Over the past decade, more interests have been aroused in engineering protein-based nanoformulations for cancer treatment. This excitement originates from the success of FDA approved Abraxane (Albumin-based paclitaxel nanoparticles) in 2005. The new generation of biocompatible endogenous protein-based nanoformulations is currently constructed through delivering cancer therapeutic and diagnostic agents simultaneously, as named potential theranostics. Protein nanoformulations are commonly incorporated with dyes, contrast agents, drug payloads or inorganic nanoclusters, serving as imaging-guided combinatorial cancer therapeutics. Employing the nature identity of proteins, the theranostics, escape the clearance by reticuloendothelial cells and have a long blood circulation time. The nanoscale sizet allows them to be penetrated deeply into tumor tissues. In addition, stimuli release and targeted molecules are incorporated to improve the delivery efficiency. The ongoing advancement of protein-based nanoformulations for cancer theranostics in recent 5 years is reviewed in this paper. Fine-designed nanoformulations based on albumin, ferritin, gelatin, and transferrin are highlighted from the literature. Finally, the current challenges are identified in translating protein-based nanoformulations from laboratory to clinical trials.
Tubulin inhibitors are effective anticancer agents, however, there are many limitations to the use of available tubulin inhibitors in the clinic, such as multidrug resistance, severe side-effects, and generally poor bioavailability. Thus, there is a constant need to search for novel tubulin inhibitors that can overcome these limitations. Natural product and privileged structures targeting tubulin have promoted the discovery and optimization of tubulin inhibitors. This review will focus on novel tubulin inhibitors derived from natural products and privileged structures targeting the colchicine binding site on tubulin.
6 February 2018 in Journal of Materials Chemistry B
An elevated reactive oxygen species (ROS) level leads to cellular oxidative stress, which has long been associated with diseases, such as cancer. Thus, the understanding and appropriate manipulation of cellular oxidative stress are needed for disease treatment. It has been reported that nanoparticles induce oxidative stress in human cells through different pathways. However, how the physicochemical properties of nanoparticles perturb cellular oxidative stress remains unclear. In this paper, we explored the effects of the positive/negative charge density and hydrophobicity of gold nanoparticles (GNPs) on the induction of oxidative stress and related mechanisms. In multiple human cell lines, we found that only the positive charge density and hydrophobicity of nanoparticles were correlated with the induction of cellular oxidative stress. Hydrophobic nanoparticles generated oxidative stress mainly through NADPH oxidase activation while positively charged nanoparticles generated it through perturbations of the mitochondria and modulation of intracellular Ca2+ concentration. Furthermore, nanoparticle-induced oxidative stress sensitized paclitaxel-induced cancer cell killing by 200%. These findings provided unequivocal structural parameters for the design of future nanomedicine and biocompatible nanocarriers.
In recent years, the number of patients diagnosed with cancer has been soaring. Therefore, the design, development, and implementation of new approaches for the diagnosis and therapy of different types of cancers have attracted an increasing amount of attention. To date, different methods have been used for cancer diagnosis and therapy with main drawbacks in terms of severe side effects, e.g., damage to healthy cells, development of drug resistance and tumor recurrence. Therefore, there is an urgent need for the introduction and application of innovative methods. Covalent organic frameworks (COFs) are versatile materials with excellent properties in terms of biocompatibility, porous and crystalline structure, and easy functionalization. The porous structure and organic monomers in COFs allow them to load different therapeutic drugs and/or functional species efficiently. These promising properties make COFs ideal candidates for medical application, especially in cancer diagnosis and therapy. To date, many studies have focused on the design and synthesis of novel COFs while their application as diagnostic and therapeutic materials remains less understood. In this review, different synthesis and functionalization approaches of COFs were summarized. In particular, cancer diagnosis and therapy based on COFs were investigated and the advantages and limitations of each method were discussed. Most importantly, the mechanism for cancer therapy of COFs and fundamental challenges and perspectives for the application of COFs in cancer theranostics were assessed.
The escalating frequency of thallium (Tl) contamination incidents amplifies its environmental risk. However, the potential risk of Tl to aquatic organisms, especially across varying developmental stages, remains poorly understood. In this study, we employed zebrafish as a representative model organism and exposed zebrafish embryos and larvae at distinct developmental periods (specifically, 6 h postfertilization (hpf) and 72 hpf) to low concentrations of Tl(I) (0.25 and 0.50 mg/L). The exposure was performed for a short duration of 24 h, followed by a 96 h depuration period. Our results revealed that Tl(I) exerted disparate biological effects on zebrafish at different developmental stages. Embryos exhibited negligible uptake of Tl(I), whereas larvae showed a significant accumulation of Tl(I) and struggled with its rapid elimination. Notably, Tl(I) was able to permeate the blood-brain barrier, thereby posing a risk to the nervous system. Transcriptomic analysis indicated that Tl(I) triggered distinct toxicological pathways in embryos and larvae. It mainly interfered with metabolic processes in embryos, while in larvae, it mainly disrupted intracellular ion homeostasis, both consequently provoking neurotoxicity. This emphasizes that the multifaceted nature of Tl(I) toxicity depends on the developmental stages of the organism. This study clearly shows that the bioeffects of Tl are intricately related to the developmental stage of zebrafish, offering a valuable perspective for the pollutant toxicity assessment.