查找使用阿拉丁产品的科研文献

Mitochondrial-targeted photodynamic therapy combined with TGF-β inhibition potentiates anti-PD-1 therapy in pancreatic ductal adenocarcinoma

Shijin Xu,Naidi Yang,Fangning Du,Ziying Zhang,Yin Zhang,Yixuan Zhang,Jiawei Liang,Yihan Zhao,Jiajun Zhang,Ziwei Zhang,Xiaoxuan Han,Zena Chen,Zhiqiang Zhou,Shu Zhang,Lin Li,Ying Lv

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, marked by extensive stromal fibrosis and a profoundly immunosuppressive, immune-excluded tumor microenvironment (TME) that hampers the efficacy of immune checkpoint blockade. Although photodynamic therapy (PDT) can induce immunogenic cell death (ICD) and stimulate anti-tumor immunity, its effectiveness against PDAC is limited by insufficient immune activation and persistent stromal-mediated immunosuppression. To address these challenges, we develop a liposomal nanodrug that co-encapsulates a mitochondrial-targeted photosensitizer (MP) and a TGF-β receptor inhibitor (LY2109761) to synergize PDT with PD-1 checkpoint blockade. MP selectively accumulates in mitochondria and, upon light activation, amplifies mitochondrial reactive oxygen species production, inducing mitochondrial damage. This damage triggers the release of mitochondrial DNA and damage-associated molecular patterns, activating the STING pathway and eliciting potent ICD and anti-tumor immune responses. Simultaneously, liposome-mediated delivery of LY2109761 mitigates stromal desmoplasia and reverses TGF-β-driven immune suppression, enhancing effector T cell infiltration and activity. In murine PDAC models, this dual-action strategy transforms the immune-cold TME into an immune-inflamed phenotype, sensitizing tumors to PD-1 therapy and leading to pronounced tumor regression and prolonged survival. Our findings present a promising nanodrug-based approach to remodel the fibrotic and immunosuppressive TME of PDAC and enhance immunotherapeutic outcomes.

Nanoformulated resveratrol enhanced the treatment of atherosclerosis

Cai Cheng,Yan Lin,Xin Chen,Yang Xie,Xing Jiang,Jinting Chen,Yanling Wu,Zaiyi Luo,Jiayi Xu,Zhirong Zhang,Changguang Wang,Pei Jing,Zhongbing Liu,Xingjie Du,Jun Jiang,Xiaoduan Sun,Xiangyu Zhou,Zhirong Zhong

Atherosclerosis, a leading pathological basis of cardiovascular diseases, is closely associated with oxidative stress, inflammation, and lipid metabolism disorders. Resveratrol has demonstrated anti-atherosclerotic activity, but its clinical application is limited due to poor solubility, short circulation time, and lacking targeting. To overcome these limitations and establish a multi-pathway synergistic strategy for treating atherosclerosis, we designed a stealth lipid nanosphere system with macrophage-targeted and pH-responsive properties. The complete lipid nanospheres were evaluated for biocompatibility, cellular uptake, antioxidant and anti-inflammatory activities, as well as the inhibitory effects on foam cell formation. Pharmacokinetics and targeting efficiency were analyzed using both high-performance liquid chromatography and an in vivo imaging system. Therapeutic efficacy and biosafety were assessed via serum biochemistry and histopathological examination. Results showed that the complete lipid nanospheres exhibited uniform spherical morphology, high encapsulation efficiency, and pH-responsive release. In vitro evaluations demonstrated excellent biocompatibility of the complete lipid nanospheres, along with selective uptake by activated macrophages. Furthermore, the complete lipid nanospheres exhibited potent antioxidant and anti-inflammatory effects, as well as significant inhibition of foam cell formation. In vivo studies demonstrated that the treatment significantly extended the plasma half-life of resveratrol while enhancing its targeted accumulation within atherosclerotic plaques. In ApoE −/− mice with atherosclerosis, this intervention exhibited multifaceted therapeutic effects, including attenuation of oxidative stress, suppression of inflammatory responses, and reduction of lipid deposition. The study concludes that the complete formulation, stealth folic acid-modified pH-responsive lipid nanospheres, can specifically target resveratrol to the activated macrophages in plaques and inhibit plaque progression with minimal side effects, primarily due to resveratrol's antioxidant, anti-inflammatory, and lipid metabolism regulatory activities.

Locally delivered hydrogels with controlled release of nanoscale exosomes promote cardiac repair after myocardial infarction

Xi Tan,Jing Zhang,Yongyuan Heng,Lin Chen,Yi Wang,Shaojun Wu,Xiaoli Liu,Biao Xu,Ziyi Yu,Rong Gu

Compared with stem cells, exosomes as a kind of nanoscale carriers intrinsically loaded with diverse bioactive molecules, which had the advantages of high safety, small size, and ethical considerations in the treatment of myocardial infarction, but there are still problems such as impaired stability and rapid dissipation. Here, we introduce a bioengineered injectable hyaluronic acid hydrogel designed to optimize local delivery efficiency of trophoblast stem cells derived-exosomes. Its hyaluronan components adeptly emulates the composition and modulus of pericardial fluid, meanwhile preserving the bioactivity of nanoscale exosomes. Additionally, a meticulously designed hyperbranched polymeric cross-linker facilitates a gentle cross-linking process among hyaluronic acid molecules, with disulfide bonds in its molecular framework enhancing biodegradability and conferring a unique controlled release capability. This innovative hydrogel offers the added advantage of minimal invasiveness during administration into the pericardial space, greatly extending the retention of exosomes within the myocardial region. In vivo, this hydrogel has consistently demonstrated its efficacy in promoting cardiac recovery, inducing anti-fibrotic, anti-inflammatory, angiogenic, and anti-remodeling effects, ultimately leading to a substantial improvement in cardiac function. Furthermore, the implementation of single-cell RNA sequencing has elucidated that the pivotal mechanism underlying enhanced cardiac function primarily results from the promoted clearance of apoptotic cells by myocardial fibroblasts.

Development of tLyP-1 functionalized nanoliposomes with tunable internal water phase for glioma targeting

Yajing Wang,Ziwei Ding,Shiqun Lv,Jie Liu,Jie Pan,Yingcong Yu,Jun Gao,Xianfeng Huang