Apoptosis signaling pathways, drug resistance, and metastasis are important targets to develop new cancer treatments. We developed cholesterol-coated Poly(d,l-Lactide-co-Glycolic Acid) (PLGA) nanoparticles for effective encapsulation and delivery of retinoic acid and oxaliplatin to analyze their antitumor activity in colorectal cancer. The cell viability and proliferation of tumoral cells lines (CT-26 and SW-480) decreased when compared to control in vitro after treatment with the nanoparticles. In addition, apoptosis of CT-26 cells increased. Importantly, cytoprotection of nontumor cells was detected. Expression of pro-apoptotic proteins was upregulated, while anti-apoptotic proteins were downregulated either in vitro or in vivo. In addition, drug resistance and metastasis factors were downregulated in vivo. Human colorectal tumors that highly expressed BCL-2 and Ki-67 had a greater tendency towards death within 60 months. Our results show that loading oxaliplatin combined with retinoic acid and cholesterol in a nanoparticle formulation enables determination of optimal antitumor activity and subsequent treatment efficacy.

Nanotechnology is a promising tool for the treatment of cancer. In the past decades, major steps have been made to bring nanotechnology into the clinic in the form of nanoparticle-based drug delivery systems. The great hope of drug delivery systems is to reduce the side effects of chemotherapeutics while simultaneously increasing the efficiency of the therapy. An increased treatment efficiency would greatly benefit the quality of life as well as the life expectancy of cancer patients. However, besides its many advantages, nanomedicines have to face several challenges and hurdles before they can be used for the effective treatment of tumors. Here, we give an overview of the hallmarks of cancer, especially colorectal cancer, and discuss biological barriers as well as how drug delivery systems can be utilized for the effective treatment of tumors and metastases.

Purpose: Bioactive molecules are relevant to fight cancer and associated conditions. Quinoxaline is a privileged N-heterocycle, notably as anticancer agents. Herein, we report the evaluation of the quinoxaline derivatives DEQX and OAQX as anticancer agents, as well as in function of their anti-inflammatory and analgesic activities. Methods: Quinoxalines were synthesized and tested as anticancer agents based on cell viability and Annexin V-FITC apoptosis. Anti-inflammatory activity was evaluated from mouse carrageenan peritonitis and levels of interleukin (IL)-1β and tumor necrosis factor (TNF)-alfa for enzyme-linked immunosorbent assay. Hot-plate and acetic acid-induced writing test were employed to investigate analgesia. Results: Both reduced the Ht-29 cell viability in a dependent-concentration manner (p < 0.001). Total apoptosis was detected for cells treated with 12.5 and 25 µg/mL of both the compounds for 24 and 48 h (all doses, p < 0.0001). DEQX (all doses, p < 0.01) and OAQX (all doses, p < 0.001) acted in leukocyte migration and decreased the IL-1β and TNF-β levels (p < 0.05). DEQX (all doses, p < 0.05) and OAQX (5mg/kg, p < 0.001) showed peripheral analgesic effect. Conclusions: In-vitro and in-vivo results suggest that these quinoxalines are promising for application in pharmacological area due to their anticancer, anti-inflammatory, and peripheric analgesia.