Vascular targeted nanotherapeutic approach for obesity treatment

Abstract

Obesity is a global epidemic that poses a serious health concern due to it being a risk factor for life-threatening chronic diseases, such as type 2 diabetes, cancer, and cardiovascular diseases. Pharmacotherapy remains the mainstay for the management of obesity; however, its usefulness is limited due to poor drug efficacy, non-specificity and toxic side effects. Therefore, novel approaches that could provide insights into obesity and obesity-associated diseases as well as development of novel anti-obesity treatment modalities or improvement on the existing drugs are necessary. While the ideal treatment of obesity should involve early intervention in susceptible individuals, targeted nanotherapy potentially provides a fresh perspective that might be better than the current conventional therapies. Independent studies have shown improved drug efficacy by using prohibitin (PHB)-targeted therapy in obese rodents and non-human primates, thus providing a proof of concept that targeted nanotherapy can be a feasible treatment for obesity. This review presents a brief global survey of obesity, its impact on human health, its current treatment and their limitations, and the role of angiogenesis and PHB in the development of obesity. Finally, the role and potential use of nanotechnology coupled with targeted drug delivery in the treatment of obesity are discussed.

7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity

“…This is associated with important modifications of the lipid profile and with organelle dysfunction (mitochondria, lysosome, peroxisome) [1]. As increased levels of 7KC and 7β-OHC are associated in major diseases such as age-related diseases (cardiovascular diseases, neurodegeneration, eye disorders, osteoporosis and some cancers) and chronic diseases (bowel diseases) [2,3], there is a need to better understand the biological activities of these molecules not only in vitro but also in vivo in order i) to identify pharmacological targets, and ii) to identify natural and synthetic compounds capable of counteracting 7KC-and 7β-OHC-induced side effects, as well as iii) to develop innovative therapeutic strategies (targeted nanotherapies [4], bioremediation [5,6]). To overcome deficits in animal models whose results are sometimes difficult to transfer to humans, the development of alternative methods ("Lab on a Chip" / "Body on Chip" / organoids), perhaps combined with the use of inducible pluripotent stem cells (iPSCs), are promising integrative approaches.…”

Nanotechnology advances towards development of targeted-treatment for obesity

“…PHB has shown potential as a WAT vascular marker [11]. Although the protein is expressed in various cellular compartments [56, 57], it is highly expressed as a cell surface receptor in the vasculature of the WAT in diet-induced animal models of obesity and humans [11, 13–15]. As such, PHB can be used for targeted delivery of cytotoxic agents to vascular endothelial cells inhibiting angiogenesis in the WATs and reverse obesity (Fig.…”

“…As such, PHB can be used for targeted delivery of cytotoxic agents to vascular endothelial cells inhibiting angiogenesis in the WATs and reverse obesity (Fig. 2) [11, 57]. Molecules that bind to PHB with high specificity have been identified through phage display [11, 57], among them the CKGGRAKDC peptide has been used in various obesity models [11, 13–15].…”

“…2) [11, 57]. Molecules that bind to PHB with high specificity have been identified through phage display [11, 57], among them the CKGGRAKDC peptide has been used in various obesity models [11, 13–15]. This peptide will be referred to as adipose homing peptide (AHP) [15].…”

“…To overcome the protein degradation, immune response and dosage hurdles, nanotechnology-based strategies were developed. Nanotechnology is defined as the development of materials with a size of ≤ 100 nm [57, 58]. Various types of nanoparticles (NPs) have been developed for a number of applications in environmental, energy, water and medical sectors.…”