therapy. Adv. Healthcare Mater. 2022, 11, 2101946.
Crossref Google Scholar
[38]

Shen, S.; Zhu, C. L.; Huo, D.; Yang, M. X.; Xue, J. J.; Xia, Y. N. A hybrid nanomaterial for the controlled generation of free radicals and oxidative destruction of hypoxic cancer cells. Angew. Chem., Int. Ed. 2017, 56, 8801–8804.
Crossref Google Scholar
[39]

Huang, G. M.; Qiu, Y.; Yang, F. F.; Xie, J. G.; Chen, X.; Wang, L. L.; Yang, H. H. Magnetothermally triggered free-radical generation for deep-seated tumor treatment. Nano Lett. 2021, 21, 2926–2931.
Crossref Google Scholar
[40]

Zhang, Y.; Wang, Q.; Ji, Y. S.; Fan, L. Y.; Ding, B. B.; Lin, J.; Wang, L. L. Mitochondrial targeted melanin@mSiO2 yolk–shell nanostructures for NIR-Ⅱ-driven photo-thermal-dynamic/immunotherapy. Chem. Eng. J. 2022, 435, 134869.
Crossref Google Scholar
[41]

Li, Y. C.; Yu, H. L.; Ren, J. J.; Lu, G. J.; Cao, Y.; Xu, Z. G.; Kang, Y. J.; Xue, P. Acidic TME-responsive nano-Bi2Se3@MnCaP as a NIR-II-triggered free radical generator for hypoxia-irrelevant phototherapy with high specificity and immunogenicity. Small 2022, 18, 2104302.
Crossref Google Scholar
[42]

Cao, Y.; Wu, T. T.; Dai, W. H.; Dong, H. F.; Zhang, X. J. TiO2 nanosheets with the Au nanocrystal-decorated edge for mitochondria-targeting enhanced sonodynamic therapy. Chem. Mater. 2019, 31, 9105–9114.
Crossref Google Scholar
[43]

Liang, S.; Deng, X. R.; Xu, G. Y.; Xiao, X.; Wang, M. F.; Guo, X. S.; Ma, P. A.; Cheng, Z. Y.; Zhang, D.; Lin, J. A novel Pt-TiO2 heterostructure with oxygen-deficient layer as bilaterally enhanced sonosensitizer for synergistic chemo-sonodynamic cancer therapy. Adv. Funct. Mater. 2020, 30, 1908598.
Crossref Google Scholar
[44]

Wang, X. W.; Wang, X. Y.; Zhong, X. Y.; Li, G. Q.; Yang, Z. J.; Gong, Y. H.; Liu, Z.; Cheng, L. V-TiO2 nanospindles with regulating tumor microenvironment performance for enhanced sonodynamic cancer therapy. Appl. Phys. Rev. 2020, 7, 041411.
Crossref Google Scholar
[45]

Wang, X. W.; Zhong, X. Y.; Cheng, L. Titanium-based nanomaterials for cancer theranostics. Coord. Chem. Rev. 2021, 430, 213662.
Crossref Google Scholar
[46]

Geng, B. J.; Xu, S.; Li, P.; Li, X. K.; Fang, F. L.; Pan, D. Y.; Shen, L. X. Platinum crosslinked carbon dot@TiO2−x p–n junctions for relapse-free sonodynamic tumor eradication via high-yield ROS and GSH depletion. Small 2022, 18, 2103528.
Crossref Google Scholar
[47]

Han, X. X.; Huang, J.; Jing, X. X.; Yang, D. Y.; Lin, H.; Wang, Z. G.; Li, P.; Chen, Y. Oxygen-deficient black titania for synergistic/enhanced sonodynamic and photoinduced cancer therapy at near infrared-II biowindow. ACS Nano 2018, 12, 4545–4555.
Crossref Google Scholar
[48]

Wang, X. W.; Zhong, X. Y.; Bai, L. X.; Xu, J.; Gong, F.; Dong, Z. L.; Yang, Z. J.; Zeng, Z. J.; Liu, Z.; Cheng, L. Ultrafine titanium monoxide (TiO1+x) nanorods for enhanced sonodynamic therapy. J. Am. Chem. Soc. 2020, 142, 6527–6537.
Crossref Google Scholar
[49]

Jiang, Q.; Wang, K.; Zhang, X. Y.; Ouyang, B. S.; Liu, H. X.; Pang, Z. Q.; Yang, W. L. Platelet membrane-camouflaged magnetic nanoparticles for ferroptosis-enhanced cancer immunotherapy. Small 2020, 16, 2001704.
Crossref Google Scholar
[50]

Li, B. Z.; Chu, T. J.; Wei, J. Y.; Zhang, Y. L.; Qi, F. L.; Lu, Z. F.; Gao, C.; Zhang, T. J.; Jiang, E. S.; Xu, J. C. et al. Platelet-membrane-coated nanoparticles enable vascular disrupting agent combining anti-angiogenic drug for improved tumor vessel impairment. Nano Lett. 2021, 21, 2588–2595.
Crossref Google Scholar
Nano Research
Volume 16 Issue 1,
January 2023
Pages 782-791
DOI: 10.1007/s12274-022-4646-2
Cite this article:
Guo W, Wang T, Huang C, et al. Platelet membrane-coated C-TiO2 hollow nanospheres for combined sonodynamic and alkyl-radical cancer therapy. Nano Research, 2023, 16(1): 782-791. https://doi.org/10.1007/s12274-022-4646-2
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Received: 11 May 2022
Revised: 09 June 2022
Accepted: 09 June 2022
Published: 28 July 2022
© Tsinghua University Press 2022
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