Research and application of thermosensitive Pickering emulsion with X-ray and ultrasound dual-modal imaging functions for intra-arterial embolization treatment

Ling Li; Anran Guo; Haixia Sun; Yanbing Zhao; Qing Yao; Ling Zhang; Peng Shi; Hongan Tian; Min Zheng

doi:10.1016/j.jpha.2024.101133

Volume 15 Issue 4

May 2025

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Article Navigation > Journal of Pharmaceutical Analysis > 2025 > 15(4): 101133

Ling Li, Anran Guo, Haixia Sun, Yanbing Zhao, Qing Yao, Ling Zhang, Peng Shi, Hongan Tian, Min Zheng. Research and application of thermosensitive Pickering emulsion with X-ray and ultrasound dual-modal imaging functions for intra-arterial embolization treatment[J]. Journal of Pharmaceutical Analysis, 2025, 15(4): 101133. doi: 10.1016/j.jpha.2024.101133

Citation:

Ling Li, Anran Guo, Haixia Sun, Yanbing Zhao, Qing Yao, Ling Zhang, Peng Shi, Hongan Tian, Min Zheng. Research and application of thermosensitive Pickering emulsion with X-ray and ultrasound dual-modal imaging functions for intra-arterial embolization treatment[J]. Journal of Pharmaceutical Analysis, 2025, 15(4): 101133. doi: 10.1016/j.jpha.2024.101133

Citation:

Ling Li, Anran Guo, Haixia Sun, Yanbing Zhao, Qing Yao, Ling Zhang, Peng Shi, Hongan Tian, Min Zheng. Research and application of thermosensitive Pickering emulsion with X-ray and ultrasound dual-modal imaging functions for intra-arterial embolization treatment[J]. Journal of Pharmaceutical Analysis, 2025, 15(4): 101133. doi: 10.1016/j.jpha.2024.101133

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Research and application of thermosensitive Pickering emulsion with X-ray and ultrasound dual-modal imaging functions for intra-arterial embolization treatment

doi: 10.1016/j.jpha.2024.101133

Ling Li^a,b,
Anran Guo^c,
Haixia Sun^d,
Yanbing Zhao^a,
Qing Yao^e,
Ling Zhang^a,
Peng Shi^d,
Hongan Tian^{b
,
,},
Min Zheng^{a
,
,}

a. School of Biomedical Engineering and Imaging, Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei, 437100, China;
b. Department of Radiology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, Hubei, 437100, China;
c. School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei, 437100, China;
d. School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, 511442, China;
e. Hubei Key Laboratory of Diabetes and Angiopathy, Medicine Research Institute, Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei, 437100, China

Funds:

This work was supported by the Hubei Province Nature Science Foundation of China (Grant No.: 2023AFB1077), the National Natural Science Foundation of China (Grant No.: 82003308), the Doctoral Start-up Fund Project of Hubei University of Science and Technology, China (Grant No.: BK202118), the Innovation team and Medical research program of Hubei University of Science and Technology, China (Grant Nos.: 2023T10 and 2022YKY05), and the Hubei Province Key R&

D Plan Big Health Local Special Project, China (Grant No.: 2022BCE042).

Received Date: Apr. 10, 2024
Accepted Date: Oct. 22, 2024
Rev Recd Date: Oct. 06, 2024
Publish Date: Oct. 24, 2024

Abstract

Abstract

Transcatheter arterial embolization (TAE) is the mainstay for treating advanced hepatocellular carcinoma (HCC), and the performance of the embolization material is crucial in TAE. With the development of medical imaging and the birth of “X-ray-free” technologies, we designed a new dual-mode imaging material of dimethoxy tetraphenyl ethylene (DMTPE) via emulsification by mixing poly(N-isopropylacrylamide-co-acrylic acid) (PNA) with lipiodol and fluorocarbons, which was evaluated for temperature sensitivity, stability, and dual-mode visualization in vitro. Additionally, blood vessel casting embolization and renal artery imaging were assessed in healthy rabbits. In a rabbit model with a VX2 tumor, the effectiveness of TAE for treating HCC was examined, with an emphasis on evaluating long-term outcomes of embolization and its effects on tumor growth, necrosis, and proliferation through imaging techniques. In vitro experiments confirmed that the temperature-sensitive dual-oil-phase Pickering emulsion had good flow, stable contrast, and embolism when the oil-to-oil ratio and water-to-oil ratio were both 7:3 (v/v) and stabilized with 8% PNA. Similarly, in vivo, arterial embolization confirmed the excellent properties of DMTPE prepared at the abovementioned ratios. It was observed that DMTPE not only has an antitumor effect but can also achieve dual imaging using X-rays and ultrasound, making it a promising excellent vascular embolization material for TAE in tumor treatment.
- Dual-modal imaging,
- Temperature sensitivity,
- Pickering emulsion,
- Transcatheter arterial embolization

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References(61)

References

[1]	J.M. Llovet, T. De Baere, L. Kulik, et al., Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma, Nat. Rev. Gastroenterol. Hepatol. 18 (2021) 293-313.
[2]	J. Fu, H. Wang, Precision diagnosis and treatment of liver cancer in China, Cancer Lett. 412 (2018) 283-288.
[3]	A. Vogel, T. Meyer, G. Sapisochin, et al., Hepatocellular carcinoma, Lancet 400 (2022) 1345-1362.
[4]	R.A. Baum, S. Baum, Interventional radiology: A half century of innovation, Radiology 273 (2014) S75-S91.
[5]	P. He, E. Ren, B. Chen, et al., A super-stable homogeneous Lipiodol-hydrophilic chemodrug formulation for treatment of hepatocellular carcinoma, Theranostics 12 (2022) 1769-1782.
[6]	M. Kudo, O. Matsui, N. Izumi, et al., JSH consensus-based clinical practice guidelines for the management of hepatocellular carcinoma: 2014 update by the liver cancer study group of Japan, Liver Cancer 3 (2014) 458-468.
[7]	J. Hu, H. Albadawi, B.W. Chong, et al., Advances in biomaterials and technologies for vascular embolization, Adv. Mater. 31 (2019), e1901071.
[8]	B. Zhong, Z. Jin, J. Chen, et al., Role of transarterial chemoembolization in the treatment of hepatocellular carcinoma, J. Clin. Transl. Hepatol. 11 (2023) 480-489.
[9]	M. Reig, A. Forner, J. Rimola, et al., BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update, J. Hepatol. 76 (2022) 681-693.
[10]	P. Giunchedi, M. Maestri, E. Gavini, et al., Transarterial chemoembolization of hepatocellular carcinoma-Agents and drugs: An overview. Part 2, Expert Opin. Drug Deliv. 10 (2013) 799-810.
[11]	M. Chen, G. Shu, X. Lv, et al., HIF-2α-targeted interventional chemoembolization multifunctional microspheres for effective elimination of hepatocellular carcinoma, Biomaterials 284 (2022), 121512.
[12]	R. Duran, K. Sharma, M.R. Dreher, et al., A novel inherently radiopaque bead for transarterial embolization to treat liver cancer-A pre-clinical study, Theranostics 6 (2016) 28-39.
[13]	Q. Wang, K. Qian, S. Liu, et al., X-ray visible and uniform alginate microspheres loaded with in situ synthesized BaSO4 nanoparticles for in vivo transcatheter arterial embolization, Biomacromolecules 16 (2015) 1240-1246.
[14]	J. Zeng, L. Li, H. Zhang, et al., Radiopaque and uniform alginate microspheres loaded with tantalum nanoparticles for real-time imaging during transcatheter arterial embolization, Theranostics 8 (2018) 4591-4600.
[15]	G. Yang, L. Xu, Y. Chao, et al., Hollow MnO2 as a tumor-microenvironment-responsive biodegradable nano-platform for combination therapy favoring antitumor immune responses, Nat. Commun. 8 (2017), 902.
[16]	Y. Liang, H. Yu, G. Feng, et al., High-performance poly(lactic-co-glycolic acid)-magnetic microspheres prepared by rotating membrane emulsification for transcatheter arterial embolization and magnetic ablation in VX2 liver tumors, ACS Appl. Mater. Interfaces 9 (2017) 43478-43489.
[17]	J. Chen, T. Qian, H. Zhang, et al., Combining dynamic contrast enhanced magnetic resonance imaging and microvessel density to assess the angiogenesis after PEI in a rabbit VX2 liver tumor model, Magn. Reson. Imaging 34 (2016) 177-182.
[18]	S. Tang, C. Fu, L. Tan, et al., Imaging-guided synergetic therapy of orthotopic transplantation tumor by superselectively arterial administration of microwave-induced microcapsules, Biomaterials 133 (2017) 144-153.
[19]	R. Iezzi, M. Santoro, R. Marano, et al., Low-dose multidetector CT angiography in the evaluation of infrarenal aorta and peripheral arterial occlusive disease, Radiology 263 (2012) 287-298.
[20]	T.I. Kostelnik, C. Orvig, Radioactive main group and rare earth metals for imaging and therapy, Chem. Rev. 119 (2019) 902-956.
[21]	D. Kim, J.H. Lee, H. Moon, et al., Development and evaluation of an ultrasound-triggered microbubble combined transarterial chemoembolization (TACE) formulation on rabbit VX2 liver cancer model, Theranostics 11 (2021) 79-92.
[22]	S. Tehrani Fateh, L. Moradi, E. Kohan, et al., Comprehensive review on ultrasound-responsive theranostic nanomaterials: Mechanisms, structures and medical applications, Beilstein J. Nanotechnol. 12 (2021) 808-862.
[23]	A. Yildirim, N.T. Blum, A.P. Goodwin, Colloids, nanoparticles, and materials for imaging, delivery, ablation, and theranostics by focused ultrasound (FUS), Theranostics 9 (2019) 2572-2594.
[24]	M.W.N. Burns, R.F. Mattrey, J. Lux, Microbubbles cloaked with hydrogels as activatable ultrasound contrast agents, ACS Appl. Mater. Interfaces 12 (2020) 52298-52306.
[25]	D. Cui, M. Ding, Z. Wang, et al., 360° open-ended and navigated magnetic resonance-guided microwave ablation for hepatic tumors in risk areas, J. Cancer Res. Ther. 18 (2022) 1286-1291.
[26]	M.F. Meloni, G. Francica, J. Chiang, et al., Use of contrast-enhanced ultrasound in ablation therapy of HCC: Planning, guiding, and assessing treatment response, J. Ultrasound Med. 40 (2021) 879-894.
[27]	J. Wu, G. Ma, Recent studies of Pickering emulsions: Particles make the difference, Small 12 (2016) 4633-4648.
[28]	D.J. McClements, C.E. Gumus, Natural emulsifiers-Biosurfactants, phospholipids, biopolymers, and colloidal particles: Molecular and physicochemical basis of functional performance, Adv. Colloid Interface Sci. 234 (2016) 3-26.
[29]	L. Yao, Y. Wang, Y. He, et al., Pickering emulsions stabilized by conjugated zein-soybean polysaccharides nanoparticles: Fabrication, characterization and functional performance, Polymers (Basel) 15 (2023), 4474.
[30]	Z. Li, W. Xu, J. Yang, et al., A tumor microenvironments-adapted polypeptide hydrogel/nanogel composite boosts antitumor molecularly targeted inhibition and immunoactivation, Adv. Mater. 34 (2022), e2200449.
[31]	Y. Zhao, Z. Zhang, Z. Pan, et al., Advanced bioactive nanomaterials for biomedical applications, Exploration (Beijing) 1 (2021), 20210089.
[32]	H. Chen, H. Zhu, J. Hu, et al., Highly compressed assembly of deformable nanogels into nanoscale suprastructures and their application in nanomedicine, ACS Nano 5 (2011) 2671-2680.
[33]	H. Li, K. Qian, H. Zhang, et al., Pickering gel emulsion of lipiodol stabilized by hairy nanogels for intra-artery embolization antitumor therapy, Chem. Eng. J. 418 (2021), 129534.
[34]	W. Meng, H. Sun, T. Mu, et al., Chitosan-based Pickering emulsion: A comprehensive review on their stabilizers, bioavailability, applications and regulations, Carbohydr. Polym. 304 (2023), 120491.
[35]	N. Xia, X. Lu, Z. Zheng, et al., Study on preparation of acylated soy protein and stability of emulsion, J. Sci. Food Agric. 101 (2021) 4959-4968.
[36]	W. Xiong, W. Wang, Y. Wang, et al., Dual temperature/pH-sensitive drug delivery of poly(N-isopropylacrylamide-co-acrylic acid) nanogels conjugated with doxorubicin for potential application in tumor hyperthermia therapy, Colloids Surf. B Biointerfaces 84 (2011) 447-453.
[37]	H. Zhou, W. Xie, A. Guo, et al., Temperature sensitive nanogels for real-time imaging during transcatheter arterial embolization, Des. Monomers Polym. 26 (2023) 31-44.
[38]	W. Xie, H. Li, H. Yu, et al., A thermosensitive Pickering gel emulsion with a high oil-water ratio for long-term X-ray imaging and permanent embolization of arteries, Nanoscale 15 (2023) 1835-1848.
[39]	S. Capece, F. Domenici, F. Brasili, et al., Complex interfaces i Phys. 18 (2016) 8378-8388.
[40]	U. Goncin, L. Curiel, C.R. Geyer, et al., Aptamer-functionalized microbubbles targeted to P-selectin for ultrasound molecular imaging of murine bowel inflammation, Mol. Imaging Biol. 25 (2023) 283-293.
[41]	V. Pathak, K. Roemhild, S. Schipper, et al., Theranostic trigger-responsive carbon monoxide-generating microbubbles, Small 18 (2022), e2200924.
[42]	K.G. Brown, J. Li, R. Margolis, et al., Assessment of transarterial chemoembolization using super-resolution ultrasound imaging and a rat model of hepatocellular carcinoma, Ultrasound Med. Biol. 49 (2023) 1318-1326.
[43]	J. Rong, M. Liang, F. Xuan, et al., Alginate-calcium microsphere loaded with thrombin: A new composite biomaterial for hemostatic embolization, Int. J. Biol. Macromol. 75 (2015) 479-488.
[44]	S.I. Jeon, M.S. Kim, H.J. Kim, et al., Biodegradable poly(lactide-co-glycolide) microspheres encapsulating hydrophobic contrast agents for transarterial chemoembolization, J. Biomater. Sci. Polym. Ed. 33 (2022) 409-425.
[45]	K.H. Hillebrandt, H. Everwien, N. Haep, et al., Strategies based on organ decellularization and recellularization, Transpl. Int. 32 (2019) 571-585.
[46]	B.E. Uygun, A. Soto-Gutierrez, H. Yagi, et al., Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix, Nat. Med. 16 (2010) 814-820.
[47]	D.A. Taylor, S.M. Kren, K. Rhett, et al., Characterization of perfusion decellularized whole animal body, isolated organs, and multi-organ systems for tissue engineering applications, Physiol. Rep. 9 (2021), e14817.
[48]	A.D. Pospelov, O.M. Kutova, Y.M. Efremov, et al., Breast cancer cell type and biomechanical properties of decellularized mouse organs drives tumor cell colonization, Cells 12 (2023), 2030.
[49]	M. He, A. Callanan, K. Lagaras, et al., Optimization of SDS exposure on preservation of ECM characteristics in whole organ decellularization of rat kidneys, J. Biomed. Mater. Res. B Appl. Biomater. 105 (2017) 1352-1360.
[50]	H. Tang, C. Cao, G. Zhang, et al., Impact of particle size of multivesicular liposomes on the embolic and therapeutic effects in rabbit VX2 liver tumor, Drug Deliv. 30 (2023) 1-16.
[51]	H. Chen, C. Xie, Y. Li, et al., Evaluation of the safety and efficacy of transarterial sevelamer embolization in a rabbit liver cancer model: A challenge on the size rule for vascular occlusion, Front. Bioeng. Biotechnol. 10 (2022), 1058042.
[52]	H. Zhang, Y. Ren, H. Li, et al., Renal and hepatic artery embolization with Pickering gel emulsion of lipiodol in rabbit, BMC Cancer 22 (2022), 1300.
[53]	L. Li, Y. Cao, H. Zhang, et al., Temperature sensitive nanogel-stabilized Pickering emulsion of fluoroalkane for ultrasound guiding vascular embolization therapy, J. Nanobiotechnology 21 (2023), 413.
[54]	S. Bhattacharya, V.K. Parihar, B.G. Prajapati, Unveiling the therapeutic potential of cabozantinib-loaded poly D, L-lactic-co-glycolic acid and polysarcosine nanoparticles in inducing apoptosis and cytotoxicity in human HepG2 hepatocellular carcinoma cell lines and in vivo anti-tumor activity in SCID female mice, Front. Oncol. 13 (2023), 1125857.
[55]	M. Ghahremani-Nasab, N. Akbari-Gharalari, A. Rahmani Del Bakhshayesh, et al., Synergistic effect of chitosan-alginate composite hydrogel enriched with ascorbic acid and alpha-tocopherol under hypoxic conditions on the behavior of mesenchymal stem cells for wound healing, Stem Cell Res. Ther. 14 (2023), 326.
[56]	R. Sobreiro-Almeida, M. Gomez-Florit, R. Quinteira, et al., Decellularized kidney extracellular matrix bioinks recapitulate renal 3D microenvironment in vitro, Biofabrication 13 (2021), 045006.
[57]	X. Gao, Z. Chen, Z. Chen, et al., Visualization and evaluation of chemoembolization on a 3D decellularized organ scaffold, ACS Biomater. Sci. Eng. 7 (2021) 5642-5653.
[58]	L. Li, Y. Liu, H. Li, et al., Rational design of temperature-sensitive blood-vessel-embolic nanogels for improving hypoxic tumor microenvironment after transcatheter arterial embolization, Theranostics 8 (2018) 6291-6306.
[59]	Q. Zhao, L. Zhang, Q. He, et al., Targeting TRMT5 suppresses hepatocellular carcinoma progression via inhibiting the HIF-1α pathways, J. Zhejiang Univ. Sci. B 24 (2023) 50-63.
[60]	A.K. Kai, L.K. Chan, R.C. Lo, et al., Down-regulation of TIMP2 by HIF-1α/miR-210/HIF-3α regulatory feedback circuit enhances cancer metastasis in hepatocellular carcinoma, Hepatology 64 (2016) 473-487.
[61]	A. Longchamp, T. Mirabella, A. Arduini, et al., Amino acid restriction triggers angiogenesis via GCN2/ATF4 regulation of VEGF and H₂S production, Cell 173 (2018),117-129.e14.