Obesity-associated pathologies: Recent advances in stimuli-responsive nanocarriers for adipose tissue browning and beyond

Obesity is a chronic multifactorial disorder affecting more than 600 million people worldwide. It is initially caused by an imbalance between energy intake and consumption, and it is strongly correlated to many chronic and life-threatening disorders such as cardiovascular diseases, digestive diseases, colorectal cancer, and others. Obesity can be primarily managed via changing caloric consumption and including physical activity in the daily routine. Another solution is pharmacological therapies such as appetite suppressors and glucagon-like peptide-1 receptor agonists. Surgical intervention is also an available solution, but it is invasive, whereas changing caloric consumption or physical activity usually affords poor outcomes. Browning agents can convert WATs (white adipose tissues, energy-storing cells) into BATs (brown adipose tissues, energy-expending cells), which is an effective approach to reduce body weight. However, most of the available browning agents, either synthetic or natural, suffer from several drawbacks ranging from poor aqueous solubility to severe cardiovascular toxicity. As a result, there are more innovative approaches that can target obesity, such as passively targeted nanocarriers, depending on their lipophilicity or cationic nature. Actively targeted nanocarriers can target obesity depending on endothelial, adipocyte, or macrophage-based targeting. However, most recent research has transferred to develop more precise stimuli-responsive nanocarriers that can provide an on-demand drug release in response to different stimuli, either intrinsic or extrinsic. In this review, the most recent advances in stimuli-responsive nanocarriers in managing obesity and some of its related disorders including cardiovascular diseases and colorectal cancer, will be discussed.