JOURNAL OF NANOPARTICLE RESEARCH
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2024
·Vol. 26
·期 6
·1-14
·
IF 2.1
Fan Zhechen,Chen Yishan,Li Qian,Gadora Khalid,Ji Zhongsheng,Wu Dong,Zhou Jianping,Ding Yang,Cheng Hao
As a promising antitumor strategy, combination oncotherapy can achieve better therapeutic efficacy. However, given the different properties of drugs, carriers need to meet requirements for efficient encapsulation and controllable release of multi-drugs. Herein, we propose a graphene oxide (GO)-templated biomineralization nanosystem to optimize oncotherapy. For preparation, GO is conjugated with polyethylene glycol (PEG) to improve biostability, and glyeyrrhetinic acid (GA) is further grafted onto PEG chains for site-specific targeting. The generated nanosheet structure and large specific surface area support high doxorubicin (DOX) encapsulation and mineralized deposition of siRNA via π-π stacking and calcium phosphate co-precipitation, respectively. Followed by highly efficient penetration into tumor cells, GO-templated nanosystem performs swift drug release in response to tumor acidic microenvironment through dissolution of calcium phosphate and disruption of molecular interactions. After administration, the GO-templated nanosystem performs superior pharmacy properties and significant antitumor efficacy via the synergy of chemotherapy and RNA interference therapy. Collectively, a GO-templated biomineralization nanosystem provides an innovative delivery system for multi-drug administration in combinative tumor therapy.
研究领域:
纳米技术
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药学
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癌症研究
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药物递送系统
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生物医学工程
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产品关联
DOI
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Jilong Wang,Chenghu Wu,Yiran Wang,Yecheng Shen,Kerui Wu,Yikai Shi,Tianshou Cao,Shanshan Yuan,Yuting Zhu,Yongheng Bai,Jinhai Huang,Yan Zhang,Junjie Deng
Low-expression antigens, especially neoantigens, pose a significant challenge in immunotherapy for low immunogenicity pancreatic cancer. Increasing the tumor mutation burden is crucial to enhance the expression of tumor antigens and improve tumor immunogenicity. However, the incomplete intervention in DNA stability hampers effective elevation of the tumor mutation burden, thus reducing the probability of neoantigen. To address this issue, we have developed a novel nano-regulator that intervenes in the DNA stability of tumor cells, thereby enhancing tumor mutations. This nano-regulator comprises metal-organic frameworks (MOFs) encapsulating DNA damage agent doxorubicin and DNA damage repair inhibitor siRNA-ATR, enabling simultaneous induction of DNA mutations and inhibition of their repair. Importantly, this regulator, named as MOF DOX&siATR , can modulate the tumor gene expression profile, induce the production of neoantigens of Atp8b1, and enhance the immunogenicity of pancreatic cancer. The characteristics of DNA stability intervention by MOF DOX&siATR hold promise for augmenting the immune response in low immunogenic tumors, making it a potential nanomedicine for the treatment of pancreatic cancer.
研究领域:
癌症生物学
·
纳米技术
·
免疫疗法
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2024
·
IF 27.4
Ruonan Wang,Huixin Li,Shasha He,Yuanji Feng,Cong Liu,Kai Hao,Danhua Zhou,Xiaoyuan Chen,Huayu Tian
Lymph nodes are crucial immune foci as the primary target for cancer immunotherapy. However, the anti-tumor functions of tumor-draining lymph nodes (TDLNs) are critically suppressed by tumors. Here, a novel spatiotemporal nano-regulator is presented, designed to modulate the dendritic cells (DCs) in TDLNs, establishing a supportive niche for immune surveillance. The DC-mediated nano-regulator (DNR) is established by the self-assembly of an imidazoquinoline (IMDQ) prodrug, inhibitory immune checkpoint (ICP) siRNA, and mannan (a TLR4 agonist). This unique design leverages the spatiotemporal activation of TLR4 and TLR7/8, thereby optimizing DC maturation and cytokine production. This further promotes efficient T cell priming. Simultaneously, the ICP-targeting siRNA mitigates the tolerogenic effects induced by tumor-derived factors and TLR activation, preventing T cell exhaustion. In essence, DNR facilitates potent remodeling of TDLNs and the tumor microenvironment, activating the anti-tumor immunity cascade. When combined with vaccines, DNR greatly promotes tumor regression and the establishment of long-term immunological memory.
研究领域:
癌症免疫疗法
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免疫学
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纳米医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2022
·
IF 9.965
Feng Wang,Yi Jin,Xin Gao,Haoran Huo,Bei Wang,Biao Niu,Zihan Xia,Jinchao Zhang,Xinjian Yang
Multifunctional therapeutic nanoplatforms with an activatable property have demonstrated the ability to enhance cancer therapy due to their intrinsic controllability in drug delivery. Although much effort has been focused on constructing multifunctional therapeutic nanoplatforms with an activatable property, developing logically activatable nanoplatforms to exert improved therapeutic efficiency against cancer remains an imperative need. In this study, we established a tumor microenvironment activable nanoplatform by the DNAzyme assisted coating of polyaniline (PANI) on the surface of mesoporous silica nanoparticles (MSNs). This mild synthetic strategy can avoid the destruction of the loaded biomolecules and guarantee the biosafety of the nanoplatforms. Furthermore, the activable polymer can be used to load siRNA for combined cancer treatment. When the composite nanoplatforms were enriched in the tumor, the acidic tumor microenvironment activated the nanocarrier and unloaded the drugs and siRNA upon near-infrared (NIR) irradiation to achieve controlled drug delivery for enhanced cancer therapy.
研究领域:
生物医学工程
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癌症治疗
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纳米技术
·
分子生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2024
·
IF 2.7
Yonghua Zhai,Lili Wu,Jie Gao,Jingsheng Zhou,Longhai Du,Xiaoda Fu,Yang Gao,Tinglin Zhang,Mengya Zhang,Weihong Lu,Yan Wu
Smart gene delivery vectors are gaining increasing attention in gene therapy, owing to their low cytotoxicity and intrinsic responsiveness. Our previously fabricated novel cationic brush polymer, comprising C Se bonds and tertiary amine EGIn- g -PDMAEMA, shows potential for gene transfection. In this study, its high efficiency for siRNA/pDNA transfection and low cytotoxicity in reactive oxygen species (ROS)-rich microenvironments is substantiated in vitro. Its superior binding capacity with siRNA/pDNA is confirmed by agarose gel electrophoresis assay. The threshold weight ratios for siRNA/pDNA migration delay are 15 and 3 (polymer-to-nucleic acid, w/w), respectively. Fluorescence microscopy and ribonucleotide reductase regulatory subunit M2 gene silencing essay verify the biodegradability and responsive control release of nucleic acids under hydrogen peroxide stimulation in Huh-7 cells. Compared with the gold standard, polyethylenimine 25 kDa, the target polymer displays superior transfection efficiency in ROS-rich tumor cells under serum-free conditions. Furthermore, the vector–nucleic acid complexes exhibit over 90% cell viability at a high concentration of 12 μg mL −1 and good colloidal stability in phosphate-buffered saline (PBS) and 10% fetal bovine serum-PBS for 24 h. The efficient control release and expression of nucleic acids in ROS environments and reduced cytotoxicity highlight the superiority of EGIn- g -PDMAEMA as a gene delivery platform for tumor gene therapy.
研究领域:
生物医学工程
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基因治疗
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材料科学
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分子生物学
✓ 已验证
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Siwen Wu,Mengmeng Dai,Jiani Zhang,Yusi Wang,Rui Zhang,Hailong Zhang,Li Yang
Myocardial ischemia reperfusion (I/R) injury frequently impacts the outcome of patients with coronary heart disease and lacks effective therapeutic strategies. We have summarized the challenges in treating IR injury into three aspects, namely inflammatory reaction, fibrosis, and impaired proliferation ability of myocardial tissue. To address these issues, we have developed an injectable composite microgel called DMP@mgel by integrating three types of biomaterials: placental-derived mesenchymal stem cells loaded microgel, PEDOT:PSS loaded microgel, and siRNA-loaded carrier DP7-C. Upon injection into the injured area, DMP@mgel could regulate the inflammatory microenvironment, promote angiogenesis by the function of stem cells paracrine. Additionally, it enhances coupling between myocardial cells due to its high electrical conductivity. Moreover, DP7-C/siRNA complex can efficiently transfect into myocardial cells to inhibit Hippo pathway activity and promote cell proliferation. The electrostatic interaction enables DP7-C to combine all components into a stable delivery system. In vitro and in vivo experiments confirmed that each ingredient of DMP@mgel exhibits their respective functions such as neovascularization promotion, Hippo pathway inhibition, and antioxidation capability. Finally, administration of DMP@mgel in I/R injured rats significantly improved heart function while reducing fibrosis as evidenced by echocardiography results along with Evans blue staining and histological examination.
研究领域:
心脏病学
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再生医学
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生物材料科学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-16
·
IF 14.7
Zhuang Tao,Chen Mei-Hua,Wu Ruo-Xi,Wang Jing,Hu Xi-De,Meng Ting,Wu Ai-Hua,Li Yan,Yang Yong-Feng,Lei Yu,Hu Dong-Hua,Li Yan-Xiu,Zhang Li,Sun Ai-Jun,Lu Wei,Zhang Guan-Nan,Zuo Jun-Li,Ruan Cheng-Chao
Cardiac macrophage contributes to the development of cardiac fibrosis, but factors that regulate cardiac macrophages transition and activation during this process remains elusive. Here we show, by single-cell transcriptomics, lineage tracing and parabiosis, that cardiac macrophages from circulating monocytes preferentially commit to macrophage-to-myofibroblast transition (MMT) under angiotensin II (Ang II)-induced hypertension, with accompanying increased expression of the RNA N6-methyladenosine demethylases, ALKBH5. Meanwhile, macrophage-specific knockout of ALKBH5 inhibits Ang II-induced MMT, and subsequently ameliorates cardiac fibrosis and dysfunction. Mechanistically, RNA immunoprecipitation sequencing identifies interlukin-11 (IL-11) mRNA as a target for ALKBH5-mediated m6A demethylation, leading to increased IL-11 mRNA stability and protein levels. By contrast, overexpression of IL11 in circulating macrophages reverses the phenotype in ALKBH5-deficient mice and macrophage. Lastly, targeted delivery of ALKBH5 or IL-11 receptor α (IL11RA1) siRNA to monocytes/macrophages attenuates MMT and cardiac fibrosis under hypertensive stress. Our results thus suggest that the ALKBH5/IL-11/IL11RA1/MMT axis alters cardiac macrophage and contributes to hypertensive cardiac fibrosis and dysfunction in mice, and thereby identify potential targets for cardiac fibrosis therapy in patients.
研究领域:
心脏病学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2024
·
IF 6.1
Fan Wu,Fuer Lu,Hui Dong,Meilin Hu,Lijun Xu,Dingkun Wang
Oxyberberine (OBB), a natural metabolite of berberine, has been shown to exhibit inhibitory effects on gluconeogenesis in our previous work. This work was designed to investigate the potential effects and underlying mechanisms of OBB on hepatic gluconeogenesis. Our work found that OBB significantly inhibited the expressions of glucose 6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), and decreased the glucose production in palmitic acid-induced HepG2 cells. Then, AMPK/Akt/FoxO1 and AMPK/CRTC2 signaling pathways were confirmed by transcriptomics and network pharmacology analyses. It was shown that AMPK activation may phosphorylate and promote nuclear exclusion of FoxO1 and CRTC2, two key regulators of hepatic gluconeogenesis transcriptional pathways, resulting in the inhibition of gluconeogenesis under OBB administration. Afterwards, AMPK/Akt/FoxO1, AMPK/CRTC2 signaling pathways were evidenced by western blot, immunoprecipitation and confocal immunofluorescence, and the targeted inhibitor (Compound C) and siRNA of AMPK were applied for further mechanism verification. Moreover, it was found that OBB treatment activated AMPK/Akt/FoxO1 and AMPK/CRTC2 signaling pathways to decrease hepatic gluconeogenesis in db/db mice. Similarly, the in vivo inhibitory effects of OBB on gluconeogenesis were also diminished by AMPK inhibition. Our work demonstrated that OBB can inhibit hepatic gluconeogenesis in vitro and in vivo, and its underlying mechanisms were associated with AMPK-mediated suppression of FoxO1 and CRTC2 signaling axes.
研究领域:
药理学
·
分子生物学
·
代谢
·
内分泌学
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产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2024
·
IF 2.7
Jiamin Wang,Hao Lin,Mengli Liu,Bo Xiong,Dingyuan He,Jiasheng Tu,Dongsheng He
Cationic polymers are a class of promising carriers for nucleic acid delivery. However, the balance between biosafety and transfection efficiency is still a major obstacle for nucleic acid delivery. Accurate structural design can effectively evaluate the relationship between structural factors and nucleic acid delivery. Previous series of vectors optimized based on artificial amino acid Stp have been shown to effectively improve gene transfection. Here, a series of sequenced-defined oligomers containing hydrophobic oleic acid with different topologies, different charge densities and with or without crosslinking cystine domains were designed and synthesized for a better understanding of the structure activity relationship. The oligomers were further mixed with either pDNA or siRNA to form polyplexes. The particle size, zeta potential, polyplexes formation properties, in vitro stability and reductive responsiveness of the polyplexes were investigated. In addition, studies regarding the transfection efficiency, cellular uptake, cellular trafficking, cytotoxicity and hemolysis were performed. The resulting oligomers display general good complexation ability with pDNA and siRNA with enhanced stability and redox sensitivity. some of the oligomers showed adequate or surpassed transfection efficiency compared with PEI. The polyplexes formed with oligomer #1 have good cellular uptake and endo-lysosome escape property. In addition, all the oligomers and the polyplexes showed low cytotoxicity and hemolysis, demonstrated high biocompatibility. In summary, the results evidenced that proper charge density with hydrophobic oleic acid and thiol crosslinking cystine improves the overall performance of delivering pDNA and siRNA.
研究领域:
生物医学工程
·
药学
·
分子生物学
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
Nano Today
·
2024
·
IF 13.2
Di Nie,Yishan Lv,Duo Gao,Anqi Xu,Qinyu Li,Jiaxin Li,Xiang Lu,Bingqi Wang,Jie Wang,Chang Liu,Zhuan Zhang,Xiang Li,Ning Wang,Shiyan Guo,Chunliu Zhu,Miaorong Yu,Yong Gan
Achieving efficient and secure cytosolic delivery is crucial for RNA therapeutics. Presently, delivery systems predominantly attain cytosolic release through membrane rupture or destabilization of late endosomes and lysosomes. However, these approaches lead to restricted RNA release and undesirable cytotoxicity, ultimately diminishing therapeutic efficacy. Herein, we proposed an efficient strategy based on early endosome fusion-mediated release, employing probiotic-derived lipopolysaccharide (LPS)-incorporated vesicles to enhance RNA delivery. The LPS is derived from Escherichia coli Nissle 1917 (EcN) and has a high safety confirmed by the authoritative pyrogen test. The LPS-rich outer membrane vesicles (OMVs) and synthetic chimeric liposomes (LPS-Lips) are found capable of efficient cytosolic RNA delivery by using LPS to fuse with early endosomes, as evidenced by super-resolution and real-time imaging. The OMVs and LPS-Lips (containing 10 % and 30 % EcN-derived LPS) exhibit enhanced ability to deliver functional BCL-xL siRNA, leading to more significant gene silencing and cell apoptosis in comparison to the commercial Lipofectamine 2000 and RNAiMAX groups. The in vivo results demonstrate their superior efficacy on inhibiting tumor growth and prolonged survival time with enhanced safety. These findings highlight the early endosome fusion strategy with facilitated release efficiency and safety, offering guidelines for the rational design of enhanced RNA delivery systems.
研究领域:
药学
·
分子生物学
·
癌症研究
·
生物技术
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Dan Song,Yuan Liu,Kehui Wu,Manting Lyu,Yongshu Wu,Yanan Zhang,Panling Wang,Xiangchen Li
The present study sought to investigate the protective effect of Lycopene (LYC) on Bisphenol A (BPA)-induced lipid accumulation and elucidate the potential molecular mechanism. In vitro, the PK15 cells with or without LYC were exposed to BPA for 6 h to detect the lipid accumulation using Nile red’s and Oil Red O’ staining. Meanwhile, redox status, mitochondrial function, gene expression and protein levels relating to lipid accumulation were evaluated by cellular biochemical assays, immunofluorescence staining, quantitative real-time PCR (qRT-PCR) and Western blot, respectively. In addition, ROS scavenger N-acetylcysteine (NAC), SIRT1 inhibitor EX527, SIRT1 siRNA and PGC-1α siRNA were used to verify the target signaling pathways responsible for the protective effect of LYC against BPA-indcued lipid accumulation. In vivo, the twenty four male Wistar rats were randomly divided into three groups, received either BPA (50 mg/kg/day BW) or LYC (10 mg/kg/day BW) orally for 60 days. The kidney tissues were evaluated by HE’s and Oil Red O’s staining, lipid-associated genes and proteins expression were detected through qRT-PCR and Western blot. The results showed that BPA-exposed PK15 cells and rats had increased lipid droplets with elevated transcription of lipogenic factors SREBP1 and PPARγ, and down-regulated PPARα expression, and which is accompanied by redox imbalance and abnormal mitochondrial function. Conversely, LYC prevented BPA-induced lipid metabolism disorder and lipid accumulation through impeding ROS overproduction. Moreover, PK15 cells and rats exposed to BPA showed decrease in SIRT1 and PGC-1α levels, whereas LYC blocked the decrease of SIRT1 and PGC-1α protein levels. Furthermore, inhibition or silence of SIRT1 and PGC-1α abrogated the improvements of LYC on ROS generation, mitochondrial mass impairement and lipid accumulation in BPA-treated PK15 cells. Collectively, these findings indicate that SIRT1/PGC-1α signaling pathway is involved in the protective effect of LYC on BPA-induced lipid accumulation. These results also provide a potential promising therapeutic of LYC against BPA-induced lipid accumulation in kidney cells and organs.
研究领域:
药理学
·
细胞生物学
·
分子生物学
·
毒理学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Bei Wang,Hao Cheng,Zhongsheng Ji,Zijun Jiang,Rong Wang,Yang Ding,Jiang Ni
Collaboration of cancerous cells and microenvironment is the root for tumor spreading, leading to difficulty in complete metastasis blockage via mono-intervention. Herein, a triple-responsive nanoassembly is designed for orienting tumor cells and migration-driving M2 tumor associated macrophages (TAMs) in microenvironment for efficient anti-metastatic therapy. Structurally, a reactive oxygen species (ROS)-responsive crosslinked short-chain polyquaternium is synthesized to bridge graphene oxide (GO) scaffold with apolipoprotein A-I crown via borate-crosslinking, electrostatic adherence, and coordinative coupling. The protein-crowning polymeric GO nanoparticles could give multimodal shielding and triple-responsive release of doxorubicin and Snail-targeted siRNA. Tailor-made apolipoprotein A-I crown fulfills nanoparticles synergistically attacking tumor cells and M2 TAMs via binding with overexpressed scavenger receptors. The findings witness the targeted accumulation and potent cytotoxicity of the hybrid nanoparticles for M2 TAMs and tumor cells; especially, elimination of M2 TAMs in tumor microenvironment holds back Snail-enhancing transforming growth factor (TGF)-β signal pathway, which collaborates with Snail silencing in tumor cells to reverse epithelial mesenchymal transition (EMT) and metastasis-promoting niche. Collectively, the synergistic targeting therapeutic platform could provide a promising solution for metastatic tumor treatment.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
癌症生物学
✓ 已验证
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）