Current Pharmaceutical Design - Volume 25, Issue 46, 2019

Background: Cancer causes millions of deaths and huge economic losses every year. The currently practiced methods for cancer therapy have many defects, such as side effects, low curate rate, and discomfort for patients. Objective: Herein, we summarize the applications of gold nanorods (AuNRs) in cancer therapy based on their photothermal effect-the conversion of light into local heat under irradiation. Methods: The recent advances in the synthesis and regulation of AuNRs, and facile surface functionalization further facilitate their use in cancer treatment. For cancer therapy, AuNRs need to be modified or coated with biocompatible molecules (e.g. polyethylene glycol) and materials (e.g. silicon) to reduce the cytotoxicity and increase their biocompatibility, stability, and retention time in the bloodstream. The accumulation of AuNRs in cancerous cells and tissues is due to the high leakage in tumors or the specific interaction between the cell surface and functional molecules on AuNRs such as antibodies, aptamers, and receptors. Results: AuNRs are employed not only as therapeutics to ablate tumors solely based on the heat produced under laser that could denature protein and activate the apoptotic pathway, but also as synergistic therapies combined with photodynamic therapy, chemotherapy, and gene therapy to kill cancer more efficiently. More importantly, other materials like TiO2, graphene oxide, and silicon, etc. are incorporated on the AuNR surface for multimodal cancer treatment with high drug loadings and improved cancer-killing efficiency. To highlight their applications in cancer treatment, examples of therapeutic effects both in vitro and in vivo are presented. Conclusion: AuNRs have potential applications for clinical cancer therapy.

The prevention and treatment of various infections caused by microbes through antibiotics are becoming less effective due to antimicrobial resistance. Researches are focused on antimicrobial nanomaterials to inhibit bacterial growth and destroy the cells, to replace conventional antibiotics. Recently, carbon dots (C-Dots) become attractive candidates for a wide range of applications, including the detection and treatment of pathogens. In addition to low toxicity, ease of synthesis and functionalization, and high biocompatibility, C-Dots show excellent optical properties such as multi-emission, high brightness, and photostability. C-Dots have shown great potential in various fields, such as biosensing, nanomedicine, photo-catalysis, and bioimaging. This review focuses on the origin and synthesis of various C-Dots with special emphasis on bacterial detection, the antibacterial effect of CDots, and their mechanism.

Gold nanoparticles with special surface plasmon resonance have been widely used in sensing and therapy because of their easy preparation, unique optical properties, excellent biocompatibility, etc. The applications of gold nanoparticles in chemo/biosensing, imaging, and therapy reported in 2016-2019, are summarized in this review. Regarding the gold nanoparticle-based sensing or imaging, sensing mechanisms and strategies are provided to illustrate the concepts for designing sensitive and selective detection platforms. Gold nanoparticlemediated therapy is introduced by surface plasmon resonance-based therapy and delivery-based therapy. Beyond the sole therapeutic system, platforms through synergistic therapy are also discussed. In the end, discussion of the challenges and future trends of gold nanoparticle-based sensing and therapy systems is described.

Acute lung injury/acute respiratory distress syndrome is a common clinical illness with high morbidity and mortality, which is still one of the medical problems urgently needed to be solved. Alveolar type 2 epithelial cells are an important component of lung epithelial cells and as a kind of stem cells, they can proliferate and differentiate into alveolar type 1 epithelial cells, thus contributing to lung epithelial repairment. In addition, they synthesize and secrete all components of the surfactant that regulates alveolar surface tension in the lungs. Moreover, alveolar type 2 epithelial cells play an active role in enhancing alveolar fluid clearance and reducing lung inflammation. In recent years, as more advanced approaches appear in the field of stem and progenitor cells in the lung, many preclinical studies have shown that the cell therapy of alveolar type 2 epithelial cells has great potential effects for acute lung injury/acute respiratory distress syndrome. We reviewed the recent progress on the mechanisms of alveolar type 2 epithelial cells involved in the damaged lung repairment, aiming to explore the possible therapeutic targets in acute lung injury/acute respiratory distress syndrome.

Bortezomib (VELCADE®) is a boronate peptide and first-in-class proteasome inhibitor serving an important role in degenerating several intracellular proteins. It is a reversible inhibitor of the 26S proteasome, with antitumor activity and antiproliferative properties. This agent principally exerts its antineoplastic effects by inhibiting key players in the nuclear factor ΚB (NFΚB) pathway involved in cell proliferation, apoptosis, and angiogenesis. This medication is used in the management of multiple myeloma. However, more recently, it has been used as a therapeutic option for mantle cell lymphoma. While promising, bortezomib has limited clinical applications due to its adverse effects (e.g., hematotoxicity and peripheral neuropathy) and low effectiveness in solid tumors resulting from its poor penetration into such masses and suboptimal pharmacokinetic parameters. Other limitations to bortezomib include its low chemical stability and bioavailability, which can be overcome by using nanoparticles for its delivery. Nanoparticle delivery systems can facilitate the targeted delivery of chemotherapeutic agents in high doses to the target site, while sparing healthy tissues. Therefore, this drug delivery system has provided a solution to circumvent the limitations faced with the delivery of traditional cancer chemotherapeutic agents. Our aim in this review was to describe polymer-based nanocarriers that can be used for the delivery of bortezomib in cancer chemotherapy.

Inflammatory bowel disease (IBD) is a chronic, elusive disorder resulting in relapsing inflammation of intestine with incompletely elucidated etiology, whose two representative forms are ulcerative colitis (UC) and Crohn’s disease (CD). Accumulating researches have revealed that the individual genetic susceptibility, environmental risk elements, intestinal microbial flora, as well as innate and adaptive immune system are implicated in the pathogenesis and development of IBD. Despite remarkable progression of IBD therapy has been achieved by chemical drugs and biological therapies such as aminosalicylates, corticosteroids, antibiotics, anti-tumor necrosis factor (TNF)-α, anti-integrin agents, etc., healing outcome still cannot be obtained, along with inevitable side effects. Consequently, a variety of researches have focused on exploring new therapies, and found that natural products (NPs) isolated from herbs or plants may serve as promising therapeutic agents for IBD through antiinflammatory, anti-oxidant, anti-fibrotic and anti-apoptotic effects, which implicates the modulation on nucleotide- binding domain (NOD) like receptor protein (NLRP) 3 inflammasome, gut microbiota, intestinal microvascular endothelial cells, intestinal epithelia, immune system, etc. In the present review, we will summarize the research development of IBD pathogenesis and current mainstream therapy, as well as the therapeutic potential and intrinsic mechanisms of NPs in IBD.

Psoriasis is a chronic inflammatory disease affecting over 8 million Americans. Importantly, patients with psoriasis are at an increased risk of developing atherosclerosis, coronary artery disease, and myocardial infarctions. Several studies have suggested that psoriasis may be an independent risk factor for cardiovascular disease given their shared inflammatory properties and pathogenic similarities. Epicardial fat is also linked to cardiovascular disease and may be an independent risk factor for atherosclerosis. It has been proposed that measuring epicardial fat tissue may serve as a useful subclinical measure of cardiovascular disease in psoriasis patients. Echocardiography has been increasingly adopted as an accurate, minimally invasive, and cost-effective measure of determining the volume and thickness of epicardial fat. Using echocardiographic measures of epicardial fat thickness as a marker of cardiovascular disease and therapeutic target in psoriasis patients may provide clinicians with a means to better manage and hopefully prevent deleterious downstream effects.

Background: Anthocyanins are a type of flavonoids that are natural water soluble glycosidic pigments with efficacious anti-cancer effects, which have good biological activity against many cancers including colorectal cancer (CRC). However, the exact molecular mechanism used by anthocyanins against cancer is unclear; it is also unclear what a reasonable dosage might be for their use against colorectal cancer. Methods: Western blotting, immunohistochemistry, MTT assay, xenograft model, and hematoxylin-eosin (HE) staining were used to perform the experiments. Results: Compared with the control group, anthocyanins could significantly inhibit the cell viability and proliferation and promote the apoptosis of human colon cancer HT29 cells. Furthermore, anthocyanins reduced tumor weight and volume in a colon tumor mouse model and downregulated the expression of PI3K protein, inhibited AKT expression and phosphorylation, decreased the Bcl-2 and Bax ratio and reduced survivin protein expression in the tumor tissue. Conclusion: Anthocyanins promoted apoptosis of CRC cells and inhibited colon cancer growth of xenografted tumors. Mechanistically, anthocyanins enhanced the Bcl-2/Bax and caspase-dependent apoptotic pathways through targeting the PI3K/AKT/survivin pathway, resulting in impairment of growth of CRC.