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Sulfonamide-Functionalized Polymeric Nanoparticles For Enhanced In Vivo Colorectal Cancer Therapy

Author(s):

Pedro Pires Goulart Guimarães, Celso Tarso Rodrigues Viana, Luciana Xavier Pereira, Savio Morato Lacerda Gontijo, Paula Peixoto Campos, Silvia Passos Andrade, Robson A. S. Santos and Rubén D. Sinisterra*  

Abstract:


Background: Colorectal cancer (CRC) is the third most common cancer in the world. 5-Fluorouracil (5-FU) is a conventional and most effective drug used in the clinic for the treatment of CRC. However, the clinical use of 5-FU is limited due to the acquired resistance and systemic toxicity, such as hepatotoxicity and gastrointesti-nal toxicity.

Objective: Recent advances in nanomedicine are being exploited to develop nanoparticle platforms to overcome resistance and therapeutic delivery of active molecules. Here, we develop 5-FU loaded sulfadiazine-poly(lactide-co-glycolide) nanoparticles (SUL-PLGA NPs) to be applied in the colorectal cancer model.

Methods: We assessed the in vivo efficacy of the SUL-PLGA NPs to enhance the antitumor effect of 5-FU.

Results: In vivo treatment with 5-FU-SUL-PLGA NPs significantly reduced tumor growth in a colon cancer xen-ograft model compared to free 5-FU and 5-FU loaded non-targeted NPs. Treatment with 5-FU-SUL-PLGA NPs also increased blood vessel diameters within tumors, which could act in conjunction to enhance antitumor effi-cacy. In addition, 5-FU-SUL-PLGA NPs significantly reduced liver mass and lung mass, which are the most common metastasis sites of CRC, and decreased liver hepatotoxicity compared to free 5-FU drug and 5-FU loaded non-targeted NPs.

Conclusion: Our findings suggest that the use of 5-FU-SUL-PLGA NPs is a promising strategy to enhance 5-FU efficacy against CRC.

Keywords:

PLGA, polymeric nanoparticles, sulfonamide, drug delivery, colorectal cancer, cancer therapy

Affiliation:

Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Pampulha, CEP 31270-901, Belo Horizonte - MG, Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Pampulha, CEP 31270-901, Belo Horizonte - MG, Nursing Department, Universidade Federal de Alagoas, Campus Arapiraca. Av. Manoel Severino Barbosa - Bom Sucesso, CEP 57309-005, Arapiraca - AL, Department of Restorative Dentistry, Faculty of Dentistry, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Pampulha, CEP 31270-901, Belo Horizonte-MG, Department of General Pathology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Pampulha, CEP 31270-901, Belo Horizonte - MG, Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Pampulha, CEP 31270-901, Belo Horizonte - MG, Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, Pampulha, CEP 31270-901, Belo Horizonte - MG, Chemistry Department, Institute of Exact Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, CEP 31270-901, Belo Horizonte – MG



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