Publication:
Selective topotecan delivery to cancer cells by targeted pH-sensitive mesoporous silica nanoparticles

Loading...
Thumbnail Image
Official URL
Full text at PDC
Publication Date
2016
Advisors (or tutors)
Editors
Journal Title
Journal ISSN
Volume Title
Publisher
Citations
Google Scholar
Research Projects
Organizational Units
Journal Issue
Abstract
Topotecan (TOP), a water-soluble derivative of camptothecin, is a potent antitumor agent that is receiving growing attention for the treatment of several types of cancer. However, one of the major constraints in the clinical use of this drug is its inactivation at the physiological pH of 7.4. Mesoporous silica nanoparticles (MSNs) constitute promising nanocarriers to circumvent this issue. Herein TOP has been encapsulated into MSNs and the nanosystem has been provided with selectivity towards tumor cells, which permits releasing the active form of the molecule at the acidic cell compartments (endo/lysosomes; pH <= 5.5) following nanoparticle internalization. For this purpose, MSNs have been coated with a multifunctional gelatin shell that: (i) protects TOP from hydrolysis and prevents its premature release; (ii) acts as a pH-sensitive layer; and (iii) provides multiple anchoring points for the grafting of targeting ligands, such as folic acid (FA), for selective internalization in tumor cells. In vitro tests demonstrate that cancer cells that overexpress membrane cell surface markers with affinity towards FA, internalize a higher percentage of nanoparticles than healthy cells, which do not overexpress such markers. Moreover, the nanosystems are efficient at killing tumor cells, whereas they do not decrease the viability of normal cells. In contrast, free TOP failed to kill both cell lines, which can be ascribed to the inactivation of the drug. This novel nanodevice constitutes a step forward toward the design of novel weapons to fight against cancer.
Description
RESEARCHER ID M-3378-2014 (María Vallet Regí) ORCID 0000-0002-6104-4889 (María Vallet Regí) RESEARCHER ID B-5081-2017 (Daniel Lozano Borregón) ORCID 0000-0001-5902-9201 (Daniel Lozano Borregón)
Keywords
Citation
1 Y. H. Hsiang, R. Hertzberg, S. Hecht and L. F. Liu, J. Biol. Chem., 1985, 25, 14873. 2 P. D'Arpa and L. F. Liu, Biochim. Biophys. Acta, 1989, 989, 163. 3 J. F. Pizzolato and L. B. Saltz, Lancet, 2003, 361, 2235. 4 V. M. Herben, W. W. ten Bokkel Huinink and J. H. Beijnen, Clin. Pharmacokinet., 1996, 31, 85. 5 P. Tardi, E. Choice, D. Masin, T. Redelmeier, M. Bally and T. D. Madden, Cancer Res., 2000, 60, 3389. 6 J. G. Wall, H. A. Burris 3rd, D. D. Von Hoff, G. Rodriguez, R. Kneuper-Hall, D. Shaffer, T. O'Rourke, T. Brown, G. Weiss, G. Clark, S. J. B. McVea, R. Johnson, C. Friedman, B. Smith, W. S. Mann and J. Kuhn, Anti- Cancer Drugs, 1992, 3, 337. 7 B. Arun and E. P. Frenkel, Expert Opin. Pharmacother., 2001, 2, 491. Fig. 7 Cell viability in contact with different concentrations of TOP (2.5 and 10 mgmL�1) loaded or not into MSN-FA at (a) 24, (b) 48 and (c) 72 hours of cell culture. *p < 0.05 vs. TOP not loaded into MSN-FA (Student's t-test). This journal is © The Royal Society of Chemistry 2016 RSC Adv., 2016, 6, 50923–50932 | 50931 Paper RSC Advances 8 R. J. Gillies, N. Raghunand, M. L. Garc´ıa-Mart´ın and R. A. Gatenby, IEEE Eng. Med. Biol. Mag., 2004, 23, 57. 9 Y.-L. Hao, Y.-L. Deng, Y. Chen, A.-J. Hao, Y. Zhang and K.-Z. Wang, J. Pharm. Pharmacol., 2005, 57, 1279. 10 N. A. Patankar, D. Waterhouse, D. Strutt, M. Anantha and M. B. Bally, Invest. New Drugs, 2013, 31, 46. 11 D. C. Drummond, C. O. Noble, Z. Guo, M. E. Hayes, C. Connolly-Ingram, B. S. Gabriel, B. Hann, B. Liu, J. W. Park, K. Hong, C. C. Benz, J. D. Marks and D. B. Kirpotin, J. Controlled Release, 2010, 141, 13. 12 K. D. Fugit and B. D. Anderson, J. Controlled Release, 2014, 174, 88. 13 L. G. Souza, E. J. Silva, A. L. L. Martins, M. F. Mota, R. C. Braga, E. M. Lima, M. C. Valadares, S. F. Taveira and R. N. Marreto, Eur. J. Pharm. Biopharm., 2011, 79, 189. 14 S. Padhi, M. Mirza, D. Verma, T. Khuroo, A. K. Panda, S. Talegaonkar, R. K. Khar and Z. Iqbal, Drug Delivery, 2015, 1. 15 M. Kim, K. Ock, K. Cho, S.-W. Joo and S. Y. Lee, Chem. Commun., 2012, 48, 4205. 16 M. R. di Nunzio, V. Agostoni, B. Cohen, R. Gref and A. Douhal, J. Med. Chem., 2014, 57, 411. 17 X. Du, B. Shi, J. Liang, J. Bi, S. Dai and S. Z. Qiao, Adv. Mater., 2013, 25, 5981. 18 L. Xing, H. Zheng, Y. Cao and S. Che, Adv. Mater., 2012, 24, 6433. 19 G.-F. Luo, W.-H. Chen, Y. Liu, Q. Lei, R.-X. Zhuo and X.-Z. Zhang, Sci. Rep., 2014, 4, 6064. 20 B. Shen, K. Zhao, S. Ma, D. Yuan and Y. Bai, Chem.–Asian J., 2015, 10, 344. 21 M. Vallet-Reg´ı, A. R´amila, R. P. del Real and J. P´erez-Pariente, Chem. Mater., 2001, 13, 308. 22 M. Vallet-Reg´ı, F. Balas and D. Arcos, Angew. Chem., Int. Ed., 2007, 46, 7548. 23 J. Lu, M. Liong, Z. X. Li, J. I. Zink and F. Tamanoi, Small, 2010, 6, 1794. 24 Y. Zhao, X. Sun, G. Zhang, B. G. Trewyn, I. I. Slowing and V. S. Lin, ACS Nano, 2011, 5, 1366. 25 P. Yang, S. Gai and J. Lin, Chem. Soc. Rev., 2012, 41, 3679. 26 C. Argyo, V. Weiss, C. Braeuchle and T. Bein, Chem. Mater., 2014, 26, 435. 27 E. Aznar, M. Oroval, L. Pascual, J. R. Murgu´ıa, R. Mart´ınez- M´a˜nez and F. Sancen´on, Chem. Rev., 2016, 116, 534. 28 F. Tang, L. Li and D. Chen, Adv. Mater., 2012, 24, 1504. 29 Z. Li, J. C. Barnes, A. Bosoy, J. F. Stoddart and J. I. Zink, Chem. Soc. Rev., 2012, 41, 2590. 30 A. Baeza, E. Guisasola, A. Torres-Pardo, J. M. Gonz´alez- Calbet, G. J. Melen, M. Ram´ırez and M. Vallet-Reg´ı, Adv. Funct. Mater., 2014, 24, 4625. 31 Y. Zhang, C. Y. Ang, M. Li, Y. Tan, Q. Qu, Z. Luo and Y. Zhao, ACS Appl. Mater. Interfaces, 2015, 7, 18179. 32 J. L. Paris, M. V. Caba˜nas, M. Manzano and M. Vallet-Reg´ı, ACS Nano, 2015, 9, 11023. 33 M. Mart´ınez-Carmona, A. Baeza, M. A. Rodr´ıguez-Milla, J. Garc´ıa-Castro and M. Vallet-Reg´ı, J. Mater. Chem. B, 2015, 3, 5746. 34 G. Villaverde, A. Baeza, G. J. Melen, A. Alfranca, M. Ram´ırez and M. Vallet-Reg´ı, J. Mater. Chem. B, 2015, 3, 4831. 35 M. R. Villegas, A. Baeza and M. Vallet-Reg´ı, ACS Appl. Mater. Interfaces, 2015, 7, 24075. 36 M. Mart´ınez-Carmona, M. Colilla and M. Vallet-Reg´ı, Nanomaterials, 2015, 5, 1906. 37 A. Baeza, M. Manzano, M. Colilla and M. Vallet-Reg´ı, Biomater. Sci., 2016, 4, 803. 38 W. A. Franklin, M. Waintrub, D. Edwards, K. Christensen, P. Prendegrast, J. Woods, P. A. Bunn and J. F. Kolhouse, Int. J. Cancer, 1994, 8, 89. 39 S. D. Weitman, R. H. Lark, L. R. Coney, D. W. Fort, V. Frasca, V. R. Zurawski Jr and B. A. Kamen, Cancer Res., 1992, 52, 3396. 40 J. Lu, Z. Li, J. I. Zink and F. Tamanoi, Nanomedicine: Nanotechnology, Biology and Medicine, 2012, 8, 212. 41 Y. Hattori and Y. Maitani, J. Controlled Release, 2004, 97, 173. 42 Z. Zou, D. He, X. He, K. Wang, X. Yang, Z. Qing and Q. Zhou, Langmuir, 2013, 29, 12804. 43 Y. Tabata and Y. Ikada, Adv. Drug Delivery Rev., 1998, 31, 287. 44 Z. Cheng, Y. Dai, X. Kang, C. Li, S. Huang, H. Lian, Z. Hou, P. Ma and J. Lin, Biomaterials, 2014, 35, 6359. 45 O. Terasaki, T. Ohsuna, Z. Liu, Y. Sakamoto and A. E. Garc´ıa- Bennet, Stud. Surf. Sci. Catal., 2004, 148, 261. 46 M. Mart´ınez-Carmona, M. Colilla, M. L. Ruiz-Gonz´alez, J. M. Gonz´alez-Calbet and M. Vallet-Reg´ı, Microporous Mesoporous Mater., 2016, 225, 399. 47 B. Gonz´alez, M. Colilla, C. L´opez de Laorden and M. Vallet- Reg´ı, J. Mater. Chem., 2009, 19, 9012. 48 A. J. Kuijpers, G. H. Engbers, J. Krijgsveld, S. A. Zaat, J. Dankert and J. Feijen, J. Biomater. Sci., Polym. Ed., 2000, 11, 225. 49 T. Ito, L. Sun, M. A. Bevan and R. M. Crooks, Langmuir, 2004, 20, 6940. 50 T. Chen, W. Wu, H. Xiao, Y. Chen, M. Chen and J. Li, ACS Macro Lett., 2016, 5, 55. 51 F. Balas, M. Manzano, M. Colilla and M. Vallet-Reg´ı, Acta Biomater., 2008, 4, 514. 52 S. Young, M. Wong, Y. Tabata and A. G. Mikos, J. Controlled Release, 2005, 109, 256. 53 B. Gaihre, M. S. Khil, D. R. Lee and H. Y. Kim, Int. J. Pharm., 2009, 365, 180. 54 A. Mart´ınez-Ruvalcaba, F. Becerra-Bracamontes, J. C. S´anchez-D´ıaz and A. Gonz´alez-´A lvarez, Polym. Bull., 2009, 62, 539. 55 M. Vallet-Reg´ı, M. Colilla and B. Gonz´alez, Chem. Soc. Rev., 2011, 40, 596. 56 M. Wu, W. Gunning and M. Ratnam, Cancer Epidemiol., Biomarkers Prev., 1999, 8, 775. 57 F. Shen, J. F. Ross, X. Wang and M. Ratnam, Biochemistry, 1994, 33, 1209.
Collections