Targeted biological contrast agents are emerging as promising candidates in the field of cancer theragnostics. Herein, we report an ambient temperature synthesis of a nanosized, antibody functionalized lanthanide doped CaF2 biolabel and demonstrate in vitro its potential for cancer cell targeting efficacy and specificity. Monodispersed citrate stabilized lanthanide (Eu3+) doped CaF2 nanoparticles with size ∼25 nm, exhibiting strong fluorescent emission at 612 nm, were prepared using an aqueous wet chemical route at room temperature. Biofunctionalization of the fluorescent nanoparticles using an anti-EGFR antibody through EDC–NHS coupling chemistry enabled targeting of EGFR over-expressing cells. The nanobioconjugates showed preferential binding to EGFR+ve oral epithelial carcinoma cells (KB) and human epidermoid carcinoma cells (A431) with no accumulation onto EGFR−ve non-cancerous NIH 3T3 cells. The fluorescence was maintained after the bioconjugation as well as after attachment to the cancer cells, demonstrating their potential as targeted biolabels. Cytotoxicity evaluation with several cancerous (A431, KB) and non-cancerous (NIH 3T3, L929) cell lines revealed no toxicity at concentrations up to 1 mM. Thus, the fluorescence characteristics and biocompatibility, coupled with the molecular receptor targeting capability, suggest the potential use of CaF2 in the field of bioimaging.
Numerous factors need to be considered to develop a nanodrug delivery system that is biocompatible, non-toxic, easy to synthesize, cost-effective, and feasible for scale up over and above their therapeutic efficacy. With regards to this, worldwide, exosomes, which are nano-sized vesicles obtained from mammalian cells, are being explored as a biomimetic drug delivery system that has superior biocompatibility and high translational capability. However, the economics of undertaking large-scale mammalian culture to derive exosomal vesicles for translation seems to be challenging and unfeasible. Recently, Bacterial Membrane Vesicles (BMVs) derived from bacteria are being explored as a viable alternative as biomimetic drug delivery systems that can be manufactured relatively easily at much lower costs at a large scale. Until now, BMVs have been investigated extensively as successful immunomodulating agents, but their capability as drug delivery systems remains to be explored in detail. In this review, the use of BMVs as suitable cargo delivery vehicles is discussed with focus on their use for in vivo treatment of cancer and bacterial infections reported thus far. Additionally, the different types of BMVs, factors affecting their synthesis and different cargo loading techniques used in BMVs are also discussed.
17 August 2017 in ACS Applied Materials & Interfaces
The hypothalamus plays important roles in maintaining overall body homeostasis and energy balance. Disruption of its normal functioning has been associated with the onset of various metabolic disorders in the body that arise from several genetic, immunological, and environmental factors or their combination. To combat this, developing treatment strategies that modulate the activity of the hypothalamus could be advantageous. Here, understanding the hypothalamus’s complex structure and function within the context of regulation of energy balance is important to identify treatment targets and to explore opportunities to modulate key metabolic pathways. Moreover, the unique sensitive position of the hypothalamus in the brain necessitates that treatment strategies that are developed are highly effective and specific, and do not cause any untoward effects at neighboring regions of the brain. This is further complicated by its protection through the blood-brain barrier (BBB) that highly regulates the entry of materials from the periphery, allowing entry of molecules only under specific conditions. In this regard, advanced multifunctional nanoparticulate drug-delivery systems can be of benefit as they have been explored for brain specific delivery. For this, nanoparticle chemistry, specific ligand expression, BBB penetration capability, biocompatibility, and immunogenicity among other physicochemical properties are important parameters that govern brain specific delivery. In this review, the role of hypothalamus in regulating energy metabolism, its structure and function and the effect of dysfunction on the onset of metabolic disorders are summarized. Furthermore, the use of nanoparticles for brain targeting and hypothalamic regulation, such as small extracellular vesicles targeting AMP-activated protein kinase (AMPK), along with the future of nanoparticle-based modulation of the hypothalamus is also discussed.