Pedro Pires Goulart Guimarães
◽
Celso Tarso Rodrigues Viana
◽
Luciana Pereira
◽
Savio Morato Lacerda Gontijo
◽
Paula Peixoto Campos
◽
...
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.
A novel cancer vaccine strategy with combined IL-18 and HSV-TK gene therapy driven by the hTERT promoter in a murine colorectal cancer model
