Protein-Based Artificial Nanosystems in Cancer Therapy
Nan Zhang
School of Natural and Applied Sciences, Northwestern Polytechnical University, Xi'an, 710072 P. R. China
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore, 637371 Singapore
Search for more papers by this authorKun Mei
School of Natural and Applied Sciences, Northwestern Polytechnical University, Xi'an, 710072 P. R. China
Search for more papers by this authorPing Guan
School of Natural and Applied Sciences, Northwestern Polytechnical University, Xi'an, 710072 P. R. China
Search for more papers by this authorCorresponding Author
Xiaoling Hu
School of Natural and Applied Sciences, Northwestern Polytechnical University, Xi'an, 710072 P. R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Yanli Zhao
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore, 637371 Singapore
School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798 Singapore
E-mail: [email protected]; [email protected]
Search for more papers by this authorNan Zhang
School of Natural and Applied Sciences, Northwestern Polytechnical University, Xi'an, 710072 P. R. China
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore, 637371 Singapore
Search for more papers by this authorKun Mei
School of Natural and Applied Sciences, Northwestern Polytechnical University, Xi'an, 710072 P. R. China
Search for more papers by this authorPing Guan
School of Natural and Applied Sciences, Northwestern Polytechnical University, Xi'an, 710072 P. R. China
Search for more papers by this authorCorresponding Author
Xiaoling Hu
School of Natural and Applied Sciences, Northwestern Polytechnical University, Xi'an, 710072 P. R. China
E-mail: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Yanli Zhao
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore, 637371 Singapore
School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798 Singapore
E-mail: [email protected]; [email protected]
Search for more papers by this authorAbstract
Proteins, like actors, play different roles in specific applications. In the past decade, significant achievements have been made in protein-engineered biomedicine for cancer therapy. Certain proteins such as human serum albumin, working as carriers for drug/photosensitizer delivery, have entered clinical use due to their long half-life, biocompatibility, biodegradability, and inherent nonimmunogenicity. Proteins with catalytic abilities are promising as adjuvant agents for other therapeutic modalities or as anticancer drugs themselves. These catalytic proteins are usually defined as enzymes with high biological activity and substrate specificity. However, clinical applications of these kinds of proteins remain rare due to protease-induced denaturation and weak cellular permeability. Based on the characteristics of different proteins, tailor-made protein-based nanosystems could make up for their individual deficiencies. Therefore, elaborately designed protein-based nanosystems, where proteins serve as drug carriers, adjuvant agents, or therapeutic drugs to make full use of their intrinsic advantages in cancer therapy, are reviewed. Up-to-date progress on research in the field of protein-based nanomedicine is provided.
Conflict of Interest
The authors declare no conflict of interest.
References
- 1a) G. Walsh, Nat. Biotechnol. 2014, 32, 992; b) A. M. Scott, J. D. Wolchok, L. J. Old, Nat. Rev. Cancer 2012, 12, 278.
- 2a) B. Leader, Q. J. Baca, D. E. Golan, Nat. Rev. Drug Discovery 2008, 7, 21; b) G. Walsh, Nat. Biotechnol. 2010, 28, 917; c) Y. Luo, Y. Song, M. Wang, T. Jian, S. Ding, P. Mu, Z. Liao, Q. Shi, X. Cai, H. Jin, Small 2019, 15, 1902485.
- 3M. Yan, J. Du, Z. Gu, M. Liang, Y. Hu, W. Zhang, S. Priceman, L. Wu, Z. H. Zhou, Z. Liu, T. Segura, Y. Tang, Y. Lu, Nat. Nanotechnol. 2010, 5, 48.
- 4E. N. Hoogenboezem, C. L. Duvall, Adv. Drug Delivery Rev. 2018, 130, 73.
- 5D. Sleep, J. Cameron, L. R. Evans, Biochim. Biophys. Acta, Gen. Subj. 2013, 1830, 5526.
- 6a) U. Kragh-Hansen, Pharmacol. Rev. 1981, 33, 17; b) S. Curry, H. Mandelkow, P. Brick, N. Franks, Nat. Struct. Biol. 1998, 5, 827.
- 7G. Yang, H. Gong, T. Liu, X. Sun, L. Cheng, Z. Liu, Biomaterials 2015, 60, 62.
- 8a) Z. Yang, Q. Chen, J. Chen, Z. Dong, R. Zhang, J. Liu, Z. Liu, Small 2018, 14, 1803262; b) Q. Chen, L. Feng, J. Liu, W. Zhu, Z. Dong, Y. Wu, Z. Liu, Adv. Mater. 2016, 28, 7129; c) S. Ruan, X. Cao, X. Cun, G. Hu, Y. Zhou, Y. Zhang, L. Lu, Q. He, H. Gao, Biomaterials 2015, 60, 100; d) K. Huang, H. Ma, J. Liu, S. Huo, A. Kumar, T. Wei, X. Zhang, S. Jin, Y. Gan, P. C. Wang, S. He, X. Zhang, X.-J. Liang, ACS Nano 2012, 6, 4483; e) S. Ruan, Q. He, H. Gao, Nanoscale 2015, 7, 9487.
- 9a) Z. Sheng, D. Hu, M. Zheng, P. Zhao, H. Liu, D. Gao, P. Gong, G. Gao, P. Zhang, Y. Ma, L. Cai, ACS Nano 2014, 8, 12310; b) Y. Peng, Z. Zhao, T. Liu, X. Li, X. Hu, X. Wei, X. Zhang, W. Tan, Angew. Chem., Int. Ed. 2017, 56, 10845; c) Q. Chen, J. Chen, C. Liang, L. Feng, Z. Dong, X. Song, G. Song, Z. Liu, J. Controlled Release 2017, 263, 79.
- 10Y. Hu, D. Chen, S. Park, T. Emrick, T. P. Russell, Adv. Mater. 2010, 22, 2583.
- 11L. Li, C. J. Fang, J. C. Ryan, E. C. Niemi, J. A. Lebrón, P. J. Björkman, H. Arase, F. M. Torti, S. V. Torti, M. C. Nakamura, W. E. Seaman, Proc. Natl. Acad. Sci. USA 2010, 107, 3505.
- 12a) P. Huang, P. Rong, A. Jin, X. Yan, M. G. Zhang, J. Lin, H. Hu, Z. Wang, X. Yue, W. Li, G. Niu, W. Zeng, W. Wang, K. Zhou, X. Chen, Adv. Mater. 2014, 26, 6401; b) Z. Zhen, W. Tang, C. Guo, H. Chen, X. Lin, G. Liu, B. Fei, X. Chen, B. Xu, J. Xie, ACS Nano 2013, 7, 6988; c) G. Jutz, P. van Rijn, B. Santos Miranda, A. Böker, Chem. Rev. 2015, 115, 1653; d) A. A. Alkhateeb, J. R. Connor, Biochim. Biophys. Acta Rev. Cancer 2013, 1836, 245; e) Z. Wang, P. Huang, O. Jacobson, Z. Wang, Y. Liu, L. Lin, J. Lin, N. Lu, H. Zhang, R. Tian, G. Niu, G. Liu, X. Chen, ACS Nano 2016, 10, 3453.
- 13a) Y. Lu, W. Sun, Z. Gu, J. Controlled Release 2014, 194, 1; b) J. E. Gagner, W. Kim, E. L. Chaikof, Acta Biomater. 2014, 10, 1542; c) R. Vaishya, V. Khurana, S. Patel, A. K. Mitra, Expert Opin. Drug Delivery 2015, 12, 415; d) C. Wang, Y. Ye, Q. Hu, A. Bellotti, Z. Gu, Adv. Mater. 2017, 29, 1606036.
- 14H. Wang, Y. Chao, J. Liu, W. Zhu, G. Wang, L. Xu, Z. Liu, Biomaterials 2018, 181, 310.
- 15H. Gong, Y. Chao, J. Xiang, X. Han, G. Song, L. Feng, J. Liu, G. Yang, Q. Chen, Z. Liu, Nano Lett. 2016, 16, 2512.
- 16a) X. Zhang, K. Zhang, R. Haag, Biomater. Sci. 2015, 3, 1487; b) E. M. Pelegri-O'Day, E.-W. Lin, H. D. Maynard, J. Am. Chem. Soc. 2014, 136, 14323.
- 17a) X. Song, J. Xu, C. Liang, Y. Chao, Q. Jin, C. Wang, M. Chen, Z. Liu, Nano Lett. 2018, 18, 6360; b) H. Chen, J. Tian, W. He, Z. Guo, J. Am. Chem. Soc. 2015, 137, 1539; c) D. Sueyoshi, Y. Anraku, T. Komatsu, Y. Urano, K. Kataoka, Biomacromolecules 2017, 18, 1189; d) Y. Anraku, A. Kishimura, M. Kamiya, S. Tanaka, T. Nomoto, K. Toh, Y. Matsumoto, S. Fukushima, D. Sueyoshi, M. R. Kano, Y. Urano, N. Nishiyama, K. Kataoka, Angew. Chem., Int. Ed. 2016, 55, 560; e) J. Li, Y. Li, Y. Wang, W. Ke, W. Chen, W. Wang, Z. Ge, Nano Lett. 2017, 17, 6983.
- 18a) I. Ortac, D. Simberg, Y.-s. Yeh, J. Yang, B. Messmer, W. C. Trogler, R. Y. Tsien, S. Esener, Nano Lett. 2014, 14, 3023; b) Y. Zhang, T.-T. Shen, A. M. Kirillov, W.-S. Liu, Y. Tang, Chem. Commun. 2016, 52, 7939; c) G. Shim, M.-G. Kim, J. Y. Park, Y.-K. Oh, Adv. Drug Delivery Rev. 2016, 105, 205; d) A. Castro Nava, M. Cojoc, C. Peitzsch, G. Cirillo, I. Kurth, S. Fuessel, K. Erdmann, D. Kunhardt, O. Vittorio, S. Hampel, A. Dubrovska, Int. J. Cancer 2015, 137, 2492; e) J. Y. Lee, J. S. Kim, J. C. Park, Y. S. Nam, Wiley Interdiscip. Rev.: Nanomed. Nanobiotechnol. 2016, 8, 178; f) S. Ding, Z. Li, Y. Cheng, C. Du, J. Gao, Y.-W. Zhang, N. Zhang, Z. Li, N. Chang, X. Hu, Nanotechnology 2018, 29, 375604; g) S. Ding, Z. Lyu, X. Niu, Y. Zhou, D. Liu, M. Falahati, D. Du, Y. Lin, Biosens. Bioelectron. 2019, 149, 111830.
- 19J. H. Ko, H. D. Maynard, Chem. Soc. Rev. 2018, 47, 8998.
- 20a) W. Chen, M. Zheng, F. Meng, R. Cheng, C. Deng, J. Feijen, Z. Zhong, Biomacromolecules 2013, 14, 1214; b) D. Li, C. F. van Nostrum, E. Mastrobattista, T. Vermonden, W. E. Hennink, J. Controlled Release 2017, 259, 16.
- 21a) Z. Gu, M. Yan, B. Hu, K.-I. Joo, A. Biswas, Y. Huang, Y. Lu, P. Wang, Y. Tang, Nano Lett. 2009, 9, 4533; b) W. Zhao, J. Hu, W. Gao, ACS Appl. Mater. Interfaces 2017, 9, 23528; c) C. Wang, Y. Ye, G. M. Hochu, H. Sadeghifar, Z. Gu, Nano Lett. 2016, 16, 2334; d) M. Zhao, A. Biswas, B. Hu, K.-I. Joo, P. Wang, Z. Gu, Y. Tang, Biomaterials 2011, 32, 5223.
- 22a) Z. Liu, X. Chen, Chem. Soc. Rev. 2016, 45, 1432; b) X. Liu, C. Wang, Z. Liu, Adv. Healthcare Mater. 2018, 7, 1800913; c) L.-H. Fu, C. Qi, J. Lin, P. Huang, Chem. Soc. Rev. 2018, 47, 6454; d) D. Jiang, D. Ni, Z. T. Rosenkrans, P. Huang, X. Yan, W. Cai, Chem. Soc. Rev. 2019, 48, 3683; e) L. Cheng, L. Yang, F. Meng, Z. Zhong, Adv. Healthcare Mater. 2018, 7, 1800685; f) J. Lv, Q. Fan, H. Wang, Y. Cheng, Biomaterials 2019, 218, 119358.
- 23Y. Hu, D. Samanta, S. S. Parelkar, S. W. Hong, Q. Wang, T. P. Russell, T. Emrick, Adv. Funct. Mater. 2010, 20, 3603.
- 24a) E. Falvo, E. Tremante, R. Fraioli, C. Leonetti, C. Zamparelli, A. Boffi, V. Morea, P. Ceci, P. Giacomini, Nanoscale 2013, 5, 12278; b) X. Lin, J. Xie, L. Zhu, S. Lee, G. Niu, Y. Ma, K. Kim, X. Chen, Angew. Chem., Int. Ed. 2011, 50, 1569; c) Y. J. Kang, H. J. Yang, S. Jeon, Y.-S. Kang, Y. Do, S. Y. Hong, S. Kang, Macromol. Biosci. 2014, 14, 619.
- 25a) D. He, J. Marles-Wright, New Biotechnol. 2015, 32, 651; b) I. Yamashita, K. Iwahori, S. Kumagai, Biochim. Biophys. Acta, Gen. Subj. 2010, 1800, 846.
- 26Z. Wang, Y. Dai, Z. Wang, O. Jacobson, F. Zhang, B. C. Yung, P. Zhang, H. Gao, G. Niu, G. Liu, X. Chen, Nanoscale 2018, 10, 1135.
- 27a) P. Arosio, R. Ingrassia, P. Cavadini, Biochim. Biophys. Acta, Gen. Subj. 2009, 1790, 589; b) M. Bellini, S. Mazzucchelli, E. Galbiati, S. Sommaruga, L. Fiandra, M. Truffi, M. A. Rizzuto, M. Colombo, P. Tortora, F. Corsi, D. Prosperi, J. Controlled Release 2014, 196, 184; c) M. Kim, Y. Rho, K. S. Jin, B. Ahn, S. Jung, H. Kim, M. Ree, Biomacromolecules 2011, 12, 1629.
- 28N. Surguladze, S. Patton, A. Cozzi, M. G. Fried, J. R. Connor, Biochem. J. 2005, 388, 731.
- 29Z. Zhen, W. Tang, H. Chen, X. Lin, T. Todd, G. Wang, T. Cowger, X. Chen, J. Xie, ACS Nano 2013, 7, 4830.
- 30a) X. Jiang, C. Sun, Y. Guo, G. Nie, L. Xu, Biosens. Bioelectron. 2015, 64, 165; b) B. Hennequin, L. Turyanska, T. Ben, A. M. Beltrán, S. I. Molina, M. Li, S. Mann, A. Patanè, N. R. Thomas, Adv. Mater. 2008, 20, 3592.
- 31a) J. Wu, X. Wang, Q. Wang, Z. Lou, S. Li, Y. Zhu, L. Qin, H. Wei, Chem. Soc. Rev. 2019, 48, 1004; b) W. Chen, K. Zeng, H. Liu, J. Ouyang, L. Wang, Y. Liu, H. Wang, L. Deng, Y.-N. Liu, Adv. Funct. Mater. 2017, 27, 1605795; c) X. Jia, X. Cai, Y. Chen, S. Wang, H. Xu, K. Zhang, M. Ma, H. Wu, J. Shi, H. Chen, ACS Appl. Mater. Interfaces 2015, 7, 4579.
- 32W. Zhang, Y. Zhang, Y. Chen, S. Li, N. Gu, S. Hu, Y. Sun, X. Chen, Q. Li, J. Nanosci. Nanotechnol. 2013, 13, 60.
- 33P. van Rijn, N. C. Mougin, D. Franke, H. Park, A. Böker, Chem. Commun. 2011, 47, 8376.
- 34a) S. Kang, P. A. Suci, C. C. Broomell, K. Iwahori, M. Kobayashi, I. Yamashita, M. Young, T. Douglas, Nano Lett. 2009, 9, 2360; b) P. A. Suci, S. Kang, M. Young, T. Douglas, J. Am. Chem. Soc. 2009, 131, 9164.
- 35a) Y. Wang, T. Yang, H. Ke, A. Zhu, Y. Wang, J. Wang, J. Shen, G. Liu, C. Chen, Y. Zhao, H. Chen, Adv. Mater. 2015, 27, 3874; b) Z. Yang, S. Luo, Y. Zeng, C. Shi, R. Li, ACS Appl. Mater. Interfaces 2017, 9, 6839; c) J. Zhang, G. Hao, C. Yao, J. Yu, J. Wang, W. Yang, C. Hu, B. Zhang, ACS Appl. Mater. Interfaces 2016, 8, 16612.
- 36C. Xu, Z. Teng, Y. Zhang, L. Yuwen, Q. Zhang, X. Su, M. Dang, Y. Tian, J. Tao, L. Bao, B. Yang, G. Lu, J. Zhu, Adv. Funct. Mater. 2018, 28, 1804081.
- 37H. Ren, J. Liu, F. Su, S. Ge, A. Yuan, W. Dai, J. Wu, Y. Hu, ACS Appl. Mater. Interfaces 2017, 9, 3463.
- 38Z. Zhou, Y. Liu, M. Zhang, C. Li, R. Yang, J. Li, C. Qian, M. Sun, Adv. Funct. Mater. 2019, 29, 1904144.
- 39G. Yang, S. Z. F. Phua, W. Q. Lim, R. Zhang, L. Feng, G. Liu, H. Wu, A. K. Bindra, D. Jana, Z. Liu, Y. Zhao, Adv. Mater. 2019, 31, 1901513.
- 40a) W. Z. Yuan, P. Lu, S. Chen, J. W. Y. Lam, Z. Wang, Y. Liu, H. S. Kwok, Y. Ma, B. Z. Tang, Adv. Mater. 2010, 22, 2159; b) M. Li, Y. Gao, Y. Yuan, Y. Wu, Z. Song, B. Z. Tang, B. Liu, Q. C. Zheng, ACS Nano 2017, 11, 3922.
- 41Y. M. Woo, Y. Shin, E. J. Lee, S. Lee, S. H. Jeong, H. K. Kong, E. Y. Park, H. K. Kim, J. Han, M. Chang, J.-H. Park, PLoS One 2015, 10, e0132285.
- 42S. L. Kuan, B. Stöckle, J. Reichenwallner, D. Y. W. Ng, Y. Wu, M. Doroshenko, K. Koynov, D. Hinderberger, K. Müllen, T. Weil, Biomacromolecules 2013, 14, 367.
- 43a) L. Palmerston Mendes, J. Pan, P. V. Torchilin, Molecules 2017, 22, 1401; b) Y. Dong, T. Yu, L. Ding, E. Laurini, Y. Huang, M. Zhang, Y. Weng, S. Lin, P. Chen, D. Marson, Y. Jiang, S. Giorgio, S. Pricl, X. Liu, P. Rocchi, L. Peng, J. Am. Chem. Soc. 2018, 140, 16264; c) T. Wei, C. Chen, J. Liu, C. Liu, P. Posocco, X. Liu, Q. Cheng, S. Huo, Z. Liang, M. Fermeglia, S. Pricl, X.-J. Liang, P. Rocchi, L. Peng, Proc. Natl. Acad. Sci. USA 2015, 112, 2978.
- 44G. Han, J.-T. Wang, X. Ji, L. Liu, H. Zhao, Bioconjugate Chem. 2017, 28, 636.
- 45T. Lin, P. Zhao, Y. Jiang, Y. Tang, H. Jin, Z. Pan, H. He, V. C. Yang, Y. Huang, ACS Nano 2016, 10, 9999.
- 46C. Saraiva, C. Praça, R. Ferreira, T. Santos, L. Ferreira, L. Bernardino, J. Controlled Release 2016, 235, 34.
- 47W. J. Geldenhuys, A. S. Mohammad, C. E. Adkins, P. R. Lockman, Ther. Delivery 2015, 6, 961.
- 48a) R. K. Mittapalli, V. K. Manda, C. E. Adkins, W. J. Geldenhuys, P. R. Lockman, Ther. Delivery 2010, 1, 775; b) A. M. Merlot, D. S. Kalinowski, D. R. Richardson, Front. Physiol. 2014, 5, 299.
- 49P. Zhang, H. Huang, S. Banerjee, G. J. Clarkson, C. Ge, C. Imberti, P. J. Sadler, Angew. Chem., Int. Ed. 2019, 58, 2350.
- 50C. Jin, H. Zhang, J. Zou, Y. Liu, L. Zhang, F. Li, R. Wang, W. Xuan, M. Ye, W. Tan, Angew. Chem., Int. Ed. 2018, 57, 8994.
- 51a) Y. Lou, P. C. McDonald, A. Oloumi, S. Chia, C. Ostlund, A. Ahmadi, A. Kyle, U. auf dem Keller, S. Leung, D. Huntsman, B. Clarke, B. W. Sutherland, D. Waterhouse, M. Bally, C. Roskelley, C. M. Overall, A. Minchinton, F. Pacchiano, F. Carta, A. Scozzafava, N. Touisni, J.-Y. Winum, C. T. Supuran, S. Dedhar, Cancer Res. 2011, 71, 3364; b) R. K. Jain, Cancer Cell 2014, 26, 605.
- 52a) P. Agostinis, K. Berg, K. A. Cengel, T. H. Foster, A. W. Girotti, S. O. Gollnick, S. M. Hahn, M. R. Hamblin, A. Juzeniene, D. Kessel, M. Korbelik, J. Moan, P. Mroz, D. Nowis, J. Piette, B. C. Wilson, J. Golab, Ca-Cancer J. Clin. 2011, 61, 250; b) N. M. Idris, M. K. Gnanasammandhan, J. Zhang, P. C. Ho, R. Mahendran, Y. Zhang, Nat. Med. 2012, 18, 1580; c) B. Tian, C. Wang, S. Zhang, L. Feng, Z. Liu, ACS Nano 2011, 5, 7000.
- 53a) R. Baskar, K. A. Lee, R. Yeo, K.-W. Yeoh, Int. J. Med. Sci. 2012, 9, 193; b) X.-D. Zhang, D. Wu, X. Shen, J. Chen, Y.-M. Sun, P.-X. Liu, X.-J. Liang, Biomaterials 2012, 33, 6408; c) G. Le Duc, I. Miladi, C. Alric, P. Mowat, E. Bräuer-Krisch, A. Bouchet, E. Khalil, C. Billotey, M. Janier, F. Lux, T. Epicier, P. Perriat, S. Roux, O. Tillement, ACS Nano 2011, 5, 9566.
- 54a) M. Gao, C. Liang, X. Song, Q. Chen, Q. Jin, C. Wang, Z. Liu, Adv. Mater. 2017, 29, 1701429; b) G. Song, C. Liang, X. Yi, Q. Zhao, L. Cheng, K. Yang, Z. Liu, Adv. Mater. 2016, 28, 2716; c) Z. Luo, M. Zheng, P. Zhao, Z. Chen, F. Siu, P. Gong, G. Gao, Z. Sheng, C. Zheng, Y. Ma, L. Cai, Sci. Rep. 2016, 6, 23393; d) W. Tang, Z. Zhen, M. Wang, H. Wang, Y.-J. Chuang, W. Zhang, G. D. Wang, T. Todd, T. Cowger, H. Chen, L. Liu, Z. Li, J. Xie, Adv. Funct. Mater. 2016, 26, 1757; e) F. B. Jensen, J. Exp. Biol. 2009, 212, 3387.
- 55a) M. López-Lázaro, Cancer Lett. 2007, 252, 1; b) A. R. Lippert, G. C. Van de Bittner, C. J. Chang, Acc. Chem. Res. 2011, 44, 793.
- 56a) J. Kim, H. R. Cho, H. Jeon, D. Kim, C. Song, N. Lee, S. H. Choi, T. Hyeon, J. Am. Chem. Soc. 2017, 139, 10992; b) W. Zhu, Z. Dong, T. Fu, J. Liu, Q. Chen, Y. Li, R. Zhu, L. Xu, Z. Liu, Adv. Funct. Mater. 2016, 26, 5490.
- 57C. Glorieux, B. Calderon Pedro, Biol. Chem. 2017, 398, 1095.
- 58R. Zhang, X. Song, C. Liang, X. Yi, G. Song, Y. Chao, Y. Yang, K. Yang, L. Feng, Z. Liu, Biomaterials 2017, 138, 13.
- 59M. Qiu, Z. Zhang, Y. Wei, H. Sun, F. Meng, C. Deng, Z. Zhong, Chem. Mater. 2018, 30, 6831.
- 60P. Yao, Y. Zhang, H. Meng, H. Sun, Z. Zhong, Biomacromolecules 2019, 20, 184.
- 61W. Yang, Y. Wei, L. Yang, J. Zhang, Z. Zhong, G. Storm, F. Meng, J. Controlled Release 2018, 290, 141.
- 62W. Yang, Y. Xia, Y. Zou, F. Meng, J. Zhang, Z. Zhong, Chem. Mater. 2017, 29, 8757.
- 63G. Liu, S. Ma, S. Li, R. Cheng, F. Meng, H. Liu, Z. Zhong, Biomaterials 2010, 31, 7575.
- 64a) Y. Jiang, W. Yang, J. Zhang, F. Meng, Z. Zhong, Adv. Mater. 2018, 30, 1800316; b) Y. Jiang, J. Zhang, F. Meng, Z. Zhong, ACS Nano 2018, 12, 11070.
- 65S. Z. F. Phua, G. Yang, W. Q. Lim, A. Verma, H. Chen, T. Thanabalu, Y. L. Zhao, ACS Nano 2019, 13, 4742.
- 66Q. Chen, J. Chen, Z. Yang, J. Xu, L. Xu, C. Liang, X. Han, Z. Liu, Adv. Mater. 2019, 31, 1802228.
- 67a) I. Bilecka, M. Niederberger, Nanoscale 2010, 2, 1358; b) C. N. R. Rao, S. R. C. Vivekchand, K. Biswas, A. Govindaraj, Dalton Trans. 2007, 3728.
- 68M. Malmsten, Curr. Opin. Colloid Interface Sci. 2013, 18, 468.
- 69G. Song, Y. Chen, C. Liang, X. Yi, J. Liu, X. Sun, S. Shen, K. Yang, Z. Liu, Adv. Mater. 2016, 28, 7143.
- 70J. Chen, S. Lei, K. Zeng, M. Wang, A. Asif, X. Ge, Nano Res. 2017, 10, 2351.
- 71R. K. Kankala, Y. Kuthati, C.-L. Liu, C.-Y. Mou, C.-H. Lee, RSC Adv. 2015, 5, 86072.
- 72a) H. Wei, E. Wang, Chem. Soc. Rev. 2013, 42, 6060; b) X. Wang, Y. Hu, H. Wei, Inorg. Chem. Front. 2016, 3, 41.
- 73a) Y. Tao, E. Ju, J. Ren, X. Qu, Adv. Mater. 2015, 27, 1097; b) W. He, Y.-T. Zhou, W. G. Wamer, X. Hu, X. Wu, Z. Zheng, M. D. Boudreau, J.-J. Yin, Biomaterials 2013, 34, 765.
- 74C.-P. Liu, T.-H. Wu, C.-Y. Liu, K.-C. Chen, Y.-X. Chen, G.-S. Chen, S.-Y. Lin, Small 2017, 13, 1700278.
- 75a) Z. Chen, J.-J. Yin, Y.-T. Zhou, Y. Zhang, L. Song, M. Song, S. Hu, N. Gu, ACS Nano 2012, 6, 4001; b) J. Li, W. Liu, X. Wu, X. Gao, Biomaterials 2015, 48, 37.
- 76C. Yao, W. Wang, P. Wang, M. Zhao, X. Li, F. Zhang, Adv. Mater. 2018, 30, 1704833.
- 77Y. Chen, H. Zhong, J. Wang, X. Wan, Y. Li, W. Pan, N. Li, B. Tang, Chem. Sci. 2019, 10, 5773.
- 78W. Zhen, Y. Liu, L. Lin, J. Bai, X. Jia, H. Tian, X. Jiang, Angew. Chem., Int. Ed. 2018, 57, 10309.
- 79S. Liang, X. Deng, Y. Chang, C. Sun, S. Shao, Z. Xie, X. Xiao, P. A. Ma, H. Zhang, Z. Cheng, J. Lin, Nano Lett. 2019, 19, 4134.
- 80S.-Y. Yin, G. Song, Y. Yang, Y. Zhao, P. Wang, L.-M. Zhu, X. Yin, X.-B. Zhang, Adv. Funct. Mater. 2019, 29, 1901417.
- 81a) G. Kong, R. D. Braun, M. W. Dewhirst, Cancer Res. 2000, 60, 4440; b) W. Jiang, Y. Huang, Y. An, B. Y. S. Kim, ACS Nano 2015, 9, 8689.
- 82a) B. A. Buhren, H. Schrumpf, N.-P. Hoff, E. Bölke, S. Hilton, P. A. Gerber, Eur. J. Med. Res. 2016, 21, 5; b) H. Alipour, A. Raz, S. Zakeri, N. Dinparast Djadid, Asian Pac. J. Trop. Biomed. 2016, 6, 975.
- 83Q. Zhu, X. Chen, X. Xu, Y. Zhang, C. Zhang, R. Mo, Adv. Funct. Mater. 2018, 28, 1707371.
- 84H. Wang, X. Han, Z. Dong, J. Xu, J. Wang, Z. Liu, Adv. Funct. Mater. 2019, 29, 1902440.
- 85a) K. Xu, F. Lee, S. Gao, M.-H. Tan, M. Kurisawa, J. Controlled Release 2015, 216, 47; b) H. Zhou, Z. Fan, J. Deng, P. K. Lemons, D. C. Arhontoulis, W. B. Bowne, H. Cheng, Nano Lett. 2016, 16, 3268.
- 86S. B. Bankar, M. V. Bule, R. S. Singhal, L. Ananthanarayan, Biotechnol. Adv. 2009, 27, 489.
- 87a) S.-Y. Li, H. Cheng, B.-R. Xie, W.-X. Qiu, J.-Y. Zeng, C.-X. Li, S.-S. Wan, L. Zhang, W.-L. Liu, X.-Z. Zhang, ACS Nano 2017, 11, 7006; b) Z. Yu, P. Zhou, W. Pan, N. Li, B. Tang, Nat. Commun. 2018, 9, 5044.
- 88a) M. V. Liberti, J. W. Locasale, Trends Biochem. Sci. 2016, 41, 211; b) Z. Chen, W. Lu, C. Garcia-Prieto, P. Huang, J. Bioenerg. Biomembr. 2007, 39, 267; c) S. J. Bensinger, H. R. Christofk, Semin. Cell Dev. Biol. 2012, 23, 352.
- 89H. Hao, M. Sun, P. Li, J. Sun, X. Liu, W. Gao, ACS Appl. Mater. Interfaces 2019, 11, 9756.
- 90Y.-H. Zhang, W.-X. Qiu, M. Zhang, L. Zhang, X.-Z. Zhang, ACS Appl. Mater. Interfaces 2018, 10, 15030.
- 91C. Zhang, W. Bu, D. Ni, S. Zhang, Q. Li, Z. Yao, J. Zhang, H. Yao, Z. Wang, J. Shi, Angew. Chem., Int. Ed. 2016, 55, 2101.
- 92H. Ranji-Burachaloo, A. Reyhani, P. A. Gurr, D. E. Dunstan, G. G. Qiao, Nanoscale 2019, 11, 5705.
- 93W. Ke, J. Li, F. Mohammed, Y. Wang, K. Tou, X. Liu, P. Wen, H. Kinoh, Y. Anraku, H. Chen, K. Kataoka, Z. Ge, ACS Nano 2019, 13, 2357.
- 94M. Huo, L. Wang, Y. Chen, J. Shi, Nat. Commun. 2017, 8, 357.
- 95X. Liu, Y. Liu, J. Wang, T. Wei, Z. Dai, ACS Appl. Mater. Interfaces 2019, 11, 23065.
- 96J.-J. Hu, M.-D. Liu, F. Gao, Y. Chen, S.-Y. Peng, Z.-H. Li, H. Cheng, X.-Z. Zhang, Biomaterials 2019, 217, 119303.
- 97a) W.-H. Chen, G.-F. Luo, Q. Lei, S. Hong, W.-X. Qiu, L.-H. Liu, S.-X. Cheng, X.-Z. Zhang, ACS Nano 2017, 11, 1419; b) J. Zhou, M. Li, Y. Hou, Z. Luo, Q. Chen, H. Cao, R. Huo, C. Xue, L. Sutrisno, L. Hao, Y. Cao, H. Ran, L. Lu, K. Li, K. Cai, ACS Nano 2018, 12, 2858.
- 98M.-K. Zhang, C.-X. Li, S.-B. Wang, T. Liu, X.-L. Song, X.-Q. Yang, J. Feng, X.-Z. Zhang, Small 2018, 14, 1803602.
- 99Y. Yang, Y. Lu, P. L. Abbaraju, I. Azimi, C. Lei, J. Tang, M. Jambhrunkar, J. Fu, M. Zhang, Y. Liu, C. Liu, C. Yu, Adv. Funct. Mater. 2018, 28, 1800706.
- 100S. García-Gallego, G. J. L. Bernardes, Angew. Chem., Int. Ed. 2014, 53, 9712.
- 101a) A. C. Kautz, P. C. Kunz, C. Janiak, Dalton Trans. 2016, 45, 18045; b) P. C. Kunz, H. Meyer, J. Barthel, S. Sollazzo, A. M. Schmidt, C. Janiak, Chem. Commun. 2013, 49, 4896.
- 102Y. Wang, Z. Liu, H. Wang, Z. Meng, Y. Wang, W. Miao, X. Li, H. Ren, Acta Biomater. 2019, 92, 241.
- 103a) X. Zhang, G. Tian, W. Yin, L. Wang, X. Zheng, L. Yan, J. Li, H. Su, C. Chen, Z. Gu, Y. Zhao, Adv. Funct. Mater. 2015, 25, 3049; b) J. Xu, F. Zeng, H. Wu, C. Hu, C. Yu, S. Wu, Small 2014, 10, 3750.
- 104W. Fan, N. Lu, P. Huang, Y. Liu, Z. Yang, S. Wang, G. Yu, Y. Liu, J. Hu, Q. He, J. Qu, T. Wang, X. Chen, Angew. Chem., Int. Ed. 2017, 56, 1229.
- 105C. Liu, J. Xing, O. U. Akakuru, L. Luo, S. Sun, R. Zou, Z. Yu, Q. Fang, A. Wu, Nano Lett. 2019, 19, 5674.
- 106N. Kordalivand, D. Li, N. Beztsinna, J. Sastre Torano, E. Mastrobattista, C. F. van Nostrum, W. E. Hennink, T. Vermonden, Chem. Eng. J. 2018, 340, 32.
- 107a) W. Ardelt, B. Ardelt, Z. Darzynkiewicz, Eur. J. Pharmacol. 2009, 625, 181; b) P. A. Leland, R. T. Raines, Chem. Biol. 2001, 8, 405.
- 108R. T. Raines, Chem. Rev. 1998, 98, 1045.
- 109M. Wang, S. Sun, C. I. Neufeld, B. Perez-Ramirez, Q. Xu, Angew. Chem., Int. Ed. 2014, 53, 13444.
- 110H. He, Y. Chen, Y. Li, Z. Song, Y. Zhong, R. Zhu, J. Cheng, L. Yin, Adv. Funct. Mater. 2018, 28, 1706710.
- 111M. Liu, S. Shen, D. Wen, M. Li, T. Li, X. Chen, Z. Gu, R. Mo, Nano Lett. 2018, 18, 2294.
- 112J. Chen, J. Ouyang, Q. Chen, C. Deng, F. Meng, J. Zhang, R. Cheng, Q. Lan, Z. Zhong, ACS Appl. Mater. Interfaces 2017, 9, 24140.
- 113J. Chen, H. He, C. Deng, L. Yin, Z. Zhong, Int. J. Pharm. 2019, 560, 57.
- 114L. Ding, Y. Jiang, J. Zhang, H.-A. Klok, Z. Zhong, Biomacromolecules 2018, 19, 555.
- 115K. Huang, Y. He, Z. Zhu, J. Guo, G. Wang, C. Deng, Z. Zhong, ACS Appl. Mater. Interfaces 2019, 11, 22171.
- 116D. Shao, M. Li, Z. Wang, X. Zheng, Y.-H. Lao, Z. Chang, F. Zhang, M. Lu, J. Yue, H. Hu, H. Yan, L. Chen, W.-F. Dong, K. W. Leong, Adv. Mater. 2018, 30, 1801198.
- 117a) A. G. Porter, R. U. Jänicke, Cell Death Differ. 1999, 6, 99; b) D. C. González-Toro, J.-H. Ryu, R. T. Chacko, J. Zhuang, S. Thayumanavan, J. Am. Chem. Soc. 2012, 134, 6964; c) R. T. Chacko, J. Ventura, J. Zhuang, S. Thayumanavan, Adv. Drug Delivery Rev. 2012, 64, 836; d) J.-H. Ryu, R. T. Chacko, S. Jiwpanich, S. Bickerton, R. P. Babu, S. Thayumanavan, J. Am. Chem. Soc. 2010, 132, 17227.
- 118J. Ventura, S. J. Eron, D. C. González-Toro, K. Raghupathi, F. Wang, J. A. Hardy, S. Thayumanavan, Biomacromolecules 2015, 16, 3161.
- 119K. Dutta, D. Hu, B. Zhao, A. E. Ribbe, J. Zhuang, S. Thayumanavan, J. Am. Chem. Soc. 2017, 139, 5676.
- 120B. Liu, M. Ianosi-Irimie, S. Thayumanavan, ACS Nano 2019, 13, 9408.
- 121K. Palucka, J. Banchereau, Nat. Rev. Cancer 2012, 12, 265.
- 122J. Banchereau, A. K. Palucka, Nat. Rev. Immunol. 2005, 5, 296.
- 123a) Y. Yoshizaki, E. Yuba, N. Sakaguchi, K. Koiwai, A. Harada, K. Kono, Biomaterials 2014, 35, 8186; b) E. Yuba, A. Harada, Y. Sakanishi, S. Watarai, K. Kono, Biomaterials 2013, 34, 3042.
- 124M. Jinek, K. Chylinski, I. Fonfara, M. Hauer, J. A. Doudna, E. Charpentier, Science 2012, 337, 816.
- 125a) R. Rouet, B. A. Thuma, M. D. Roy, N. G. Lintner, D. M. Rubitski, J. E. Finley, H. M. Wisniewska, R. Mendonsa, A. Hirsh, L. de Oñate, J. Am. Chem. Soc. 2018, 140, 6596; b) W. Zhou, H. Cui, L. Ying, X. F. Yu, Angew. Chem., Int. Ed. 2018, 57, 10268.
- 126W. Sun, W. Ji, J. M. Hall, Q. Hu, C. Wang, C. L. Beisel, Z. Gu, Angew. Chem., Int. Ed. 2015, 54, 12029.