Palestrante
Descrição
Cancer is the most recurrent chronic diseases in the world. (1) In this scenario, human pancreatic carcinoma is amid the neoplasias with the highest number of deaths, and the frequency of relapses demand novel therapeutic intervention. (1) The present study aims the development of nanocarriers to transport two first-line drugs used in clinical treatment (gemcitabine and paclitaxel) into tumor cells using the main components from plasma membrane of pancreatic neoplasms. In cancer cell line and healthy cell, nanoparticles were tested in vitro for particle internalization, and cytotoxic activity of Gemcitabine/Paclitaxel incorporated on nanocarriers. Moreover, particles were labeled with fluorescein isothiocyanate, a fluorescent substance used to evidence internalization by target cells. In order to observe particle specificity, nanocarriers were exposed to PANC-1 cells (human pancreatic tumor), HEPA-RG cells (healthy phenotype liver cell line) and peripheral blood monocytes from healthy donors. Adhesion/internalization was investigated by flow cytometry and the cytotoxic activity of immobilized drug was analyzed by methyl tetrazolium (MTT) reduction and cell viability by Annexin V (apoptosis) and 7AAD (cell death) labeling. The main factor that contributes to neoplastic cells growth and expansion is their ability to modulate tumor microenvironment and evade immune surveillance. (2) Nanocomposites can prevent the production of immunosuppressive cytokines and increase the activity of the main mechanisms of cellular immunity. (3) We also study the nanocarriers ability to carrier immunomodulatory agents, both inside tumor cells and immunocompetent cells. Therefore, nanoparticles were used to deliver antineoplastic agents to cancer cells and antigenic material to antigen presenting cells to modulate the activity of immune system, establishing a pro-inflammatory response in tumor sites.
Acknowledgements:
FAPESP (2018/12670-4), CNPq (142285/2017-0).
Referências
1 BRAY, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, v. 68, n. 6, p. 394-424, Nov./Dec. 2018.
2 BEATTY, G. L.; GLADNEY, W. L. Immune escape mechanisms as a guide for cancer immunotherapy. Clinical Cancer Research, v. 21, n. 4, p. 687-692, Feb. 2015.
3 SONG, H. et al. Injectable polypeptide hydrogel for dual-delivery of antigen and TLR3 agonist to modulate dendritic cells in vivo and enhance potent cytotoxic T-lymphocyte response against melanoma. Biomaterials, v. 159, p. 119-129, Mar. 2018. doi: 10.1016/j.biomaterials.2018.01.004.
| Apresentação do trabalho acadêmico para o público geral | Não |
|---|---|
| Subárea | Nanotoxicologia e Nanomedicina |
