Enhancing Targeted Therapy in Breast Cancer by Ultrasound-Responsive Nanocarriers.

Currently, the response to cancer treatments is highly variable, and severe side effects and toxicity are experienced by patients receiving high doses of chemotherapy, such as those diagnosed with triple-negative breast cancer. The main goal of researchers and clinicians is to develop new effective treatments that will be able to specifically target and kill tumor cells by employing the minimum doses of drugs exerting a therapeutic effect. Despite the development of new formulations that overall can increase the drugs' pharmacokinetics, and that are specifically designed to bind overexpressed molecules on cancer cells and achieve active targeting of the tumor, the desired clinical outcome has not been reached yet. In this review, we will discuss the current classification and standard of care for breast cancer, the application of nanomedicine, and ultrasound-responsive biocompatible carriers (micro/nanobubbles, liposomes, micelles, polymeric nanoparticles, and nanodroplets/nanoemulsions) employed in preclinical studies to target and enhance the delivery of drugs and genes to breast cancer.

Novel Disinfection Byproducts Formed from the Pharmaceutical Gemfibrozil Are Bioaccumulative and Elicit Increased Toxicity Relative to the Parent Compound in Marine Polychaetes (Neanthes arenaceodentata).

Formation of halogenated disinfection byproducts (DBPs) from pharmaceutically active compounds has been observed in water supply systems following wastewater chlorination. Although research has been limited thus far, several studies have shown that halogenated DBPs may elicit increased toxicity compared to their parent compounds. For example, the lipid regulator gemfibrozil has been shown to form chlorogemfibrozil (Cl-gemfibrozil) and bromogemfibrozil (Br-gemfibrozil) following chlorination, which are more potent antiandrogens in male Japanese medaka (Oryzias latipes) compared to their parent compounds. In the present study, we aimed to characterize the bioaccumulative ability of halogenated gemfibrozil DBPs in marine polychaetes via chronic sediment exposures and, consequently, to assess the chronic and acute toxicity of halogenated gemfibrozil DBPs through sediment (in vivo) and aqueous (in vivo and in silico) toxicity evaluations. Following 28 day sediment exposures, Cl-gemfibrozil and Br-gemfibrozil bioaccumulated within Neanthes arenaceodentata, with both compounds reducing survival and growth. The biota-sediment accumulation factors determined for Cl-gemfibrozil and Br-gemfibrozil were 2.59 and 6.86, respectively. Furthermore, aqueous 96 h toxicity tests with N. arenaceodentata indicated that gemfibrozil DBPs elicited increased toxicity compared to the parent compound. While gemfibrozil had an acute LC50 value of 469.85 ± 0.096 mg/L, Cl-gemfibrozil and Br-gemfibrozil had LC50 values of 12.34 ± 0.085 and 9.54 ± 0.086 mg/L, respectively. Although acute toxicity is relatively low, our results indicate that halogenated gemfibrozil DBPs are bioaccumulative and may elicit effects in apex food web organisms prone to accumulation following lifelong exposures.