Advanced Therapeutics最新文献

Oxidative stress, a key driver of heart failure progression, is exacerbated by 5-oxoproline accumulation due to reduced 5-oxoprolinase (OPLAH) activity. While enhancing OPLAH function represents a promising therapeutic strategy, effective intracellular delivery of activity-modulating compounds remains highly challenging. Here, we develop a comprehensive approach combining high-throughput screening technology and advanced nanocarrier design to address effective intracellular delivery. Through the screening of an FDA-approved compound library, we identify adenosine 5′-monophosphate (AMP) as a novel OPLAH activator, demonstrating direct modulation through thermal shift assay and a dose-dependent activation via liquid chromatography mass spectrometry (LC-MS/MS) analysis. To overcome the AMP's limited cellular permeability, we engineer acetalated dextran spermine-modified nanoparticles (AcDXSp-NPs) with optimized physicochemical properties for efficient intracellular delivery. The AMP-loaded nanoparticles exhibit a high encapsulation efficiency (>70%) and controlled pH-dependent release. In cell-based studies, these nanocarriers significantly enhance OPLAH activity, evidenced by a >50% increase in ¹³C₅-glutamate production from the isotope-labeled ¹³C₅-5-oxoproline. This integrated approach, combining enzyme activation with advanced delivery systems, may present a promising therapeutic strategy for oxidative stress-related conditions, particularly conditions like heart failure; it also demonstrates the potential of materials-based solutions for challenging therapeutic targets.

Suction-based in vivo cutaneous DNA transfection is a newly developed, cost-effective method that produces high transfection efficiency. This method has shown robust immunogenic responses following SARS-CoV-2 DNA vaccination in both pre-clinical studies and clinical trials. The current work investigates suction-based transfection and immune activation on a detailed, cellular level. The spatiotemporal patterns of antigen expression in rat skin following suction-induced delivery of a pEGFP-N1 plasmid and a SARS-CoV-2 DNA vaccine are evaluated via immunofluorescence staining, which demonstrates early and prolonged expression. The epidermis is identified as the primary location of transfection, and the transfected cells are primarily epidermal keratinocytes. Early immune response is assessed by detection of major histocompatibility complex class II-positive (MHC-II⁺) cells following suction-induced DNA vaccination.

J. Wang, T. Wen, H. Chen, S. Huang, R. Guo, Y. Zheng, Z. Xiao, X. Shuai, Microneedles-Mediated Intradermal Delivery of Paclitaxel/Anti-PD-1 for Efficient and Safe Triple-Negative Breast Cancer Therapy. Adv. Therap. 2024, 7, 2300362.

https://doi.org/10.1002/adtp.202300362

The authors found that the pictures of control group in Figure 6E were incorrect. The corrected and revised Figure 6E and corresponding figure legend are provided. None of the conclusions of the main text are changed.

We apologize for this error.

Celebrating the ocean's therapeutic wisdom, the cover image highlights the marine ecosystem, portraying it as a living reservoir of bioactive materials that nurture healing and regeneration. Amid the vibrant depth of the sea, interpenetrating polymeric network microparticulate system (IPN MPs), crafted from marine polysaccharides Fucoidan and Laminarin, emerges as radiant microparticles reflecting the synergy of nature and biomaterial engineering. This biocompatible microparticulate system offers potential wound healing activity with pro-migratory effect. The research highlights IPN MPs as a promising biomaterial for advancing next-generation wound care. More details can be found in the Research Article by Subham Banerjee and co-workers (DOI: 10.1002/adtp.202500271).

The cover image of the Research Article (DOI: 10.1002/adtp.202500244) by Katja Hanack, Ramasamy Paulmurugan, and co-workers shows the outcome of a multi-institutional collaborative effort developing a novel camelid antibody (B10) targeting SARS-CoV2 with wide spectrum neutralizing effect. This study systematically characterized the functional neutralizing effect of this antibody using epitope mapping, peptide fragment inhibition, neutralization, in silico molecular docking, and AI-directed structural design, to reveal the interaction of B10 with the Spike trimer from different variants. This newly generated antibody could be a potential candidate to efficiently neutralize a wide range of current and future variants of SARS-CoV-2 for broad clinical applications.

The limitations of conventional cancer treatment can be countered by alternative therapies, such as photodynamic therapy. This technique uses photosensitizing agents (PSs), including zinc phthalocyanines (ZnPc). Nanotechnology has emerged as a strategy to optimize the physicochemical properties of these PSs, promoting controlled release, increased solubility, specificity, and therapeutic action. Thus, this review aims to present the results of in vivo trials conducted over the past decade on nanosystems that use this photosensitizer in cancer treatment. The searches were conducted on Google Scholar, PubMed, and CAPES Journals, using the descriptors “Zinc phthalocyanine”, “Photodynamic therapy”, and “Cancer”, resulting in 10 138 articles. After applying the inclusion and exclusion factors, 40 articles were included. The results revealed that, among the types of cancer addressed in the selected articles, breast cancer was the most frequent in 34% of the studies, followed by others (32%), cervical (14%), colon and cervical, both with 10%. Regarding the nanosystems, polymeric and inorganic nanoparticles were the most used for incorporating ZnPc, each representing 15% of the studies, followed by micelles (10%) and liposomes (10%). The results highlighted the therapeutic potential of these nanosystems, reinforcing their relevance as an innovative, more effective, and safer strategy for cancer treatment.

Current cancer therapies for solid cancers involve surgery, radiotherapy, and chemotherapy, but challenges such as tumor heterogeneity, drug resistance, and poor drug delivery hinder effective treatment. Nano-oncology, specifically liposomes, shows promise by improving drug delivery through better pharmacokinetics and targeting, minimizing toxicity to healthy tissue. Engineered liposomes can enhance drug delivery, and the development of stimuli-responsive nanoparticles offers more precise control over drug release. This study develops a novel all-in-one drug delivery system, using liposomes functionalized with a modified apolipoprotein E peptide (mApoE) for selectively targeting low-density lipoprotein receptor (LDLR) overexpressed on tumor cells and a matrix metalloproteinase 2 (MMP2)-cleavable lipopeptide. The bi-functional liposomes are loaded with Pimasertib, a MAP/ERK kinase inhibitor (MEK1/2), and show enhanced delivery and effectiveness in reducing melanoma cell viability. Furthermore, these liposomes significantly decrease the growth and invasiveness of melanoma 3D spheroids and reduce the expression of epithelial-to-mesenchymal transition markers. These findings highlight the potential of MMP-sensitive, mApoE-functionalized liposomes as effective drug delivery systems for melanoma treatment, providing a promising approach for sustained drug release and targeted therapy in the tumor microenvironment. Moreover, this approach is promising not only for the treatment of melanoma but also for other types of tumors expressing LDLR and MMPs.