JOURNAL OF CONTROLLED RELEASE
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2016
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IF 7.441
Jinping Wang,Fang Guo,Meng Yu,Li Liu,Fengping Tan,Ran Yan,Nan Li
Imaging-guided photothermal therapy (PTT) has promising application for treating tumors. Nevertheless, so far imaging-guided photothermal drug-delivery systems have been developed with limited success for tumor chemo-photothermal therapy. In this study, as the proof-of-concept, a stimuli-responsive tumor-targeting rapamycin/DiR loaded lipid-polyaniline nanoparticle (RDLPNP) for dual-modal imaging-guided enhanced PTT efficacy is reported for the first time. In this system, polyaniline (PANI) with π-π electronic conjugated system and effective photothermal efficiency is chosen as the appropriate model receptor of fluorescence resonance energy transfer (FRET), and loaded cyanine probe (e.g., 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide, DiR) acts as the donor of near-infrared fluorescence (NIRF). In addition, rapamycin (RAPA), which is used as the antiangiogenesis chemotherapeutic drug, can cutdown the tumor vessels and delay tumor growth obviously. After intravenous treatment of RDLPNPs into Hela tumor bearing mice, fluorescent (from DiR) and enhanced photoacoustic (from DLPNPs) signals were found in tumor site over time, which reached to peak at the 6 h time point. After irradiating with an NIR laser , a good anti-tumor effect was observed owing to the enhanced photothermal and antiangiogenic effect of RDLPNPs. These results show that the multifunctional nanoparticle can be used as a promising imaging-guided photothermal drug delivery nanoplatform for cancer therapy.
研究领域:
癌症治疗
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纳米技术
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药学
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生物医学工程
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DOI
PubMed
高影响因子
RSC Advances
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2026
·Vol. 16
·期 2
·1078-1094
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IF 4.6
Dandan Wang,Xiaojing Zhang,Lingpeng Tang,Shengnan Wang,Yifang He,Jiamin Liu,Yanli Wang,Shijie Zhang,Jiangqiong Lai,Guorong Lyu
Atherosclerosis (AS), the primary cause of cardio-cerebrovascular diseases, is characterized by plaques that trigger acute ischemic events. Current therapies face challenges in targeted delivery and efficient local drug release, limiting precise diagnosis and treatment. To address this, we developed an ultrasound-responsive nanosystem for integrated AS diagnosis and therapy. The nanosystem, based on polylactic-co-glycolic acid (PLGA), encapsulates perfluoropentane (PFP) and rapamycin (RAP), and is surface-modified with PP1 peptide (PPP@RAP NPs). The NPs exhibited an average size of 162.63 nm and a drug loading capacity of 36.95%, demonstrating excellent targeting ability. Low-intensity pulsed ultrasound (LIPUS) induced the phase transition of PFP, enhancing ultrasound signals by 85.64% and enabling controlled drug release. In vivo studies showed a significant reduction in lesion lipid area by 25.99% (P < 0.001), highlighting the therapeutic efficacy of the nanosystem. This ultrasound-triggered, peptide-targeted strategy integrates imaging and therapy, offering a promising approach for precise AS intervention with significant clinical translational potential.
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产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2022
·
IF 6.819
Peng Sun,Haoliang Wu,Hao He,Liwei Zhang,Yuanfeng Liu,Cong Zhang,Chunyang Lou,Jingan Li,Hualong Bai
Neointimal hyperplasia is a complex process after vascular interventions, acute platelet deposition and smooth muscle cell proliferation both contributed to this process. There are still no perfect solutions to solve this problem. Rivaroxaban is a novel anticoagulant that has been widely used in clinic, it has a good pharmacological effects both in vivo and in vitro. Chitosan microparticle rapamycin (MP-rapa) was fabricated, interspaces of polyglycolic acid (PGA) scaffold were used as a reservoir of MP-rapa, and the scaffold was coated with hyaluronic acid rivaroxaban (MP-rapa-riva). Scanning electronic microscopy (SEM) photographs were taken and water contact angles were measured, rat inferior vena cava (IVC) patch venoplasty model was used; patches were harvested at day 14 and examined by immunohistochemistry and immunofluorescence. SEM photographs showed the microparticles rapamycin were inside the interspace of the scaffold, hyaluronic acid rivaroxaban was also successfully coated onto the surface of the scaffold. There was a thinner neointima, fewer proliferating cell nuclear antigen (PCNA) positive cells, fewer macrophages in the MP-rapa and MP-rapa-riva grafts compared to the control PGA graft. The result showed that this scaffold with dual anticoagulation and antiproliferation functions can effectively inhibit venous neointimal hyperplasia, although this is an animal experiment, it showed promising potential clinical application in the future.
研究领域:
药理学
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生物医学工程
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血管外科
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材料科学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Rui Wang,Jian Lu,Jiasheng Yin,Han Chen,Hongmei Liu,Fei Xu,Tongtong Zang,Rende Xu,Chenguang Li,Yizhe Wu,Qilin Wu,Xiang Fei,Meifang Zhu,Li Shen,Junbo Ge
An increased level of reactive oxygen species (ROS) plays a major role in endothelial dysfunction and vascular smooth muscle cell (VSMC) proliferation during in-stent thrombosis and restenosis after coronary artery stenting. Herein, we report an electrospun core-shell nanofiber coloaded with 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL) and rapamycin (RAPA) that correspondingly serves as an ROS scavenger and VSMC inhibitor. This system has the potential to improve the biocompatibility of current drug-eluting stent (DES) coatings with the long-term and continuous release of TEMPOL and rapamycin. Moreover, the RAPA/TEMPOL-loaded membrane selectively inhibited the proliferation of VSMCs while sparing endothelial cells (ECs). This membrane demonstrated superior ROS-scavenging, anti-inflammatory and antithrombogenic effects in ECs. In addition, the membrane could maintain the contractile phenotype and mitigate platelet-derived growth factor BB (PDGF-BB)-induced proliferation of VSMCs. In vivo results further revealed that the RAPA/TEMPOL-loaded covered stents promoted rapid restoration of vascular endothelium compared with DES and persistently impeded inflammation and neointimal hyperplasia in porcine models.
研究领域:
生物医学工程
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药学
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心脏病学
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材料科学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2023
·
IF 8.2
Qing Zhang,Mengyu Xin,Shuang Yang,Qiuyu Wu,Xi Xiang,Tianqi Wang,Wen Zhong,Marco N. Helder,Richard T. Jaspers,Janak Lal Pathak,Yin Xiao
Targeting macrophages to regulate the immune microenvironment is a new strategy for bone regeneration with nano-drugs. Nano-drugs have achieved surprising anti-inflammatory and bone-regenerative effects, however, their underlying mechanisms in macrophages remain to be clarified. Macrophage polarization, immunomodulation, and osteogenesis are governed by autophagy. Rapamycin, an autophagy inducer, has shown promising results in bone regeneration, but high dose-mediated cytotoxicity and low bioavailability hinder its clinical application. This study aimed to develop rapamycin-loaded virus-like hollow silica nanoparticles ( [email protected] ) which are easily phagocytosed by macrophages and translocated to lysosomes. [email protected] induced macrophage autophagy, promoted M2 polarization, and alleviated the degree of M1 polarization as indicated by the downregulation of inflammatory factors IL-6, IL-1β, TNF-α, and iNOS, and upregulation of anti-inflammatory factors CD163, CD206, IL-1ra, IL-10, and TGF-β. These effects were nullified by cytochalasin B-induced inhibition of [email protected] uptake in macrophages. The conditioned medium (CM) collected from [email protected] macrophages promoted osteogenic differentiation of mouse bone marrow mesenchymal stromal cells (mBMSCs). In a mouse calvaria defect model, free rapamycin treatment was inhibited, but [email protected] robustly promoted bone defect healing. In conclusion, silica nanocarrier-mediated intracellular rapamycin delivery to macrophages effectively triggers autophagy-mediated M2 macrophage polarization, further enhancing bone regeneration by triggering osteogenic differentiation of mBMSCs.
研究领域:
纳米医学
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免疫学
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骨再生
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2026
·Vol. 17
·期 1
·123
·
IF 7.8
Du Mengxian,Guo Fengyi,Liu Xinna,Zhang Shiqi,Zhang Di,Qiu Leyi,Zhang Jingyang,Li Baoqiang,Yuan Huiping
Background Normal tension glaucoma (NTG) causes progressive retinal ganglion cell (RGC) loss without elevated intraocular pressure, and currently lacks effective neuroprotective therapies. OPTN(E50K) mutation, a pathogenic gene of NTG, compromises paracrine trophic capacity in bone marrow (BM) stem cells. Allogeneic young BM stem cells can provide trophic support and exhibit therapeutic potential; however, their clinical application is limited by immunogenic rejection and tumorigenic risks, prompting a renewed interest in rejuvenate autologous BM stem cells strategy. Methods To address these challenges, we developed a composite chitosan-rapamycin (RAPA) carbon dots (CRCD) to restore the reparative potential of autologous BM stem cells. BM stem cells from aged OPTN(E50K) mice were isolated, clustered and treated with CRCD before validated their changes of neurotrophic factors expression as well as oxidative stress and autophagy indicators. Then we assessed their impact on co-cultured retinas in vitro. Transplantation were performed into lethally irradiated age-matched OPTN(E50K) hosts with CRCD-pretreated autologous BM stem cells via tail vein injection, and generated stable chimeric models. Neurotrophic factors and neuron apoptosis analyses were performed, followed by the visual behavioral tests. Results Our results demonstrated that CRCD pretreatment enhanced autophagy, reduced oxidative stress, and augmented paracrine neurotrophic release. In vitro, these cells reduced retinal ganglion cell apoptosis and promoted neurotrophic factor expression in co-cultured retinal explants. In vivo, comparative analysis revealed that CRCD intervention significantly elevated neurotrophic factor expression in retinal tissues compared to RAPA-treated and untreated chimeras. Functional assessments further confirmed superior visual performance in CRCD-Sca-1 + chimeras, correlating with improved RGC survival. Conclusion These findings suggest that CRCD improved paracrine neurotrophic support of autologous BM stem cells by enhancing their autophagy and paracrine functions, leading to structural and functional rescue of the glaucomatous retina. This approach offered a clinically relevant strategy for NTG, providing sustained neuroprotection while avoiding the risks of allogeneic transplantation and repeated intravitreal drug delivery. Graphical The alternative text for this image may have been generated using AI.
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DOI
高影响因子
AQUACULTURE RESEARCH
·
2023
·
IF 2
Kai Liao,Qian Zhang,Yangyang Qiu,Yuxiang Zhu,Yang Liu,Hailong Huang,Deshui Chen,Bin Ma,Lin Zhang,Zhaoshou Ran,Xiaojun Yan,Jilin Xu
It is of great significance for bivalve aquaculture to promote the growth through nutritional strategy. Phosphatidic acid (PA) is a potential growth-promoting nutraceutical that targets for mammalian target of rapamycin (mTOR) in vertebrates, but its role in invertebrates remains largely unknown. Here, the effects of PA on mTOR and metabolic pathways in bivalve mollusk Sinonovacula constricta were determined by intramuscular injection with di-18 : 2 PA and di-16 : 0 PA. PA (both di-18 : 2 and di-16 : 0 PA) was found to increase the glycogen concentration in the muscle of S. constricta. Di-16 : 0 PA decreased the triglyceride concentration from 0.143 ± 0.04 mmol/g protein to 0.040 ± 0.018 mmol/g protein. The concentration of Asp, Glu, Ala, Cys, Val, Met, Ile, Leu, Phe, Arg, and Pro was reduced by di-18 : 2 PA or/and di-16 : 0 PA. PA increased the mRNA level of mTOR and the phosphorylation levels of eIF4E binding protein 1 and p70S6 kinase 1. Furthermore, PA decreased the protein level of microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ and the mRNA level of AMP-activated protein kinase. The mRNA expressions of two key enzymes of glycolysis (pyruvate kinase and glucokinase) were also upregulated by both PA, while the mRNA level of glucose transporter 1 was increased by di-18 : 2 PA. Di-16 : 0 PA decreased the mRNA level of phosphoenolpyruvate carboxykinase. The mRNA levels of sterol responsive element binding protein, fatty acid synthase, and acetyl-CoA carboxylase were increased by both PA. The mRNA level of stearoyl-CoA desaturase was increased by di-18 : 2 PA. Both PA species increased the mRNA levels of key enzymes involved in tricarboxylic acid cycle (citrate synthase and NADP-isocltrate debydrogenase). Our results indicated that PA activated mTOR signaling pathway, subsequently leading to the increase of anabolism and the inhibition of catabolism in S. constricta.
研究领域:
水产养殖
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分子生物学
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营养学
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生物化学
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DOI
高影响因子
Biomaterials Advances
·
2022
·
IF 0
Tianshu Chu,Chun Dai,Xiang Li,Lei Gao,Hongyan Yin,Jianjun Ge
Following vein grafting, the vein must adapt to arterial hemodynamics, which can lead to intimal hyperplasia (IH) and restenosis. Moreover, endothelial-to-mesenchymal transition (EndMT) components are highly associated with IH. Therefore, in this study, we aimed to design an extravascular film loaded with rapamycin (extravascular rapamycin film [ERF]) to limit vein graft stenosis. The film exhibited stable physicochemical properties as well as in vivo and in vitro biocompatibility. In vivo , the film inhibited the EndMT by activating the autophagy pathway. Moreover, rapamycin enhanced this biological effect. Collectively, these findings highlighted the applicability of ERF as a new therapeutic target for preventing vein graft restenosis.
研究领域:
心血管医学
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药理学
·
组织工程
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产品关联
DOI
PubMed
MATERIALS & DESIGN
·
2022
·
IF 9.417
Bo Chen,Jibing Wang,Xing Jin,Xin Wang,Zhangling Fan,Yuxin Zhang,Xuehan Sang,Zhaoxiang Meng
In the macrophage-specific mTORC1 signaling activation model, the synovial macrophages polarized toward M1, thus aggravating synovitis and progression of OA. Therefore, intra-articular injection of rapamycin, a classical mTORC1 inhibitor, may show great potential for alleviating synovitis and delaying cartilage destruction in osteoarthritis (OA). However, the durable retention of drugs in the joint cavity is still a critical issue to be addressed. Herein, we crosslinked the Poloxamer 407 and hyaluronic acid (P-HA) to prepare an injectable and thermo-responsive drug delivery system to durably retain rapamycin and dramatically magnify their therapeutic effects in OA management. The prepared P-HA hydrogel showed excellent biocompatibility with chondrocytes and fibroblasts, as well as possessed sustained rapamycin release profiles for 14 days. Intra-articular injection of this rapamycin-incorporated P-HA hydrogel indicated a positively effect on inducing the polarization of synovial macrophages from M1 to M2 phenotype and reducing synovial inflammation in OA. This strategy significantly decreased the pro-inflammatory cytokines ( e.g. , TNF-α, IL-1β, and IL-6) and increased the anti-inflammatory cytokine ( e.g. , IL-10) expression in the synovial tissues and synovial fluid. As a result, intra-articular injection of rapamycin-incorporated P-HA hydrogel significantly prevented cartilage destruction by inducing cartilage matrix formation, which suggesting a great potential for the management of OA.
研究领域:
药理学
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生物医学工程
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骨科
·
免疫学
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产品关联
DOI
高影响因子
CELL TRANSPLANTATION
·
2018
·Vol. 27
·期 8
·1235-1248
·
IF 2.885
Wei Zhang,Wan Xu,Wenli Chen,Quan Zhou
MG132 is a pivotal inhibitor of the ubiquitin-proteasome system (UPS), and rapamycin (RAPA) is an important inducer of autophagy. MG132 and RAPA have been shown to be effective agents that can cure multiple autoimmune diseases by reducing inflammation. Although individual MG132 and RAPA showed protective effects for atherosclerosis (AS), the combined effect of these two drugs and its molecular mechanism are still unclear. In this article we investigate the regulation of oxidative modification of low-density lipoprotein (ox-LDL) stress and foam cell formation in the presence of both proteasome inhibitor MG132 and the autophagy inducer RAPA to uncover the molecular mechanism underlying this process. We established the foam cells model by ox-LDL and an animal model. Then, we tested six experimental groups of MG132, RAPA, and 3MA drugs. As a result, RAPA-induced autophagy reduces accumulation of polyubiquitinated proteins and apoptosis of foam cells. The combination of MG132 with RAPA not only suppressed expression of the inflammatory cytokines and formation of macrophage foam cells, but also significantly affected the NF-κB signaling pathway and the polarization of RAW 264.7 cells. These data suggest that the combination of proteasome inhibitor and autophagy inducer ameliorates the inflammatory response and reduces the formation of macrophage foam cells during development of AS. Our research provides a new way to suppress vascular inflammation and stabilize plaques of late atherosclerosis.
研究领域:
心血管疾病
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药理学
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分子生物学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Xi Jiang,Congyan Liu,Qun Zhang,Yanli Lv,Chen Lu,Wenting Su,Jing Zhou,Huangqin Zhang,Huiling Gong,Yuping Liu,Songtao Yuan,Yan Chen,Ding Qu
Autophagic dysfunction-induced deterioration of the retinal microenvironment drives the progression of wet age-related macular degeneration (wAMD). The efficacy of single-target anti-VEGF antibodies in treating wAMD has long been suboptimal due to the intricate interplay between autophagy dysfunction, oxidative stress, and angiogenesis. Here, we introduce an intravitreal hydrogel depot, named Rab&Rapa-M@G, consisting of rapamycin-loaded microemulsion (Rapa-M, an mTOR inhibitor), ranibizumab (anti-VEGF antibody), and a thermosensitive hydrogel matrix. A single intravitreal injection of Rab&Rapa-M@G can sustainably deliver Rapa-M and ranibizumab to the retinal pigment epithelium for at least 14 days. This formulation significantly improves retinal autophagic flux homeostasis and reduces oxidative stress injury in wAMD mice by modulating the AMPK/mTOR/HIF-1α/VEGF and AMPK/ROS/HO-1/VEGF pathways. Consequently, it synergistically disrupts the “autophagic dysfunction-oxidative stress-angiogenesis” loop, leading to a remarkable reduction in choroidal neovascularization area and retinal damage compared to ranibizumab alone. Notably, the sequential administration of ranibizumab and Rab&Rapa-M@G further enhances the overall anti-wAMD efficacy, achieved through sequential delivery of Rab and Rapa, allowing for a more precise grasp of the treatment window. In conclusion, this hydrogel depot design, with its sequential and sustained delivery of mTOR inhibitors and anti-VEGF antibodies, offers a promising strategy for multi-target synergistic therapy in wAMD.
研究领域:
眼科
·
药剂学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
World Journal of Stem Cells
·
2020
·
IF 3.231
Jun-Hao Lei,Wen Yan,Chun-Hua Luo,Yu-Ming Guo,Yang-Yang Zhang,Xing-Huan Wang,Xin-Jun Su
BACKGROUND With continuous advancement of industrial society, environmental pollution has become more and more serious. There has been an increase in infertility caused by environmental factors. Nonylphenol (NP) is a stable degradation product widely used in daily life and production and has been proven to affect male fertility. However, the underlying mechanisms therein are unclear. Thus, it is necessary to study the effect and mechanism of NP on spermatogonial stem cells (SSCs). AIM To investigate the cytotoxic effect of NP on SSCs via the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway. METHODS SSCs were treated with NP at 0, 10, 20 or 30 µmol. MTT assay was performed to evaluate the effect of NP on the proliferation of SSCs. Flow cytometry was conducted to measure SSC apoptosis. The expression of Bad, Bcl-2, cytochrome-c, pro-Caspase 9, SOX-2, OCT-4, Nanog, Nanos3, Stra8, Scp3, GFRα1, CD90, VASA, Nanos2, KIT, PLZF and PI3K/AKT/mTOR-related proteins was observed by western blot, and the mRNA expression of SOX-2, OCT-4 and Nanog was detected by quantitative reverse transcription polymerase chain reaction. RESULTS Compared with untreated cells (0 μmol NP), SSCs treated with NP at all concentrations showed a decrease in cell proliferation and expression of Bcl-2, Nanog, OCT-4, SOX-2, Nanos3, Stra8, Scp3, GFRα1, CD90, VASA, Nanos2, KIT, and PLZF ( P < 0.05), whereas the expression of Bad, cytochrome-c, and pro-Caspase 9 increased significantly ( P < 0.05). We further examined the PI3K/AKT/mTOR pathway and found that the phosphorylation of PI3K, AKT, mTORC1, and S6K was significantly decreased by NP at all concentrations compared to that in untreated SSCs ( P < 0.05). NP exerted the greatest effect at 30 μmol among all NP concentrations. CONCLUSION NP attenuated the proliferation, differentiation and stemness maintenance of SSCs while promoting apoptosis and oxidative stress. The associated mechanism may be related to the PI3K/AKT/mTOR pathway.
研究领域:
毒理学
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生殖生物学
·
环境健康
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）