Macrophages with tumor-tropic migratory properties can serve as a cellular carrier to enhance the efficacy of anti neoplastic agents. However, limited drug loading (DL) and insufficient drug release at the tumor site remain the main obstacles in developing macrophage-based delivery systems. In this study, we constructed a biomimetic delivery system (BDS) by loading doxorubicin (DOX)-loaded reduced graphene oxide (rGO) into a mouse macrophage-like cell line (RAW264.7), hoping that the newly constructed BDS could perfectly combine the tumor-tropic ability of macrophages and the photothermal property of rGO. At the same DOX concentration, the macrophages could absorb more DOX/PEG-BPEI-rGO than free DOX. The tumor-tropic capacity of RAW264.7 cells towards RM-1 mouse prostate cancer cells did not undergo significant change after drug loading in vitro and in vivo. PEG-BPEI-rGO encapsulated in the macrophages could effectively convert the absorbed near-infrared light into heat energy, causing rapid release of DOX. The BDS showed excellent anti-tumor efficacy in vivo. The BDS that we developed in this study had the following characteristic features: active targeting of tumor cells, stimuli-release triggered by near-infrared laser (NIR), and effective combination of chemotherapy and photothermotherapy. Using the photothermal effect produced by PEG-BPEI-rGO and DOX released from the macrophages upon NIR irradiation, MAs-DOX/PEG-BPEI-rGO exhibited a significant inhibitory effect on tumor growth.
Skin diseases are among the most prevalent non-fatal conditions worldwide. The transdermal drug delivery system (TDDS) has emerged as a promising approach for treating skin diseases, owing to its numerous advantages such as high bioavailability, low systemic toxicity, and improved patient compliance. However, the effectiveness of the TDDS is hindered by several factors, including the barrier properties of the stratum corneum, the nature of the drug and carrier, and delivery conditions. In this paper, we provide an overview of the development of the TDDS from first-generation to fourth-generation systems, highlighting the characteristics of each carrier in terms of mechanism composition, penetration method, mechanism of action, and recent preclinical studies. We further investigated the significant challenges encountered in the development of the TDDS and the crucial significance of clinical trials.
Purpose: The clinical management of patients with castration-resistant prostate cancer (CRPC) is difficult. However, novel treatment methods are gradually being introduced. Considering the adverse effects of traditional treatments, recent studies have investigated gene therapy as a method to combat CRPC; but, the application of long non-coding (lnc) RNA in gene therapy remains scarce, despite their promise. Therefore, it is imperative to develop a system that can efficiently deliver lncRNA for the treatment of CRPC. Here, we investigated the efficacy of a delivery system by introducing the plasmid-encoding tumor suppressor lncRNA MEG3 (pMEG3) in CRPC cells. Materials and Methods: An EpDT3 aptamer-linked poly(amidoamine) (PAMAM) dendrimer targeting EpCAM was used to deliver pMEG3 in CRPC cells. The PAMAM-PEG-EpDT3/pMEG3 nanoparticles (NPs) were tested using in vitro cellular assays including cellular uptake, entry, and CCK-8 measurement, and tumor growth inhibition, histological assessment, and safety evaluations in in vivo animal models. Results: The EpDT3 aptamer promoted endocytosis of PAMAM and PAMAM-PEG-EpDT3/pMEG3 NPs in CRPC cells. PAMAM-PEG-EpDT3/pMEG3 NPs exhibited a significant anti-CRPC effect, both in vivo and in vitro, when compared to that of unfunctionalized PAMAM-PEG/pMEG3 NPs. Conclusion: PAMAM-PEG-EpDT3/pMEG3 NPs can potentially improve gene therapy in CRPC cells.
Psoriasis is a chronic autoimmune inflammatory disease characterized by erroneous metabolism of keratinocytes. The development of psoriasis is closely related to abnormal activation and disorders of the immune system. Dysregulated skin protective mechanisms can activate inflammatory pathways within the epithelial immune microenvironment (EIME), leading to the development of autoimmune-related and inflammatory skin diseases. In this review, we initially emphasized the pathogenesis of psoriasis, paying particular attention to the interactions between the abnormal activation of immune cells and the production of cytokines in psoriasis. Subsequently, we delved into the significance of the interactions between EIME and immune cells in the emergence of psoriasis. A thorough understanding of these immune processes is crucial to the development of targeted therapies for psoriasis. Finally, we discussed the potential novel targeted therapies aimed at modulating the EIME in psoriasis. This comprehensive examination sheds light on the intricate underlying immune mechanisms and provides insights into potential therapeutic avenues of immune-mediated inflammatory diseases.
Alopecia areata (AA) is a complex, chronic inflammatory skin disorder characterized by unpredictable, nonscarring hair loss, affecting millions worldwide. Its pathogenesis remains poorly understood, driven by intricate interactions among immune dysregulation, genetic predisposition, and environmental triggers. Despite significant advances in identifying these contributing factors, substantial gaps persist in our understanding of the full spectrum of AA's molecular mechanisms and in the development of effective therapeutic approaches. This review aims to comprehensively explore the immunological, genetic, epigenetic, and environmental factors underlying AA, with a focus on immune‐mediated mechanisms. We also evaluate diagnostic approaches and recent advancements in assessing disease severity. Furthermore, the review discusses evolving therapeutic options, including traditional therapies, biologics, small‐molecule agents, and emerging treatments. The academic value of this work lies in its synthesis of current knowledge on the multifaceted nature of AA, providing insights for future research and clinical practice. By elucidating the interconnected factors underlying AA, this review seeks to advance both understanding and management of this prevalent, clinically challenging disorder.