Role of poly(epsilon-caprolactone) lipid-core nanocapsules on melanoma-neutrophil crosstalk

Author(s)

Drewes, Carine C. ^[1] ; Alves, Aline de C. S. ^{[2, 3]} ; Hebeda, Cristina B. ^[1] ; Copetti, Isabela ^{[2, 3]} ; Sandri, Silvana ^[1] ; Uchiyama, Mayara K. ^[4] ; Araki, Koiti ^[4] ; Guterres, Silvia S. ^[2] ; Pohlmann, Adriana R. ^{[2, 3]} ; Farsky, Sandra H. ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Ave Prof Lineu Prestes 580 Bloco 13-B, BR-05508900 Sao Paulo - Brazil

^[2] Univ Fed Rio Grande do Sul, Inst Chem, Postgrad Program Pharmaceut Sci, Porto Alegre, RS - Brazil

^[3] Univ Fed Rio Grande do Sul, Inst Chem, Dept Organ Chem, Porto Alegre, RS - Brazil

^[4] Univ Sao Paulo, Inst Chem, Dept Fundamental Chem, Sao Paulo - Brazil

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF NANOMEDICINE; v. 12, p. 7153-7163, 2017.
• Web of Science Citations: 1

Abstract

Metastatic melanoma is an aggressive cancer with increasing incidence and limited therapies in advanced stages. Systemic neutrophilia or abundant neutrophils in the tumor contribute toward its worst prognosis, and the interplay of cancer and the immune system has been shown in tumor development and metastasis. We recently showed the in vivo efficacy of poly(epsilon-caprolactone) lipid-core nanocapsule (LNC) or LNC loaded with acetyleugenol (AcE-LNC) to treat B16F10-induced melanoma in mice. In this study, we investigated whether LNC or AcE-LNC toxicity could involve modifications on crosstalk of melanoma cells and neutrophils. Therefore, melanoma cells (B16F10) were pretreated with vehicle, LNC, AcE or AcE-LNC for 24 h, washed and, further, cocultured for 18 h with peritoneal neutrophils obtained from C57Bl/6 mice. Melanoma cells were able to internalize the LNC or AcE-LNC after 2 h of incubation. LNC or AcE-LNC pretreatments did not cause melanoma cells death, but led melanoma cells to be more susceptible to death in serum deprivation or hypoxia or in the presence of neutrophils. Interestingly, the production of reactive oxygen species (ROS), which causes cell death, was increased by neutrophils in the presence of LNC- and AcE-LNC-pretreated melanoma cells. LNC or AcE-LNC treatments reduced the concentration of transforming growth factor-beta (TGF-beta) in the supernatant of melanoma cells, a known factor secreted by cancer cells to induce pro-tumoral actions of neutrophils in the tumor microenvironment. In addition, we found reduced levels of pro-tumoral chemical mediators VEGF, arginase-1, interleukin-10 (IL-10) and matrix metalloproteinase-9 (MMP-9) in the supernatant of LNC or AcE-LNC-pretreated melanoma cells and cocultured with neutrophils. Overall, our data show that the uptake of LNC or AcE-LNC by melanoma cells affects intracellular mechanisms leading to more susceptibility to death and also signals higher neutrophil antitumoral activity. (AU)

• FAPESP's process: 14/07328-4 - Identification of endogenous pathways for the control of inflammation
• Grantee: Sandra Helena Poliselli Farsky
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 10/19802-1 - Effects of lipid-core nanocapsules with acetyleugenol in melanomas: in vivo and in vitro studies
• Grantee: Carine Cristiane Drewes
• Support Opportunities: Scholarships in Brazil - Doctorate