Advanced Therapeutics最新文献

Advanced Therapeutics, Volume 5, Issue 8, 202200059

DOI: https://doi.org/10.1002/adtp.202200059

The following corrections to this paper should be noted.

There has been an accidental duplication that occurred when we edited Figure 4, we mistakenly edited Figure 3c into Figure 4f.

We apologize for this error. We now update the correct Figure 4 as follows.

Figure 4.

Adv. Therap. 2023, 2300143

Our NIH Program officer would like us to remove the funding association of grant R01DE31812 from the funding section of this PUBLISHED manuscript since it is not directly part of the Aims of the grant.

We apologize for this error.

In page 11, Acknowledgements section: “V.A.K. acknowledges support from the NIH NEI R15 EY029504, NIH NIDCR R01DE031812, NIH NIAMS R21AR079708, NIH NIAMS R01AR080895, NIH NIDCR R01DE029321, and NIH NCATS UL1TR003017, and the Undergraduate Research and Innovation program at NJIT” was incorrect. The text should read:

“V.A.K. acknowledges support from the NIH NEI R15 EY029504, NIH NIAMS R21AR079708, NIH NIAMS R01AR080895, NIH NIDCR R01DE029321, and NIH NCATS UL1TR003017, and the Undergraduate Research and Innovation program at NJIT”

We apologize for this error.

Alterations in the intestinal microenvironment, including increased levels of reactive oxygen species (ROS), abnormalities in intestinal mucosal immune regulation, and dysbiosis of the intestinal microbiota, are crucial to the development of inflammatory bowel disease (IBD). Herein, an oral colon-targeting Se-Probiotic@Alginate bead (BLSe) with ROS-scavenging ability and gut immune-microbiota microenvironment remodeling ability is developed using alginate as the primary outer shell encapsulated with probiotics Bacillus licheniformis (BL) and selenium nanoparticles stabilized by yeast glucan (SeNPs). In vitro studies have shown that SeNPs possess antioxidant activity and BLSe exhibits excellent stability in gastric fluids and are released in intestinal fluids. In vivo studies have also shown that BLSe significantly alleviated dextran sulphate sodium (DSS)-induced colitis in mice by inhibiting colon shortening, enhancing antioxidant activity, reducing pro-inflammatory cytokine secretion, and protecting the intestinal mucosal barrier. 16S ribosomal RNA sequencing shows that BLSe can remodel the composition of the gut microbiota by improving bacterial diversity and restoring the relative abundance of beneficial bacteria in the colon. Overall, this study advances a promising probiotic-based nanomedicine for managing IBD.

Extracellular vesicles (EVs) are membranous structures secreted by cells that play important roles in intercellular communication and material transport. Due to its excellent biocompatibility, lipophilicity, and homing properties, EVs have been used as a new generation of drug delivery systems for the diagnosis and treatment of tumors. Despite the potential clinical benefits of animal-derived extracellular vesicles (AEVs), their large-scale production remains sluggish due to the exorbitant cost of cell culture, challenging quality control measures, and limited production capabilities. This constraint significantly hinders their widespread clinical application. Plant-derived extracellular vesicles (PEVs) share similar functionalities with AEVs, yet they hold several advantages including a wide variety of source materials, cost-effectiveness, ease of preparation, enhanced safety, more stable physicochemical properties, and notable efficacy. These merits position PEVs as promising contenders with broad potential in the biomedical sector. This review will elucidate the advantages of PEVs, delineating their therapeutic mechanisms in cancer treatment, and explore the prospective applications of engineered PEVs as targeted delivery nano-system for drugs, microRNAs, small interfering RNAs, and beyond. The aim is to heighten researchers’ focus on PEVs and expedite the progression from fundamental research to the transformation of groundbreaking discoveries.

Phytochemicals are a diverse class of compounds found in various plant-based foods and beverages that have displayed the capacity to exert powerful anticancer effects through the induction of programed cell death (PCD) in malignancies. PCD is a sophisticated process that maintains in upholding tissue homeostasis and eliminating injured or neoplastic cells. Phytochemicals have shown the potential to induce PCD in malignant cells through various mechanisms, including modulation of cell signaling pathways, regulation of reactive oxygen species (ROS), and interaction with critical targets in cells such as DNA. Moreover, recent studies have suggested that nanomaterials loaded with phytochemicals may enhance cell death in tumors, which can also stimulate antitumor immunity. In this review, a comprehensive overview of the current understanding of the anticancer effects of phytochemicals and their potential as a promising approach to cancer therapy, is provided. The impacts of phytochemicals such as resveratrol, curcumin, apigenin, quercetin, and some approved plant-derived drugs, such as taxanes on the regulation of some types of PCD, including apoptosis, pyroptosis, anoikis, autophagic cell death, ferroptosis, and necroptosis, are discussed. The underlying mechanisms and the potential of nanomaterials loaded with phytochemicals to enhance PCD in tumors are also explained.

Cancer remains a persistent global health concern, representing a significant challenge in medical science and patient care. In this context, l-asparaginase has emerged as a promising therapeutic agent due to its unique ability to deplete circulating asparagine, thereby selectively targeting cancer cells. However, despite its potential, current formulations of l-asparaginase are not without limitations. Issues such as immunogenicity, short half-life, and variable efficacy present hurdles in its widespread clinical application. To overcome these hurdles, researchers are focusing on developing bio-better versions of l-asparaginase. These bio-betters aim to enhance stability, reduce immunogenicity, and optimize enzyme kinetics, thus improving treatment outcomes. This review critically assesses the current landscape of l-asparaginase bio-betters, offering insights into ongoing formulations and advancements, optimization strategies, and future bio-engineering frontiers. It discusses modifications to enhance therapeutic properties and explores innovative approaches like in-silico enzyme engineering and artificial intelligence, highlighting their potential to improve the therapeutic profile of l-asparaginase. Challenges and debates surrounding the l-asparaginase mechanism are also addressed. By addressing current challenges and outlining future directions, this review aims to contribute to the advancement of anti-cancer therapeutics, particularly in the context of l-asparaginase bio-better research.

Neogambogic acid (NGA) is a potent antitumor drug but faces significant obstacles to clinical application, including extremely poor water solubility and systemic toxicity. To overcome these obstacles, a newly developed nanoparticle, adiposome, that consists of a neutral lipid core wrapped with a phospholipid-monolayer membrane, is utilized for the delivery of NGA. In this study, NGA-loaded cationic adiposomes (NGA-C-ADs) are constructed in which NGA is encapsulated within the neutral lipid core and surrounded by phospholipids and a cationic lipid. The concentration of NGA in NGA-C-ADs achieved is as high as 1.0 mg mL⁻¹, which is 2 000-fold higher than in aqueous buffer alone. Moreover, in vitro cell tests revealed that NGA-C-ADs exhibited higher cytotoxicity against various cancer cell lines compared to free NGA. In addition, in vivo anti-tumor animal studies demonstrate that NGA-C-ADs effectively inhibit tumor growth in subcutaneous CT26 tumor-bearing mice and also suppress chemically-induced hepatocellular carcinoma without obvious toxicity to major organs. These findings suggest that NGA-C-ADs hold promise as a potential treatment for multiple cancers.

Male patients have a higher risk of cardiotoxicity following doxorubicin (DOX) treatment than female patients. However, how this difference occurs at the transcriptome level remains unclear, and the mechanisms underlying these differences are understudied. This study aimed to describe the transcriptional patterns of males and females after DOX treatment and explore the possible mechanisms of sexual differences in DOX-induced cardiotoxicity. Following DOX treatment, male mice exhibit more severe heart damage than female mice. Transcriptome analysis of mice with and without DOX treatment showed that differentially expressed genes (DEGs) are significantly different between males and females. The majority of DEGs are sex-specific, and more DEGs are identified in males than females. A number of genes, including the oxidation-related genes Gdf15 and Rbm3, exhibited altered expression either in males or females. Some other genes, including the ferroptosis-related gene Cd74, changed their expression levels in both sexes, but at different scales. Biochemical experiments suggested that cardiomyocyte oxidation and ferroptosis may contribute to the sexual dimorphism of DOX-induced cardiotoxicity. In summary, this study shows that, after exposure to DOX, males and females respond differently regarding the expression of hundreds of genes, including Gdf15, Rbm3, and Cd74, possibly explaining the sexual differences in DOX-induced cardiotoxicity.