Pancreatic cancer cell line in responsive hydrogel microcapsules for drug evaluation

Abstract

Drug therapies are the cornerstone of systemic treatment for pancreatic cancer patients. However, the relative outcome of drug evaluation is often hampered by the complex microenvironment of pancreatic cancer due to the lack of reasonable tumor models. Here, we proposed a novel platform that integrated pancreatic adenocarcinoma cells encapsulated into hydrogel microcapsules for three-dimensional (3D) tumor cultivation and antitumor agent evaluation. These hydrogel microcapsules contain alginate/poly (N-isopropyl acrylamide) (alginate/PNIPAM) shells and carboxymethyl cellulose cores, which are generated through the microfluidic electrospray technique. The microcapsules have the feature of rapid response to temperature, by which they can regulate the internal pressure environment. Besides, benefiting from good monodispersity, precise size control, and biocompatibility of these microcapsules, these wrapped tumor cells have the capacity for proliferating spontaneously and forming 3D tumors pheroids with good cell viability. We have demonstrated that pancreatic adenocarcinoma cells encapsulated in the composite microcapsules with different PNIPAM concentrations showed different drug sensitivity, which could be ascribed to the influence of external pressures environment. These results indicate that the tumor spheroids coated in these responsive microcapsules have great potential in the analysis of antitumor drug sensitivity.

Keywords

composite hydrogel / drug evaluation / microcapsule / microfluidics / pancreatic cancer

References

[1] H. Zhu, T. Li, Y. Du, M. Li, BMC Med. 2018, 16, 214.

[2] J. P. Neoptolemos, J. Kleeff, P. Michl, E. Costello, W. Greenhalf, D. H. Palmer, Nat. Rev. Gastroenterol. Hepatol. 2018, 15, 333.

[3] C. Springfeld, D. Jäger, M. W. Buchler, O. Strobel, T. Hackert, D. H. Palmer, J. P. Neoptolemos, Presse Med. 2019, 48, e159.

[4] a)Z. Zhang, Y. C. Chen, S. Urs, L. Chen, D. M. Simeone, E. Yoon, Small 2018, 14, e1703617. b)T. Mulholland, M. McAllister, S. Patek, D. Flint, M. Underwood, A. Sim, J. Edwards, M. Zagnoni, Sci. Rep. 2018, 8, 14672.

[5] a)M. Ligorio, S. Sil, J. Malagon-Lopez, L. T. Nieman, S. Misale, M. Di Pilato, R. Y. Ebright, M. N. Karabacak, A. S. Kulkarni, A. Liu, N. Vincent Jordan, J. W. Franses, J. Philipp, J. Kreuzer, N. Desai, K. S. Arora, M. Rajurkar, E. Horwitz, A. Neyaz, E. Tai, N. K. C. Magnus, K. D. Vo, C. N. Yashaswini, F. Marangoni, M. Boukhali, J. P. Fatherree, L. J. Damon, K. Xega, R. Desai, M. Choz, et al. F. Bersani, A. Langenbucher, V. Thapar, R. Morris, U. F. Wellner, O. Schilling, M. S. Lawrence, A. S. Liss, M. N. Rivera, V. Deshpande, C. H. Benes, S. Maheswaran, D. A. Haber, C. Fernandez-Del-Castillo, C. R. Ferrone, W. Haas, M. J. Aryee, D. T. Ting, Cell 2019, 178, 160. b)S. Raghavan, P. S. Winter, A. W. Navia, H. L. Williams, A. DenAdel, K. E. Lowder, J. Galvez-Reyes, R. L. Kalekar, N. Mulugeta, K. S. Kapner, M. S. Raghavan, A. A. Borah, N. Liu, S. A. Väyrynen, A. D. Costa, R. W. S. Ng, J. Wang, E. K. Hill, D. Y. Ragon, L. K. Brais, A. M. Jaeger, L. F. Spurr, Y. Y. Li, A. D. Cherniack, M. A. Booker, E. F. Cohen, M. Y. Tolstorukov, I. Wakiro, A. Rotem, B. E. Johnson, et al. J. M. McFarland, E. T. Sicinska, T. E. Jacks, R. J. Sullivan, G. I. Shapiro, T. E. Clancy, K. Perez, D. A. Rubinson, K. Ng, J. M. Cleary, L. Crawford, S. R. Manalis, J. A. Nowak, B. M. Wolpin, W. C. Hahn, A. J. Aguirre, A. K. Shalek, Cell 2021, 184, 6119. c)M. Paškevičiūtė, V. Petrikaitė, Drug Des. Dev. Ther. 2017, 11, 3273.

[6] a)M. V. Monteiro, V. M. Gaspar, L. Mendes, I. F. Duarte, J. F. Mano, Small Methods 2021, 5, e2001207. b)M. A. Heinrich, A. Mostafa, J. P. Morton, L. Hawinkels, J. Prakash, Adv. Drug. Deliv. Rev. 2021, 174, 265.

[7] a)C. R. Below, J. Kelly, A. Brown, J. D. Humphries, C. Hutton, J. Xu, B. Y. Lee, C. Cintas, X. Zhang, V. Hernandez-Gordillo, L. Stockdale, M. A. Goldsworthy, J. Geraghty, L. Foster, D. A. O’Reilly, B. Schedding, J. Askari, J. Burns, N. Hodson, D. L. Smith, C. Lally, G. Ashton, D. Knight, A. Mironov, A. Banyard, J. A. Eble, J. P. Morton, M. J. Humphries, L. G. Griffith, C. Jørgensen, Nat. Mater. 2021, 21, 110. b)M. Huber, C. U. Brehm, T. M. Gress, M. Buchholz, B. Alashkar Alhamwe, E. P. von Strandmann, E. P. Slater, J. W. Bartsch, C. Bauer, M. Lauth, Int. J. Mol. Sci. 2020, 21, 7307.

[8] T. Murakami, Y. Hiroshima, R. Matsuyama, Y. Homma, R. M. Hoffman, I. Endo, Ann. Gastroenterol. Surg. 2019, 3, 130.

[9] a)Z. Luo, J. Che, L. Sun, L. Yang, Y. Zu, H. Wang, Y. Zhao, Eng. Regen. 2021, 2, 257. b)Z. Zhang, Z. Chen, Y. Wang, J. Chi, Y. Wang, Y. Zhao, Small Methods 2019, 3, 1900519. c)H. Wang, Z. Zhao, Y. Liu, C. Shao, F. Bian, Y. Zhao, Sci.Adv. 2018, 4, eaat2816. d)H. Chen, Y. Zhao, J. Li, M. Guo, J. Wan, D. A. Weitz, H. A. Stone, Lab Chip 2011, 11, 2312. e)H. Wang, Y. Liu, Z. Chen, L. Sun, Y. Zhao, Sci. Adv. 2020, 6, eaay1438. f)Y. Yu, J. Guo, H. Zhang, X. Wang, C. Yang, Y. Zhao, Innovation 2022, 3, 100209. g)Y. Zhao, X. Zhao, X. Pei, J. Hu, W. Zhao, B. Chen, Z. Gu, Anal. Chim. Acta 2009, 633, 103. h)H. Wang, L. Cai, D. Zhang, L. Shang, Y. Zhao, Research 2021, 2021, 9829068. i)L. Qiu, B. Kong, T. Kong, H. Wang, Smart Med. 2023, 2, e20220010. j)B. Kong, C. Qi, H. Wang, T. Kong, Z. Liu, Smart Med. 2023, 2, e20220033. k)J. Hu, X. Zhao, Y. Zhao, J. Li, W. Xu, Z. Wen, M. Xu, Z. Gu, J. Mater. Chem. 2009, 19, 5730.

[10] a)L. Sun, L. Fan, F. Bian, G. Chen, Y. Wang, Y. Zhao, Research 2021, 2021, 9838490. b)M. Khanmohammadi, V. Zolfagharzadeh, Z. Bagher, H. Soltani, J. Ai, Biomed. Phys. Eng. Express 2020, 6, 015022. c)C. Zhao, Y. Yu, X. Zhang, X. Wu, J. Ren, Y. Zhao, Sci. Bull. 2019, 64, 1418. d)H. Wang, H. Zhang, Z. Xie, K. Chen, M. Ma, Y. Huang, M. Li, Z. Cai, P. Wang, H. Shen, Eng. Regen. 2021, 3, 407. e)L. Yang, Y. Liu, L. Sun, C. Zhao, G. Chen, Y. Zhao, Nano Micro Lett. 2021, 14, 4. f)H. Wang, H. Zhang, Z. Chen, Y. Zhao, Z. Gu, L. Shang, Prog.Mater. Sci. 2023, 135, 101091. g)Y. Hu, H. Zhang, H. Wei, H. Cheng, J. Cai, X. Chen, L. Xia, H. Wang, R. Chai, Eng. Regen. 2021, 3, 154.

[11] a)C. W. Wong, H. W. Han, Y. W. Tien, S. H. Hsu, Biomaterials 2019, 213, 119202. b)H. Lai, Y. Liu, G. Huang, Y. Chen, Y. Song, Y. Ma, P. Yue, Int. J. Biol. Macromol. 2021, 183, 2314. c)L. Yang, L. Sun, H. Zhang, F. Bian, Y. Zhao, ACS Nano 2021, 15, 20600. d)H. Wang, H. Zhang, B. Kong, P. Wang, H. Shen, Mater. Design 2023, 234, 112355. e)R. Huang, H. Zhang, L. Lv, Y. Zhang, J. Li, H. Wang, W. Gao, Mater. Design 2023, 234, 112336. f)J. Shan, X. Li, Z. Huang, B. Kong, H. Wang, L. Ren, Macromol. Biosci. 2023, 23, 2300006.

[12] a)M. A. Cooperstein, P. A. Nguyen, H. E. Canavan, Biointerphases 2017, 12, 02c401. b)M. A. Cooperstein, B. M. Bluestein, H. E. Canavan, Biointerphases 2014, 10, 019001.

[13] a)A. J. Rice, E. Cortes, D. Lachowski, B. C. H. Cheung, S. A. Karim, J. P. Morton, A. Del Río Hernández, Oncogenesis 2017, 6, e352. b)S. Safaei, R. Sajed, A. Shariftabrizi, S. Dorafshan, L. Saeednejad Zanjani, M. Dehghan Manshadi, Z. Madjd, R. Ghods, Cancer Cell Int. 2023, 23, 143.

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2023 The Authors. View published by Shanghai Fuji Technology Consulting Co., Ltd, authorized by Professional Community of Experimental Medicine, National Association of Health Industry and Enterprise Management (PCEM) and John Wiley & Sons Australia, Ltd.