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Nitric oxide-releasing nanoparticles: synthesis, characterization, and cytotoxicity to tumorigenic cells

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Abstract

Nitric oxide (NO) is involved in several biological processes, including toxicity against tumor cells. The aim of this study was to synthesize, characterize, and evaluate the cytotoxicity of NO-releasing chitosan nanoparticles. A thiol-containing molecule, mercaptosuccinic acid (MSA), was encapsulated (encapsulation efficiency of 99%) in chitosan/sodium tripolyphosphate nanoparticles (CS NPs). The obtained nanoparticles showed an average hydrodynamic size of 108.40 ± 0.96 nm and polydispersity index of 0.26 ± 0.01. MSA-CS NPs were nitrosated leading to S-nitroso-MSA-CS NPs, which act as NO donor. The cytotoxicity of CS NPs, MSA-CS NPs, and S-nitroso-MSA-CS NPs were evaluated in several tumor cells, including human hepatocellular carcinoma (HepG2), mouse melanoma (B16F10), and human chronic myeloid leukemia (K562) cell lines and Lucena-1, a vincristine-resistant K562 cell line. Both CS NPs and MSA-CS NPs did not cause toxic effects in these cells, whereas S-nitroso-MSA-CS NPs caused potent cytotoxic effects in all the tested tumor cell lines. The half-maximal inhibitory concentration values of S-nitroso-MSA-CS NPs were 19.7, 10.5, 22.8, and 27.8 μg·mL−1 for HepG2, B16F10, K562, and Lucena-1 cells, respectively. In contrast, S-nitroso-MSA-CS NPs exhibited lower cytotoxic to non-tumorigenic melanocytes (Melan-A) when compared with melanoma B16F10. Therefore, the results highlight the potential use of NO-releasing CS NPs in antitumor chemotherapy.

Atomic force microscopy of chitosan nanoparticles for nitric oxide release

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Acknowledgements

This work was supported by FAPESP (Proc. 2016/10347-6, 2015/00393-8, 2014/13913-7), the Brazilian Network on Nanotoxicology (Grant number: 552120/2011-1) (MCTI/CNPq), the Laboratory of Nanostructure Synthesis and Biosystem Interactions-Nanobioss (MCTI) (Grant number: 402280-2013), Newton Advanced Fellowship (The Royal Society NA140046), Complexo Laboratorial Nanotecnológico (CLN)–UFABC–SisNano (Grant number: 402289/2013-7). The authors wish to thank Dr. Joyce C. Mello for helpful assistance with cytotoxicity measurements, Prof. Dr. Fabio Furlan Ferreira for his assistance with XRD measurements, Dr. Patrícia Fernanda Andrade for her assistance with scanning electron microscopy measurements, Dr. Juliana S. Bernardes for her assistance with AFM, and Genilce Scopiato Paganotti for revising the manuscript. The authors thank the Brazilian Nanotechnology National Laboratory/Center for Research in Energy and Materials (LNNano/CNPEM) for technical support AFM analyses.

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  1. Exact and Earth Sciences Department, Universidade Federal de São Paulo, Rua São Nicolau, 210, CEP, Diadema, SP, 09913-030, Brazil

    Milena T. Pelegrino & Paula S. Haddad

  2. Center of Natural and Human Sciences, Universidade Federal do ABC, UFABC, Av. dos Estados 5001, CEP Bairro Bangú. Bloco A, Torre 3, Sala 626, Santo André, SP, 09210-580, Brazil

    Milena T. Pelegrino, Letícia C. Silva, Carolina M. Watashi, Tiago Rodrigues & Amedea B. Seabra

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  1. Milena T. Pelegrino
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Pelegrino, M.T., Silva, L.C., Watashi, C.M. et al. Nitric oxide-releasing nanoparticles: synthesis, characterization, and cytotoxicity to tumorigenic cells. J Nanopart Res 19, 57 (2017). https://doi.org/10.1007/s11051-017-3747-4

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