Advanced Therapeutics最新文献

Multifunctional drug delivery systems offer tremendous potential for improving antitumor efficacy, precise drug targeting, and controlled drug release in treating non-small cell lung cancer (NSCLC). In this study, the study develops a novel tumor-targeting ultrasound-responsive lipid nanoparticle (TUSL) platform capable of responding to external stimulation, enabling precise drug delivery with controlled release at the tumor site while minimizing systemic exposure and side effects. The TUSL platform is designed to carry doxorubicin (DOX) and tetrandrine (TET), specifically for drug-resistant NSCLC. The developed TUSL exhibits a nano sized spherical structure with a hydrodynamic size of 141.8 nm, accommodating anti-cancer drugs with loading capacities of 3.8% and 6.2% for TET and DOX, respectively. TUSL is engineered to target the epidermal growth factor receptor (EGFR) while demonstrating an ultrasound-triggered drug release profile. Through the generation of CO₂ bubbles upon ultrasound stimulation, the TUSL enhances DOX and TET internalization into tumor cells. In tumor-bearing mice, TUSL administration demonstrates a superior tumor accumulation with minimal off-target toxicity. The combined treatment with DOX and TET within TUSL exhibits synergistic effects, effectively inhibiting the growth of drug-resistant NSCLC tumors. These findings highlight the efficacy of the EGFR-targeted TUSL formulation in overcoming drug resistance and enhancing therapeutic outcomes in NSCLC.

The spinach-derived extracellular vesicles (Spinex) isolated from spinach efficiently suppressed lipid accumulation during adipocyte differentiation. The anti-obesity properties of Spinex are also demonstrated in a high-fat diet-induced mouse model. The research highlights Spinex as a promising natural biomaterial for combating obesity. More details can be found in article 2400150 by Won Jong Rhee and co-workers.

The tumor microenvironment of gliomas is fundamental to developing new therapeutic strategies. In article 2300442, Maria Kavallaris and co-workers explore the tumor environment of gliomas, focusing on the extracellular environment. The authors review 3D culture models as a tool to replicate this environment, providing valuable insights for therapeutic advancements. Cover image created with BioRender.com.

Sonodynamic therapy (SDT) is a minimally invasive cancer therapeutic modality that utilizes low-intensity ultrasound to activate sensitizers for the production of cytotoxic reactive oxygen species (ROS) and the site-specific ablation of tumors. Compared to conventional cancer treatments, SDT has no adverse side effects, has been shown to radically reduce tumor volume, and has the potential to raise antitumor immune response. Ever-increasing studies have demonstrated that nanotechnology can significantly enhance the efficacy of SDT against certain cancers and improve its therapeutic effects. Nanosystems are developed that can improve the intratumoral delivery and cellular uptake of sensitizers, can reduce intrinsic cancer defenses against ROS, can act synergistically for the production of ROS and can tackle cancer immune tolerance. In this review, the various strategies to enhance SDT performance with the assistance of nanotechnology, and the outstanding research outcomes, are discussed.

Neurological diseases (NDs) such as Alzheimer's disease, Parkinson's disease, ischemic strokes, spinal cord injuries, and other similar conditions that continue to pose a substantial health and economic burden on a global scale. It is crucial to tackle the difficulties provided by current medications due to the adverse effects and its immunological reactions to develop improved treatments for neurodegenerative illnesses. Gene therapy is currently being extensively used in preclinical and clinical studies for various diseases because of its ability to enhance the delivery and effectiveness of treatments. Various gene delivery techniques, including messenger RNA, small interfering RNA, antisense oligonucleotides, microRNA, CRISPR/Cas9 system, and plasmid DNA, have been created to address these difficulties. The goal of this study is to provide a clear overview of the pathophysiological underpinnings of NDs illnesses while also illuminating recent developments in gene delivery vector technologies. It goes over the main classifications of these vectors, their individual benefits and drawbacks, and their specific applications in the delivery of gene therapy.

MicroRNAs (miRs) play a critical role in modulating gene expression across biological processes, including cardiac aging and disease. As such, miRs have demonstrated therapeutic potential in several cardiac conditions. Efficient delivery of miR therapies to cardiac tissue is crucial for effective gene therapy and DNA-based nanocarriers (DNCs), based on Watson-Crick-Franklin highly specific base-pair recognition, have emerged as a promising, biocompatible alternative to viral-based methods. Here, DNCs designed to modulate miR levels as a potential treatment for cardiac dysfunction are presented. Specifically, the DNCs target miR-24-2, which inhibits SERCA2 gene. In humans, the reduction of SERCA2 activity is a hallmark of heart failure and is altered in cardiac aging. The assembled DNCs bearing anti-miR-24-2-5p sequences effectively restore intracellular levels of SERCA2 in a HEK293 cell model. The DNCs proper assembly is thoroughly verified, while their stability and miR-capture ability are demonstrated in vitro. The DNCs exhibit successful internalization into HEK293 and modest uptake into human cardiomyocytes. SERCA2 restoration by DNCs is significantly influenced by the miR-capture sequence layout, underscoring the importance of precise design for optimal biological outcomes. This study highlights the potential of DNCs in cardiac therapies, a previously unexplored avenue for addressing cardiac dysfunction.

Early diagnosis and treatment of hepatocellular carcinoma (HCC) remain major challenges. Significant efforts have been made to find new approaches to address these issues. Ferric-tannic nanoparticles (FTs) have emerged as promising tools for targeting the early phase of hepatocarcinogenesis due to their preferential accumulation in preneoplastic liver lesions. In this study, the therapeutic potential of FTs is demonstrated in early-stage hepatocarcinogenesis in rats. FTs inhibit the progression of early hepatocarcinogenesis, reducing hepatic nodules, preneoplastic foci (glutathione S-transferase placental (GST-P) form-positive foci), and HCC cell proliferation. The therapeutic effects of FTs appear to be mediated by inhibiting cell proliferation through the activation of immune responses. FTs show promise as novel immunomodulators or therapeutic agents for the treatment of early-stage HCC.

This review introduces nanomedicines and medical silks by addressing seminal and recent research within these fields. First, the successes of nanoparticles in improving the safety profiles and pharmacokinetic–pharmacodynamic properties are explored but also the concepts of threshold dosing and targeting of tumor-associated macrophages. Current barriers to systemic delivery of nanomedicines are detailed and methods to overcome these barriers and increase tumor targeting are evaluated, namely: tuning the nanomedicine size and surface charge for enhanced tumor accumulation and penetration; non-spherical nanomedicine morphologies for macrophage evasion and targeted delivery to endothelial cells; and, surface functionalization for stealth coatings and targeting receptor-mediated endocytosis. The advantages of using silk as a nanomedicine with reference to its structure, composition, biological performance, and formulation are discussed. While batch methods for silk processing enable the formation of nano to microparticles, continuous technology can overcome bottlenecks of the deployed engineering methods such as low throughput and poor reproducibility. Finally, the chemical modification of silk using homogeneous and heterogenous chemistries is assessed within the nanomedicine context. Overall, this review covers silk nanomedicines from first principles to carrier design and on to areas of future development.

Chronic wounds are one of the health challenges threatening human life. In these wounds, overexpression of some types of cytoskeletal actin-remodeling proteins including Flightless I (Flii) can often lead to severe skin scarring. Herein, arginine functionalized poly(β-amino ester)s are synthesized to develop polyplexes with alginate for delivery of Flii siRNA. This approach results in forming polyplexes with distinct features, such as tunable zeta potential, particle size, polydispersity, and arginine conjugation level. It is demonstrated that the uptake of arginine functionalized poly(β-amino ester)/alginate particles is composition-dependent for various cell types including J774.1 macrophages and BJ fibroblasts. Such polyplexes trigger nitric oxide release by macrophages enhancing the expression of anti-inflammatory genes while diminishing the expression of pro-inflammatory markers and demonstrating its immunomodulatory properties. Flii siRNA loaded particles provide condensed siRNA into the core-shell polyplex and exhibit controlled release of Flii siRNA over 24 h. The uptake rate of this polyplex by macrophages and fibroblasts is higher than that of a commercial gene carrier (Lipofectamine 2000), knocking down the in vitro Flii gene expression (1.3-fold). The increased BJ fibroblast proliferation and higher expression of collagen I (COL I) show the suitability of these polyplexes for wound healing.