Glutathione-Responsive Prodrug Nanoparticles for Effective Drug Delivery and Cancer Therapy

Abstract

Spurred by recent progress in medicinal chemistry, numerous lead compounds have sprung up in the past few years, although the majority are hindered by hydrophobicity, which greatly challenges druggability. In an effort to assess the potential of platinum (Pt) candidates, the nanosizing approach to alter the pharmacology of hydrophobic Pt(IV) prodrugs in discovery and development settings is described. The construction of a self-assembled nanoparticle (NP) platform, composed of amphiphilic lipid-polyethylene glycol (PEG) for effective delivery of Pt(IV) prodrugs capable of resisting thiol-mediated detoxification through a glutathione (GSH)-exhausting effect, offers a *

Preparation of Cholesteryl-Modified Aminated Pullulan Nanoparticles to Evaluate Nanoparticle of Hydrophobic Degree on Drug Release and Cytotoxicity

“…Therefore, many studies of polymer synthesis have examined the formation properties and function of NPs by hydrophobic substitution. Some of these studies show that changing the grafting density of the hydrophobic-substituted base can change the size, shape, elasticity, solubility, and stability of NPs [7][8][9][10].…”

“…The effect of hydrophobic substitution degree on some properties of NPs will affect the function of the NPs. The greater the degree of hydrophobic substitution, the smaller the particle size of self-assembled NPs [10]. The size of NPs plays a decisive role in the accuracy of their passive targeted delivery of anticancer drugs: 50 to 200 nm NPs can make better use of the high permeability of blood vessels near the tumor and enhanced permeability retention (EPR) effect of passive targeting of tumor sites [11]; therefore, the effect of hydrophobic substitution on the size of NPs is of great significance.…”

“…The hydrophobicity of NPs can be changed by changing the substitution degree of cholesterol, which changes the size and drug loading and release of NPs [24]. However, because of the large surface area and high surface activity, NPs can easily agglomerate, which will have adverse effects [10,25]. Because of electrostatic repulsion, charged NPs are not easily aggregated as compared with uncharged NPs.…”

Enhanced cytotoxicity of a redox-sensitive hyaluronic acid-based nanomedicine toward different oncocytes via various internalization mechanisms

“…Biological response signals in the tumor microenvironment include extracellular and intracellular pH changes or specific enzymes, a strong reduction environment in the tumor cells and other signals (Tang et al, 2018;Uthaman et al, 2018). The glutathione (GSH) level in tumor cells is up to 2-20 mM, which is 4-10 times higher than that in normal cells and nearly 1000 times than that in the extracellular fluid and blood Ling et al, 2019). Therefore, a relatively strong reduction environment in tumor cells could be a promising bio-signal for smart drug delivery.…”

An Enzyme‐Responsive Prodrug with Inflammation‐Triggered Therapeutic Drug Release Characteristics

“…In addition, polymeric microspheres or nanoparticles can also be fabricated from the mixture of the prodrug and polymers. [42]…”