RSC Advances
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2025
·Vol. 15
·期 20
·15639-15650
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IF 4.6
Zicheng Wan,Dongyang Li,Yang Zhou,Tun Wang,Benyin Zhu,Changhai Du,Yimin Li,Chang Shu
This study presents a preliminary investigation of porous nickel-titanium (NiTi) materials with controllable porosity fabricated through metal injection molding combined with the powder space-holder method (MIM-PSH). The thermosensitive hydrogel Pluronic F-127 was utilized as a drug carrier to load the anti-proliferative drug rapamycin, resulting in porous NiTi-hydrogel composite materials for controlled drug release. By tuning the NiTi matrix porosity (0%, 20%, and 40%), the system achieved precise modulation of drug loading capacity and release kinetics. Notably, the 40% porous NiTi composite exhibited a threefold increase in the drug-loading capacity and sustained release over 17 days. This hybrid design leveraged the thermoresponsive properties of the hydrogel and the tailored pore architecture to enable spatiotemporal control of rapamycin delivery, effectively inhibiting human aortic smooth muscle cell proliferation and mitigating in vivo vascular tissue hyperplasia. This study provides a foundational framework for the development of multifunctional biomaterial systems for vascular therapy.
研究领域:
生物医学工程
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材料科学
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药理学
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PubMed
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MOLECULAR BIOLOGY
·
2024
·
IF 1.5
Yang S. J.,Ying J. L.,Xie W. J.
Abstract Microglia phagocytosis plays an important role in the pathogenesis of neurodegeneration. Defects or dysfunction of microglia phagocytosis were observed in neurodegenerative diseases, with different targets and associated receptors influencing the microglia response. Moreover, non-canonical LC3-associated (microtubule-associated protein 1 light chain 3) phagocytosis was extensively studied recently as a novel form of phagocytosis on macrophages, but little on microglia. Here, we investigated changes in phagocytic function of microglia activated by lipopolysaccharide (LPS) as well as rapamycin-regulated phagocytosis. Phagocytosis in mouse BV2 cells and primary microglia was analyzed by flow cytometry and immunofluorescence. Phagocytosis-related mechanisms in BV2 cells were analyzed using Western blotting and real-time polymerase chain reaction. Rapamycin was shown to reduce LPS-induced phagocytosis of microglia and at the same time stimulate LС3-dependent phagocytosis by regulating Atg3 , Atg4 and Atg7 expression. In addition, in BV2 cells, the PI3K/AKT/mTOR pathway may be involved in phagocytosis. These results suggest that phagocytosis of microglia is a complex process, and the increase in phagocytosis should not be considered as a maturation of phagocytic function. The data will provide new insights into the mechanisms of phagocytosis and neuroimmunity.
研究领域:
神经科学
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免疫学
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细胞生物学
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药理学
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DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
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2022
·
IF 6.064
Boao Xie,Liwei Zhang,Chunyang Lou,Shunbo Wei,Jing’an Li,Hualong Bai,Alan Dardik
Background: Patches are commonly used to close blood vessels after vascular surgery. Most currently used materials are either prosthetics or animal-derived; although natural materials, such as a leaf, can be used as a patch, healing of these natural materials is not optimal; rhodamine and rapamycin have been used to show that coating patches with drugs allow drug delivery to inhibit neointimal hyperplasia that may improve patch healing. Wood is abundant, and its stiffness can be reduced with processing; however, whether wood can be used as a vascular patch is not established. We hypothesized that wood can be used as a vascular patch and thus may serve as a novel plant-based biocompatible material. Method: Male Sprague-Dawley rats (aged 6-8 weeks) were used as an inferior vena cava (IVC) patch venoplasty model. After softening, wood patches coated with rhodamine and rapamycin were implanted into the rat subcutaneous tissue, the abdominal cavity, or the IVC. Samples were explanted on day 14 for analysis. Result: Wood patches became soft after processing. Patches showed biocompatibility after implantation into the subcutaneous tissue or the abdominal cavity. After implantation into the IVC, the patches retained mechanical strength. There was a significantly thinner neointima in wood patches coated with rapamycin than control patches (146.7 ± 15.32 μm vs. 524.7 ± 26.81 μm; p = 0.0001). There were CD34 and nestin-positive cells throughout the patch, and neointimal endothelial cells were Eph-B4 and COUP-TFII-positive. There was a significantly smaller number of PCNA and α-actin dual-positive cells in the neointima ( p = 0.0003), peri-patch area ( p = 0.0198), and adventitia ( p = 0.0004) in wood patches coated with rapamycin than control patches. Piezo1 was expressed in the neointima and peri-patch area, and there were decreased CD68 and piezo1 dual-positive cells in wood patches coated with rapamycin compared to control patches. Conclusion: Wood can be used as a novel biomaterial that can be implanted as a vascular patch and also serve as a scaffold for drug delivery. Plant-derived materials may be an alternative to prosthetics or animal-based materials in vascular applications.
研究领域:
血管外科
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药理学
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生物材料
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生物医学工程
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DOI
PubMed
高影响因子
Biomaterials Science
·
2025
·
IF 5.7
Hui Shi,Yuqiao Ju,Qing Chang,Lian Cen
With the increasing incidence of retinopathy of prematurity (ROP) and the gradual emergence of side effects associated with existing treatments, the development of novel nano-therapy strategies for ROP has become critically urgent. The aim of the current study was to explore the possibility of developing PLGA nanoparticles loaded with rapamycin (RPM) (RPM-PLGA NPs) for the sustained release of RPM as a nano-therapy for ROP intervention. RPM-PLGA NPs were prepared using a nanoprecipitation method, and their physicochemical properties were characterized. The safety profile and therapeutic efficacy of RPM-PLGA NPs were evaluated in BV2, HUVEC cells and in an oxygen-induced retinopathy (OIR) mouse model. RPM-PLGA NPs of 144.23 ± 3.40 nm, a polydispersity index of 0.05 ± 0.02, an encapsulation efficiency of 81.39%, and a drug loading capacity of 16.28% were successfully prepared. The sustained and gradual release of RPM from these NPs was achieved for over 35 days. It was demonstrated that RPM-PLGA NPs had no significant effect on the viability and migration of BV2 and HUVECs. In the oxygen-induced OIR model, RPM-PLGA NPs significantly reduced the areas of vaso-obliteration and pathological neovascularization in the mouse retina, showing superior therapeutic effects compared to RPM alone. These findings validated the feasibility of RPM-PLGA NPs as an intravitreal injection for the treatment of ROP. It is believed that the current study could provide promising experimental data for nano-therapy as an effective and superior treatment for ROP with few side effects.
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ACS Nano
·
2025
·
IF 16
Ximu Li,Mengyao Ma,Ni An,Xiaoxuan Yao,Guzailinuer Yasen,Mingyuan Zhong,Zheng Jin,Zhonggui He,Yongjun Wang,Hongzhuo Liu
Antidrug antibodies (ADAs) against biologics present a major challenge for sustained biotherapy, including enzyme replacement therapies and adeno-associated virus (AAV) gene therapies. These antibodies arise from undesirable immune responses, leading to altered pharmacokinetics, reduced efficacy, and adverse reactions. In this study, we introduced a rationally designed lipid-rapamycin (Rapa)-based nanovaccine to restore immune tolerance to biologics and overcome drug resistance. The nanovaccine significantly decreased ADA responses when used in a tolerogenic regimen with keyhole limpet hemocyanin (KLH), uricase, pegylated uricase, and AAV8 vector gene therapy. This approach facilitated three rechallenges with pegylated uricase after a 5 week rest from the nanovaccine, thereby enhancing its urate-lowering efficacy. Furthermore, the nanovaccine allowed for the successful intravenous readministration of AAV8 vector expressing secreted embryonic alkaline phosphatase (AAV8-SEAP), achieving sustained viral DNA and transcript levels in target tissues. The nanovaccine prompted antigen-presenting cells (APCs) in the liver to exhibit dynamic changes in CD80, CD86, MHCII, and PD-L1, which promoted the development of immunoregulatory T cells in response to biologic challenges. Notably, the nanovaccine exerted a minimal impact on CD8+ T cells, natural killer (NK) cells, and NK T cells, preserving the body’s normal immune response to pathogens and tumors. Overall, the universal nanovaccine addressed biologic resistance by mitigating ADA-related issues, thereby enabling a prolonged therapeutic efficacy for antibodies, proteins, and gene therapies.
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CARBOHYDRATE POLYMERS
·
2019
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IF 6.044
Yuanhao Qiu,Chunbo Lu,Peng Chen,Feifei Sun,Dongdong Wang,Zhaojie Wang,Chunyan Hou,Haibo Mu,Jinyou Duan
Many pathogenic bacteria can invade phagocytic and non-phagocytic cells and colonize inside, which protects them from the attack by host immune system and antibiotics. A novel amphiphilic molecule was synthesized through conjugation of streptomycin and decylamine to hyaluronan. Rapamycin was encapsulted by the spontaneous self-assembly of hyaluronan-based amphiphilic molecules. The newly formed micelles not only facilitated the entry of drugs into host cells in part via CD44 phagocytic receptor, released streptomycin in the acidic compartment, but also could activate autophagy. The micelles elicited an efficient killing capacity against intracellular bacteria through the promotion of streptomycin uptake and rapamycin-initiated activation of autophagy. This strategy might highlight an acid-sensitive hyaluronan-based drug delivery system for effective treatment of intracellular infections.
研究领域:
药理学
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微生物学
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药物递送系统
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传染病
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
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2026
·
IF 4.9
Li Li,Weijia Huang,Zhenyang Zhao,Yuan Gao,Rui Zhang,Zhonghao Liao,Yuxin Hu,Qing Ma,Yang Yang,Yongjun Wang,Hongzhuo Liu
Antidrug antibodies (ADAs) compromise the pharmacokinetics and efficacy of biologics and can trigger adverse reactions. We engineer a tolerogenic liposomal platform in which rapamycin is covalently conjugated to cholesterol (RAPA-chol) and formulated as nanoliposomes (RA-c@L) to induce antigen-specific immune tolerance to coadministered proteins. Covalent anchoring enables high drug encapsulation (>95%) and improves colloidal stability. In a three-dose weekly tolerization regimen with uricase, followed by a high-dose challenge, RA-c@L markedly suppresses ADA formation: by day 42, antiuricase IgG titers are reduced by 2.15-fold compared to uricase alone and 2.17-fold compared to free rapamycin. Responses to an irrelevant antigen (KLH) remain unchanged, indicating antigen specificity. Importantly, coadministration of RA-c@L with rAAV8-SEAP enables vector readministration, yielding approximately 2-fold higher sustained serum SEAP expression after the second dose compared to rAAV alone. Mechanistically, intravenously delivered RA-c@L preferentially accumulates in the liver and reshapes systemic immunity, with reduced splenic T follicular helper cells and germinal-center B cells and an expansion of CD4+Foxp3+ regulatory T cells. Together, these data show that RA-c@L establishes durable, antigen-specific tolerance to therapeutic proteins and facilitates AAV redosing, offering a practical strategy to mitigate ADA-mediated loss of efficacy in repeated biotherapeutic treatments.
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Redox Biology
·
2025
·
IF 11.9
Yutian Zhang,Jingru Wang,Hui Yang,Leting He,Miao Cui,Qinjie Ling,Jingjun He,Shan Gou,Fei Liu,Zhihui Cai,Zhi Huang
Rapamycin (RPM) extends longevity in various species and combats vascular senescence related diseases. Selenium nanoparticles (SeNPs) have attracted attention as a potential therapy for cardiovascular diseases due to their excellent antioxidant and drug-carrying capacity. However, RPM coated SeNPs (RPM-SeNPs) have not been reported and their potential for preventing endothelial oxidative senescence remains unclear. In the present study, RPM-SeNPs were generated by selenite and RPM with ascorbic acid reduction. Stability and dispersity of SeNPs were increased by coating with RPM, resulting in an average diameter of 67.51 ± 2.07 nm with a RPM:Se molar ratio of 1:120. Notably, RPM-SeNPs exhibited ameliorative effects on oxidative endothelial senescence in mouse aortas or MAECs induced by paraquat or hydrogen peroxide, respectively. There were evidenced by decreased SA-β-gal activity, lower SASP levels, and decreased endothelial dysfunction. Mechanically, RPM-SeNPs reduced oxidative stress in endothelial cells by upregulating GPX4, particularly mitochondrial GPX4 (mtGPX4) that mitigated of ROS and relieved mitochondria dysfunction. By downregulating the PI3K/Akt/mTOR pathway, RPM-SeNPs inhibited ULK1 phosphorylation at Ser757, subsequently leading to the activation of mitophagy and the reversal of mitochondrial dysfunction, including mitochondrial membrane potential collapse and ATP deficiency. Thus, these results suggest that RPM-SeNPs rescue endothelial cells from oxidative stress induced senescence by upregulating mtGPX4 and activating mitophagy. These results provide insight into the mechanisms of functionalizing SeNPs for potentially treating senescence-related diseases.
研究领域:
纳米医学
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老年学
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心血管科学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2025
·
IF 4.7
Fengjie Zhang,Shiyu Hu,Yuyuan Ying,Meiru Zhou,Xunuo Wen,Qingru Sun,Zhaohuan Lou,Jianli Gao
Thymus is the core organ that reflects the degree of aging, and the anti-aging effect of rapamycin(RAPA) has been confirmed by multiple studies, but the dynamic changes of the thymus after the administration of RAPA have been lacking systematic research. Here, we observed the involution of thymus induced by RAPA (1 mg/kg/day, i.p. for 3 days) and its regeneration kinetics after withdrawal of RAPA, to explore the possible mechanism of RAPA’s anti-aging effects based on changes in thymus function. The results show that the thymus weight decreased by 46.15% post-RAPA, then regenerated from 20.45 mg to 57.97 mg, reaching 1.3-fold baseline levels in age-matched controls. RAPA can cause acute involution in thymic structure and function, such as loss of medullary thymic epithelial cells (mTECs) and subcapsular thymic epithelial cells (sTECs), abnormal differentiation of thymocytes, reduction of peripheral T cell proportion, and up-regulation of Foxn1 and Klf6 mRNA levels. Regeneration featured expanded double positive (DP) T cells, CD3 + TCRβ + T cells, CD8 single-positive (SP) T cells, medullary dilatation, and thymocyte telomere elongation. IL-7 and MET have pro-regeneration effects, but neither of them could accelerate RAPA-mediated thymic regeneration. IL-7 can prolong telomere length of thymocytes and restore peripheral T cell homeostasis, while MET can promote T cell positive selection and increase Sirt3 and Gimap4 mRNA levels. These results demonstrate that RAPA triggers transient thymic suppression followed by thymus volume and functional recovery. It seems that RAPA-mediated immune reconstitution may be an important reason for the potential anti-aging effect of RAPA.
研究领域:
免疫学
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衰老研究
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药理学
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细胞生物学
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分子生物学
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PubMed
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Bohong Yu,Yubo Liu,Yingxi Zhang,Linyi Xu,Kai Jin,Andi Sun,Xiuli Zhao,Yongjun Wang,Hongzhuo Liu
Mitochondrial dysfunction plays a major role in driving acute kidney injury (AKI) via alteration in energy and oxygen supply, which creates further ROS and inflammatory responses. However, mitochondrial targeting medicine in recovering AKI is challenging. Herein, we conjugated SS31, a mitochondria-targeted antioxidant tetrapeptide connecting a cleavable linker to rapamycin (Rapa), which provided specific interaction with FK506-binding protein (FKBP) in the RBCs . Once entering the bloodstream, SS31-Rapa could be directed to the intracellular space of RBCs, allowing the slow diffusion of the conjugate to tissues via the concentration gradient . The new RBC hitchhiking strategy enables the encapsulation of conjugate into RBC via a less traumatic and more natural and permissive manner, resulting in prolonging the t 1/2 of SS31 by 6.9 folds. SS31-Rapa underwent the direct cellular uptake, instead of the lysosomal pathway, released SS31 in response to activated caspase-3 stimulation in apoptotic cells, favoring the mitochondrial accumulation of SS31. Combined with autophagy induction associated with Rapa, a single dose of SS31-Rapa can effectively reverse cisplatin and ischemia reperfusion-induced AKI. This work thus highlights a simple and effective RBC hitchhiking strategy and a clinically translatable platform technology to improve the outcome of other mitochondrial dysfunctional related diseases.
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高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 22
·4882-4889
·
IF 7
Yu-xian Lai,Jia-yin Fu,Shao-fei Wu,Ren-yun Li,Jia-qi Hu,You-xiang Wang,M. Cristina L. Martins,Ke-feng Ren,Jian Ji,Guo-sheng Fu
Drug-coated balloon (DCB) is a therapeutic method that can effectively deliver antiproliferative drugs such as paclitaxel and rapamycin (RAPA) with no permanent implants left behind. However, delayed reendothelialization due to the toxicity of the delivered drugs leads to poor therapeutic effects. Here, we propose a new design of DCB coating, which incorporates both vascular endothelial growth factor (VEGF)-encoding plasmid DNA (pDNA) that can promote endothelial repair and RAPA into protamine sulfate (PrS). We demonstrate that the PrS/pDNA/RAPA coating had stability and good anticoagulation properties in vitro. We further show that the coating exhibited excellent transfer capacity from balloon substrates to vessel walls both in vitro and in vivo. Furthermore, the PrS/pDNA/RAPA coating effectively inhibited neointimal hyperplasia after balloon-induced vascular injuries through the down-regulation of the mammalian target of Rapamycin (mTOR) and promoted endothelium regeneration through increased expression of VEGF in vivo. These data indicate that our nanocomposite coating has great potential for use as a novel coating of DCB to treat neointimal hyperplasia after vascular injuries.
研究领域:
心血管医学
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药学
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生物医学工程
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PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2023
·
IF 2.9
Weiqian Wu,Ruilai Liu,Jiahao Guo,Zhihuan Hu,Chenjing An,Yan Zhang,Tengyuan Liu,Lian Cen,Yukun Pan
The high hydrophobicity and low oral availability of immunosuppressive drug, rapamycin, seriously limit its application. It was thus aimed to develop a PEG-PLGA based nano-loading system for rapamycin delivery to achieve improved bioavailability with sustained effects via a novel microfluidic chip and manipulation of the hydrophobic PLGA chain length. PDMS based microfluidic chip with Y shape was designed and PEG-PLGA polymers with different PLGA chain length were used to prepare rapamycin nano-delivery systems. Dendritic cells were selected to evaluate the immunosuppressive effect of the nanoparticles including cytotoxicity assay, dendritic cell activation, and cytokine levels. The effects of different PEG-PLGA nanoparticles on the immunomodulatory properties were finally compared. It was shown that PEG-PLGA could be successfully used for rapamycin encapsulation via microfluidics to obtain nano-delivery systems (Rapa&P-20 k, Rapa&P-50 k and Rapa&P-95 k) ranging from 100 nm to 116 nm. The encapsulation efficiency was ranged from 69.70% to 84.55% and drug loading from 10.45% to 12.68%. The Rapa&P-50 k (PLGA chain length: 50 k) could achieve the highest drug loading (DL) and encapsulation efficiency (EE) as 12.68% and 84.55%. The encapsulated rapamycin could be gradually released from three nanoparticles for more than 1 month without any noticeable burst release. The Rapa & P nanoparticles exhibited enhanced immunosuppressive effects over those of free rapamycin as shown by the expression of CD40 and CD80, and the secretion of IL-1β, IL-12 and TGF-β1. Rapa&P-50 k nanoparticles could be the optimal choice for rapamycin delivery as it also achieved the most effective immunosuppressive property. Hence, this study could provide an efficient technology with superior manipulation to offer a solution for rapamycin delivery and clinical application.
研究领域:
药学
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纳米技术
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免疫学
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药物递送系统
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DOI
PubMed
高影响因子
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