RESUMO
: The aim of the current study is to present a strategy to improve the efficiency of 5-fluorouracil (5-FU), which is widely used as antineoplastic agent against solid tumors-based on the use of gold nanocarriers to overcome the resistance of colorectal cancer cells. 5-FU was loaded on gold nanoparticles (AuNP) coated with anti-EGFR antibodies in order to target them towards colorectal cancer cells that overexpress epidermal growth factor receptors (EGFR). Physicochemical characterization has shown that AuNP size was approximately 20 nm and that AuNP functionalization led to spherical nanoparticles. Flow cytometry allowed observing that some compounds synthesized by our research group have induced apoptosis/necrosis and impaired the proliferation of colon cancer cell lines 'HCT-116' and 'HT-29'. The antibody/drug combination in AuNP (AuNP 5FU EGFR) has improved the apoptosis rate and impaired cell proliferation in both cell lines, regardless of the exposure time. Overall, these results have shown that AuNP functionalization with monoclonal antibodies focused on delivering 5-FU to tumor cells is an exciting strategy against colorectal cancer.
RESUMO
Although much has been made of the role of HMGB1 acting as an acute damage associated molecular pattern (DAMP) molecule, prompting the response to tissue damage or injury, it is also released at sites of chronic inflammation including sites of infection, autoimmunity, and cancer. As such, the biology is distinguished from homeostasis and acute inflammation by the recruitment and persistence of myeloid derived suppressor cells, T regulatory cells, fibrosis and/or exuberant angiogenesis depending on the antecedents and the other individual inflammatory partners that HMGB1 binds and focuses, including IL-1ß, CXCL12/SDF1, LPS, DNA, RNA, and sRAGE. High levels of HMGB1 released into the extracellular milieu and its persistence in the microenvironment can contribute to the pathogenesis of many if not all autoimmune disorders and is a key factor that drives inflammation further and worsens symptoms. HMGB1 is also pivotal in the maintenance of chronic inflammation and a "wound healing" type of immune response that ultimately contributes to the onset of carcinogenesis and tumor progression. Exosomes carrying HMGB1 and other instructive molecules are released and shape the response of various cells in the chronic inflammatory environment. Understanding the defining roles of REDOX, DAMPs and PAMPs, and the host response in chronic inflammation requires an alternative means for positing HMGB1's central role in limiting and focusing inflammation, distinguishing chronic from acute inflammation.