NANOMEDICINA: APLICACIONES EN EL DIAGNÓSTICO Y TRATAMIENTO DEL CÁNCER
Palabras clave:
Nanotecnología; cáncer; tratamiento; diagnóstico.Resumen
El estudio es una revisión integradora de la literatura, con el objetivo de describir el uso de la nanotecnología para el cribado, diagnóstico y tratamiento de diversos tipos de neoplasias, considerando que la herramienta ha mostrado resultados satisfactorios, con una mejora en el pronóstico de los pacientes. Para la recolección de datos se utilizaron las bases de datos SCIELO y PUBMED, en las que se encontraron 1.643 artículos. De estos, solo 44 abordaron directamente aspectos relacionados con la nanotecnología en el diagnóstico y tratamiento del cáncer y se ajustaron a los criterios de inclusión. Los hallazgos sugirieron que la nanotecnología es una herramienta útil en el diagnóstico temprano y el tratamiento efectivo para varios tipos de cáncer, ya que tiene especificidad para muchos tipos de células alteradas, administración farmacológica dirigida, lo que reduce los efectos secundarios y mejora la eficacia del fármaco. También se sugiere que esta tecnología tiene una menor probabilidad de resistencia a los medicamentos de quimioterapia. Considerando los beneficios de la nanotecnología como herramienta eficiente en el diagnóstico y tratamiento de diversas neoplasias, es necesario ampliar el conocimiento sobre el tema entre la población y los profesionales de la salud.
Palabras clave: Nanotecnología; cáncer; tratamiento; diagnóstico.
Referencias
1. Brasil.Organização Mundial Da Saúde/Organizacão Pan-Americana De Saúde OMS/OPAS. Folha informativa-câncer. Brasília, Brasil: 2018.
2. Bittencourt R, scaletzky A, boehl JAR. Perfil epidemiológico do câncer na rede pública em Porto Alegre-RS. Rev bras cancerol, 2004; 50(2): 95-101.
3. Helmy KY, Patel SA, Nahas GR, et al. Cancer immunotherapy: accomplishments to date and future promise. Therapeutic delivery, 2013; 4(10): 1307-1320.
4. Cancino J, marangoni V, Zucolotto V. Nanotecnologia em medicina: aspectos fundamentais e principais preocupações. Química Nova, 2014; 37(3): 521-526.
5. Darwiche K, Zarogoulidis P, Krauss L, et al. “One-stop shop” spectral imaging for rapid on-site diagnosis of lung cancer: a future concept in nano-oncology. International journal of nanomedicine, 2013; v.8, p.4533.
6. Rizvi SB, Rouhi S, Taniguchi S, et al. Near-infrared quantum dots for HER2 localization and imaging of cancer cells. International journal of nanomedicine. 2014; v. 9, p. 1323.
7. Halo TL, McMahon KM, Angeloni NL, et al. NanoFlares for the detection, isolation, and culture of live tumor cells from human blood. Proceedings of the National Academy of Sciences, 2014; 111(48): 17104-17109.
8. You M, Zhu G, Chen T, et al. Programmable and multiparameter DNA-based logic platform for cancer recognition and targeted therapy. Journal of the American Chemical Society, 2015; 137(2): 667-674.
9. Cui D, Zhang C, Liu B, et al. Regression of gastric cancer by systemic injection of RNA nanoparticles carrying both ligand and siRNA. Scientific reports, 2015; v. 5, p. 10726.
10. Sweeney SK, Luo Y, O’Donnell MA, et al. Nanotechnology and cancer: improving real-time monitoring and staging of bladder cancer with multimodal mesoporous silica nanoparticles. Cancer nanotechnology,2016; 7(1) 3.
11. Dobiasch S, Szanyi S, Kjaev A, et al. Synthesis and functionalization of protease-activated nanoparticles with tissue plasminogen activator peptides as targeting moiety and diagnostic tool for pancreatic cancer. Journal of nanobiotechnology, 2016;14(1), 81.
12. Khaniabadi PM, Shahbazi-Gahrouei D, Jaafar M S, et al. Magnetic iron oxide nanoparticles as T2 MR imaging contrast agent for detection of breast cancer (MCF-7) cell. Avicenna journal of medical biotechnology, 2017; 9(4) 181.
13. Dapkute D, Steponkiene S, Bulotiene D, et al. Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors. International Journal of Nanomedicine, 2017; v.12, p. 8129.
14. Wu X, Xiao T, Luo Z, et al.A micro-/nano-chip and quantum dots-based 3D cytosensor for quantitative analysis of circulating tumor cells. Journal of nanobiotechnology, 2018; 16(1) 1-9.
15. Garrigue P, Tang J, Ding L, et al. Self-assembling supramolecular dendrimer nanosystem for PET imaging of tumors. Proceedings of the National Academy of Sciences, 2018; 115(45): 11454-11459.
16. Affram K, Smith T, Helsper S, et al. Comparative study on contrast enhancement of Magnevist and Magnevist-loaded nanoparticles in pancreatic cancer PDX model monitored by MRI. Cancer Nanotechnology, 2020; 11(1): 1-14.
17. Singh AK, Hahn MA, Gutwein LG, et al. Multi-dye theranostic nanoparticle platform for bioimaging and cancer therapy. International journal of nanomedicine, 2012; v.7, p. 2739.
18. Dadgar N, Esfahani MKM, Torabi S, et al. Effects of nanoliposomal and pegylated nanoliposomal artemisinin in treatment of breast cancer. Indian journal of clinical biochemistry, 2014; 29(4): 501-504.
19. Wei T, Chen C, Liu J, et al. Anticancer drug nanomicelles formed by self-assembling amphiphilic dendrimer to combat cancer drug resistance. Proceedings of the National Academy of Sciences, 2015; 112(10): 2978-2983.
20. Gurunathan S, Park JH, Han JW, et al. Comparative assessment of the apoptotic potential of silver nanoparticles synthesized by Bacillus tequilensis and Calocybe indica in MDA-MB-231 human breast cancer cells: targeting p53 for anticancer therapy. International journal of nanomedicine, 2015; v10, p. 4203.
21. Fang YQ, Wu JY, Li TC, et al. Nanoparticle mediated chemotherapy of hormone refractory prostate cancer with a novel combi-molecule. American journal of translational research, 2015; 7(8): 1440.
22. Kalanaky S, Hafizi M, Fakharzadeh S, et al. BCc1, the novel antineoplastic nanocomplex, showed potent anticancer effects in vitro and in vivo. Drug design, development and therapy, 2016; v. 10, p. 59.
23. Guo JUN, Wu SH, Ren WG, et al. Anticancer activity of bicalutamide-loaded PLGA nanoparticles in prostate cancers. Experimental and therapeutic medicine, 2015; 10(6): 2305-2310.
24. Shu D, Li H, Shu Y, et al. Systemic delivery of anti-miRNA for suppression of triple negative breast cancer utilizing RNA nanotechnology. ACS nano, 2015; 9(10): 9731-9740.
25. Zhang M, Xiao B, Wang H, et al. Edible ginger-derived nano-lipids loaded with doxorubicin as a novel drug-delivery approach for colon cancer therapy. Molecular Therapy, 2016; 24(10): 1783-1796.
26. Drewes CC, Fiel LA, Bexiga CG, et al. Novel therapeutic mechanisms determine the effectiveness of lipid-core nanocapsules on melanoma models. International journal of nanomedicine, 2016; v. 11, p. 1261.
27. Li Y, Lin Z, Zhao M, et al. Multifunctional selenium nanoparticles as carriers of HSP70 siRNA to induce apoptosis of HepG2 cells. International journal of nanomedicine, 2016; v. 11, p. 3065.
28. Hassan CE, Webster TJ. The effect of red-allotrope selenium nanoparticles on head and neck squamous cell viability and growth. International journal of nanomedicine, 2016; v. 11, p. 3641.
29. Zhang M, Xiao B, Wang H, et al. Edible ginger-derived nano-lipids loaded with doxorubicin as a novel drug-delivery approach for colon cancer therapy. Molecular Therapy, 2016; 24(10): 1783-1796.
30. Yaari Z, Da Silva D, Zinger A, et al. Theranostic barcoded nanoparticles for personalized cancer medicine. Nature communications, 2016; 7(1): 1-10.
31. Manivasagan P, Bui NQ, Bharathiraja S, et al. Multifunctional biocompatible chitosan-polypyrrole nanocomposites as novelagents for photoacoustic imaging-guided photothermal ablation of cancer. Scientific reports, 2017; v. 7, p. 43593.
32. Kim YH, Min KH, Wang Z, et al. Development of sialic acid-coated nanoparticles for targeting cancer and efficient evasion of the immune system. Theranostics, 2017; 7(4): 962.
33. Vinhas R; Fernandes AR; Baptista PV. Gold Nanoparticles for BCR-ABL1 gene silencing: Improving tyrosine kinase inhibitor efficacy in chronic myeloid leukemia. Molecular Therapy-Nucleic Acids, 2017; v. 7, p. 408-416.
34. Shen S, Li Y, Xiao Y, et al. Folate-conjugated nanobubbles selectively target and kill cancer cells via ultrasound-triggered intracellular explosion. Biomaterials, 2018; v. 181, p. 293-306.
35. Marino A, Battaglini M, De Pasquale D, et al. Ultrasound-activated piezoelectric nanoparticles inhibit proliferation of breast cancer cells. Scientific reports, 2018; 8(1): 1-13.
36. Kheirkhah P, Denyer S, Bhimani AD, et al. Magnetic drug targeting: a novel treatment for intramedullary spinal cord tumors. Scientific reports, 2018; 8(1): 1-9.
37. Ma J, Kala S, Yung S, et al. Blocking Stemness and Metastatic Properties of Ovarian Cancer Cells by Targeting p70S6K with Dendrimer Nanovector-Based siRNA Delivery. Molecular Therapy 2018; 26(1): 70-83.
38. Guo X, Qu J, Zhu C, Li W, et al. Synchronous delivery of oxygen and photosensitizer for alleviation of hypoxia tumor microenvironment and dramatically enhanced photodynamic therapy. Drug delivery, 2018; 25(1): 585-599.
39. Alyafee YA, Alaamery M, Bawazeer S, et al. Preparation of anastrozole loaded PEG-PLA nanoparticles: evaluation of apoptotic response of breast cancer cell lines. International Journal of Nanomedicine, 2018; v. 13, p. 199.
40. Bai F, Yin Y, Chen T, et al. Development of liposomal pemetrexed for enhanced therapy against multidrug resistance mediated by ABCC5 in breast cancer. International journal of nanomedicine 2018; v. 13, p. 1327.
41. Martínez-Torres AC, Zarate-Triviño DG, Lorenzo-Anota HY, et al. Chitosan gold nanoparticles induce cell death in HeLa and MCF-7 cells through reactive oxygen species production. International journal of nanomedicine, 2018; v. 13, p. 3235.
42. Abou-El-Naga AM, Mutawa G, El-Sherbiny IM, et al. Activation of polymeric nanoparticle intracellular targeting overcomes chemodrug resistance in human primary patient breast cancer cells. International journal of nanomedicine, 2018; v. 13, p. 8153.
43. Higuchi T, Kawaguchi K, Miyake K, et al. The combination of gemcitabine and nab-paclitaxel as a novel effective treatment strategy for undifferentiated soft-tissue sarcoma in a patient-derived orthotopic xenograft (PDOX) nude-mouse model. Biomedicine & Pharmacotherapy, 2019; v. 111, p. 835-840.
44. Xu Y, Pang L, Wang H, et al. Specific delivery of delta-5-desaturase siRNA via RNA nanoparticles supplemented with dihomo-γ-linolenic acid for colon cancer suppression. Redox biology, 2019; v. 21, p. 101085.
45. Khiavi MA, Safary A, Barar J, et al. PEGylated gold nanoparticles-ribonuclease induced oxidative stress and apoptosis in colorectal cancer cells. BioImpacts: BI, 2020; 10(1): 27.
46. Ishiguro K, Yan IK, Lewis‐Tuffin L, et al. Targeting Liver Cancer Stem Cells Using Engineered Biological Nanoparticles for the Treatment of Hepatocellular Cancer. Hepatology communications, 2020; 4(2): 298-313.
47. Nalepa P, Gawecki R, Szewczyk G, et al. A [60] fullerene nanoconjugate with gemcitabine: synthesis, biophysical properties and biological evaluation for treating pancreatic cancer. Cancer Nanotechnology, 2020; 11(1): 1-21.
48. Wiranowska M, Singh R, Falahat R, et al. Preferential drug delivery to tumor cells than normal cells using a tunable niosome–chitosan double package nanodelivery system: a novel in vitro model. Cancer Nanotechnology, 2020; v. 11, p. 1-20.
49. González-López MA, Gutiérrez-Cárdenas EM, Sánchez-Cruz C, et al. Reducing the effective dose of cisplatin using gold nanoparticles as carriers. Cancer Nanotechnology, 2020; v. 11, p. 1-15.
50. Khoobchandani M, Katti KK, Karikachery AR, et al. New Approaches in Breast Cancer Therapy Through Green Nanotechnology and Nano-Ayurvedic Medicine–Pre-Clinical and Pilot Human Clinical Investigations. International Journal of Nanomedicine, 2020; v. 15, p. 181.
2. Bittencourt R, scaletzky A, boehl JAR. Perfil epidemiológico do câncer na rede pública em Porto Alegre-RS. Rev bras cancerol, 2004; 50(2): 95-101.
3. Helmy KY, Patel SA, Nahas GR, et al. Cancer immunotherapy: accomplishments to date and future promise. Therapeutic delivery, 2013; 4(10): 1307-1320.
4. Cancino J, marangoni V, Zucolotto V. Nanotecnologia em medicina: aspectos fundamentais e principais preocupações. Química Nova, 2014; 37(3): 521-526.
5. Darwiche K, Zarogoulidis P, Krauss L, et al. “One-stop shop” spectral imaging for rapid on-site diagnosis of lung cancer: a future concept in nano-oncology. International journal of nanomedicine, 2013; v.8, p.4533.
6. Rizvi SB, Rouhi S, Taniguchi S, et al. Near-infrared quantum dots for HER2 localization and imaging of cancer cells. International journal of nanomedicine. 2014; v. 9, p. 1323.
7. Halo TL, McMahon KM, Angeloni NL, et al. NanoFlares for the detection, isolation, and culture of live tumor cells from human blood. Proceedings of the National Academy of Sciences, 2014; 111(48): 17104-17109.
8. You M, Zhu G, Chen T, et al. Programmable and multiparameter DNA-based logic platform for cancer recognition and targeted therapy. Journal of the American Chemical Society, 2015; 137(2): 667-674.
9. Cui D, Zhang C, Liu B, et al. Regression of gastric cancer by systemic injection of RNA nanoparticles carrying both ligand and siRNA. Scientific reports, 2015; v. 5, p. 10726.
10. Sweeney SK, Luo Y, O’Donnell MA, et al. Nanotechnology and cancer: improving real-time monitoring and staging of bladder cancer with multimodal mesoporous silica nanoparticles. Cancer nanotechnology,2016; 7(1) 3.
11. Dobiasch S, Szanyi S, Kjaev A, et al. Synthesis and functionalization of protease-activated nanoparticles with tissue plasminogen activator peptides as targeting moiety and diagnostic tool for pancreatic cancer. Journal of nanobiotechnology, 2016;14(1), 81.
12. Khaniabadi PM, Shahbazi-Gahrouei D, Jaafar M S, et al. Magnetic iron oxide nanoparticles as T2 MR imaging contrast agent for detection of breast cancer (MCF-7) cell. Avicenna journal of medical biotechnology, 2017; 9(4) 181.
13. Dapkute D, Steponkiene S, Bulotiene D, et al. Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors. International Journal of Nanomedicine, 2017; v.12, p. 8129.
14. Wu X, Xiao T, Luo Z, et al.A micro-/nano-chip and quantum dots-based 3D cytosensor for quantitative analysis of circulating tumor cells. Journal of nanobiotechnology, 2018; 16(1) 1-9.
15. Garrigue P, Tang J, Ding L, et al. Self-assembling supramolecular dendrimer nanosystem for PET imaging of tumors. Proceedings of the National Academy of Sciences, 2018; 115(45): 11454-11459.
16. Affram K, Smith T, Helsper S, et al. Comparative study on contrast enhancement of Magnevist and Magnevist-loaded nanoparticles in pancreatic cancer PDX model monitored by MRI. Cancer Nanotechnology, 2020; 11(1): 1-14.
17. Singh AK, Hahn MA, Gutwein LG, et al. Multi-dye theranostic nanoparticle platform for bioimaging and cancer therapy. International journal of nanomedicine, 2012; v.7, p. 2739.
18. Dadgar N, Esfahani MKM, Torabi S, et al. Effects of nanoliposomal and pegylated nanoliposomal artemisinin in treatment of breast cancer. Indian journal of clinical biochemistry, 2014; 29(4): 501-504.
19. Wei T, Chen C, Liu J, et al. Anticancer drug nanomicelles formed by self-assembling amphiphilic dendrimer to combat cancer drug resistance. Proceedings of the National Academy of Sciences, 2015; 112(10): 2978-2983.
20. Gurunathan S, Park JH, Han JW, et al. Comparative assessment of the apoptotic potential of silver nanoparticles synthesized by Bacillus tequilensis and Calocybe indica in MDA-MB-231 human breast cancer cells: targeting p53 for anticancer therapy. International journal of nanomedicine, 2015; v10, p. 4203.
21. Fang YQ, Wu JY, Li TC, et al. Nanoparticle mediated chemotherapy of hormone refractory prostate cancer with a novel combi-molecule. American journal of translational research, 2015; 7(8): 1440.
22. Kalanaky S, Hafizi M, Fakharzadeh S, et al. BCc1, the novel antineoplastic nanocomplex, showed potent anticancer effects in vitro and in vivo. Drug design, development and therapy, 2016; v. 10, p. 59.
23. Guo JUN, Wu SH, Ren WG, et al. Anticancer activity of bicalutamide-loaded PLGA nanoparticles in prostate cancers. Experimental and therapeutic medicine, 2015; 10(6): 2305-2310.
24. Shu D, Li H, Shu Y, et al. Systemic delivery of anti-miRNA for suppression of triple negative breast cancer utilizing RNA nanotechnology. ACS nano, 2015; 9(10): 9731-9740.
25. Zhang M, Xiao B, Wang H, et al. Edible ginger-derived nano-lipids loaded with doxorubicin as a novel drug-delivery approach for colon cancer therapy. Molecular Therapy, 2016; 24(10): 1783-1796.
26. Drewes CC, Fiel LA, Bexiga CG, et al. Novel therapeutic mechanisms determine the effectiveness of lipid-core nanocapsules on melanoma models. International journal of nanomedicine, 2016; v. 11, p. 1261.
27. Li Y, Lin Z, Zhao M, et al. Multifunctional selenium nanoparticles as carriers of HSP70 siRNA to induce apoptosis of HepG2 cells. International journal of nanomedicine, 2016; v. 11, p. 3065.
28. Hassan CE, Webster TJ. The effect of red-allotrope selenium nanoparticles on head and neck squamous cell viability and growth. International journal of nanomedicine, 2016; v. 11, p. 3641.
29. Zhang M, Xiao B, Wang H, et al. Edible ginger-derived nano-lipids loaded with doxorubicin as a novel drug-delivery approach for colon cancer therapy. Molecular Therapy, 2016; 24(10): 1783-1796.
30. Yaari Z, Da Silva D, Zinger A, et al. Theranostic barcoded nanoparticles for personalized cancer medicine. Nature communications, 2016; 7(1): 1-10.
31. Manivasagan P, Bui NQ, Bharathiraja S, et al. Multifunctional biocompatible chitosan-polypyrrole nanocomposites as novelagents for photoacoustic imaging-guided photothermal ablation of cancer. Scientific reports, 2017; v. 7, p. 43593.
32. Kim YH, Min KH, Wang Z, et al. Development of sialic acid-coated nanoparticles for targeting cancer and efficient evasion of the immune system. Theranostics, 2017; 7(4): 962.
33. Vinhas R; Fernandes AR; Baptista PV. Gold Nanoparticles for BCR-ABL1 gene silencing: Improving tyrosine kinase inhibitor efficacy in chronic myeloid leukemia. Molecular Therapy-Nucleic Acids, 2017; v. 7, p. 408-416.
34. Shen S, Li Y, Xiao Y, et al. Folate-conjugated nanobubbles selectively target and kill cancer cells via ultrasound-triggered intracellular explosion. Biomaterials, 2018; v. 181, p. 293-306.
35. Marino A, Battaglini M, De Pasquale D, et al. Ultrasound-activated piezoelectric nanoparticles inhibit proliferation of breast cancer cells. Scientific reports, 2018; 8(1): 1-13.
36. Kheirkhah P, Denyer S, Bhimani AD, et al. Magnetic drug targeting: a novel treatment for intramedullary spinal cord tumors. Scientific reports, 2018; 8(1): 1-9.
37. Ma J, Kala S, Yung S, et al. Blocking Stemness and Metastatic Properties of Ovarian Cancer Cells by Targeting p70S6K with Dendrimer Nanovector-Based siRNA Delivery. Molecular Therapy 2018; 26(1): 70-83.
38. Guo X, Qu J, Zhu C, Li W, et al. Synchronous delivery of oxygen and photosensitizer for alleviation of hypoxia tumor microenvironment and dramatically enhanced photodynamic therapy. Drug delivery, 2018; 25(1): 585-599.
39. Alyafee YA, Alaamery M, Bawazeer S, et al. Preparation of anastrozole loaded PEG-PLA nanoparticles: evaluation of apoptotic response of breast cancer cell lines. International Journal of Nanomedicine, 2018; v. 13, p. 199.
40. Bai F, Yin Y, Chen T, et al. Development of liposomal pemetrexed for enhanced therapy against multidrug resistance mediated by ABCC5 in breast cancer. International journal of nanomedicine 2018; v. 13, p. 1327.
41. Martínez-Torres AC, Zarate-Triviño DG, Lorenzo-Anota HY, et al. Chitosan gold nanoparticles induce cell death in HeLa and MCF-7 cells through reactive oxygen species production. International journal of nanomedicine, 2018; v. 13, p. 3235.
42. Abou-El-Naga AM, Mutawa G, El-Sherbiny IM, et al. Activation of polymeric nanoparticle intracellular targeting overcomes chemodrug resistance in human primary patient breast cancer cells. International journal of nanomedicine, 2018; v. 13, p. 8153.
43. Higuchi T, Kawaguchi K, Miyake K, et al. The combination of gemcitabine and nab-paclitaxel as a novel effective treatment strategy for undifferentiated soft-tissue sarcoma in a patient-derived orthotopic xenograft (PDOX) nude-mouse model. Biomedicine & Pharmacotherapy, 2019; v. 111, p. 835-840.
44. Xu Y, Pang L, Wang H, et al. Specific delivery of delta-5-desaturase siRNA via RNA nanoparticles supplemented with dihomo-γ-linolenic acid for colon cancer suppression. Redox biology, 2019; v. 21, p. 101085.
45. Khiavi MA, Safary A, Barar J, et al. PEGylated gold nanoparticles-ribonuclease induced oxidative stress and apoptosis in colorectal cancer cells. BioImpacts: BI, 2020; 10(1): 27.
46. Ishiguro K, Yan IK, Lewis‐Tuffin L, et al. Targeting Liver Cancer Stem Cells Using Engineered Biological Nanoparticles for the Treatment of Hepatocellular Cancer. Hepatology communications, 2020; 4(2): 298-313.
47. Nalepa P, Gawecki R, Szewczyk G, et al. A [60] fullerene nanoconjugate with gemcitabine: synthesis, biophysical properties and biological evaluation for treating pancreatic cancer. Cancer Nanotechnology, 2020; 11(1): 1-21.
48. Wiranowska M, Singh R, Falahat R, et al. Preferential drug delivery to tumor cells than normal cells using a tunable niosome–chitosan double package nanodelivery system: a novel in vitro model. Cancer Nanotechnology, 2020; v. 11, p. 1-20.
49. González-López MA, Gutiérrez-Cárdenas EM, Sánchez-Cruz C, et al. Reducing the effective dose of cisplatin using gold nanoparticles as carriers. Cancer Nanotechnology, 2020; v. 11, p. 1-15.
50. Khoobchandani M, Katti KK, Karikachery AR, et al. New Approaches in Breast Cancer Therapy Through Green Nanotechnology and Nano-Ayurvedic Medicine–Pre-Clinical and Pilot Human Clinical Investigations. International Journal of Nanomedicine, 2020; v. 15, p. 181.
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2021-03-01
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Declaro que os conteúdos apresentados nos artigos e demais trabalhos são de minha autoria e tenho total responsabilidade sobre os mesmos, os quais estou cedendo os direitos autorais à Revista Saúde e Meio Ambiente, para fins de divulgação científica em qualquer meio disponível.
