Antitumor activity and systemic effects of PVM/MA-shelled selol nanocapsules in lung adenocarcinoma-bearing mice

Abstract

Selol is a semi-synthetic compound containing selenite that is effective against cancerous cells and safer for clinical applications in comparison with other inorganic forms of selenite. Recently, we have developed a formulation of poly(methyl vinyl ether-co-maleic anhydride)-shelled selol nanocapsules (SPN), which reduced the proliferative activity of lung adenocarcinoma cells and presented little deleterious effects on normal cells in in vitro studies. In this study, we report on the antitumor activity and systemic effects induced by this formulation in chemically induced lung adenocarcinoma-bearing mice. The in vivo antitumor activity of the SPN was verified by macroscopic quantification, immunohistochemistry and morphological analyses. Toxicity analyses were performed by evaluations of the kidney, liver, and spleen; analyses of hemogram and plasma levels of alanine aminotransferase, aspartate transaminase, urea, and creatinine; and DNA fragmentation and cell cycle activity of the bone marrow cells. Furthermore, we investigated the potential of the SPN formulation to cause hemolysis, activate the complement system, provoke an inflammatory response and change the conformation of the plasma proteins. Our results showed that the SPN reduced the area of the surface tumor nodules but not the total number of tumor nodules. The biochemical and hematological findings were suggestive of the low systemic toxicity of the SPN formulation. The surface properties of the selol nanocapsules point to characteristics that are consistent with the treatment of the tumors in vivo: low hemolytic activity, weak inflammatory reaction with no activation of the complement system, and mild or absent conformational changes of the plasma proteins. In conclusion, this report suggests that the SPN formulation investigated herein exhibits anti-tumoral effects against lung adenocarcinoma in vivo and is associated with low systemic toxicity and high biocompatibility.

Selol nanocapsules with a poly(methyl vinyl ether-co-maleic anhydride) shell conjugated to doxorubicin for combinatorial chemotherapy against murine breast adenocarcinoma in vivo

“…The main objective of this study was to investigate the antitumour improvement of a nanocapsule containing both selol and DOX as chemotherapeutic agents. The antitumour effect of a similar nanocapsule containing selol was previously observed by our research group [12]. In addition, the intracellular co-delivery of these molecules and the enhanced in vitro cytotoxicity achieved with selol and DOX combined were also demonstrated by our research group in 4T1 cancer cells [5].…”

“…Muehlmann et al [9] developed a nanoparticle consisting of a copolymer (PVM/MA) sphere used to immobilize a photosensitizer for breast cancer photodynamic therapy [10]. De Souza et al [11] developed nanocapsules with a core of selol, which is an oily mixture of selenitetriacylglycerides, and a shell of PVM/MA [11,12]. Next, Ganassin et al [5] combined DOX and selol in a similar PVM/MA-shelled nanocapsule (NCS-DOX), which was shown to co-deliver the loaded agents into mammary adenocarcinoma 4T1 cancer cells, as observed in in vitro experiments.…”

Protective Effects of Selol Against Sodium Nitroprusside-Induced Cell Death and Oxidative Stress in PC12 Cells

“…PC12 cells serve as a common model for the investigation of neurotoxic effects of stress [38] as well as neuroprotection induced by candidate drugs [39]. Selenium can be either pro- or antioxidant in various circumstances [29, 40] and may thus be either neuroprotective or cytotoxic [41]. In the present study we demonstrate that Selol potently inhibits SNP-induced dopaminergic PC12 cell death.…”

Nanocapsules for the co-delivery of selol and doxorubicin to breast adenocarcinoma 4T1 cells in vitro

“…Moreover, nanocarriers permit the combination of different drugs in one single compartment, a strategy indicated by some studies as capable of increasing the efficacy of the treatment and of reducing the probability of selection of resistant clones in the tumour tissue exposed to chemotherapy [7]. On that ground, selol has been speculated as a candidate for combinatory anticancer chemotherapy due to its cytostatic activity and chemotherapy-sensitizing property [8][9][10]. The selol is an oily mixture of different selenitetriacylglycerides, which contain organified selenium at its þ4 oxidation state.…”

“…Suchocki et al showed that the selol significantly reduced the viability of DOX-resistant leukaemia cells in vitro [8]. Moreover, de Souza et al showed that selol is cytostatic for lung adenocarcinoma A549 cells and urethane-induced lung cancer [9,10].…”