JOURNAL OF NANOBIOTECHNOLOGY
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2021
·Vol. 19
·期 1
·1-21
·
IF 10.435
Guo Shiqi,Liang Yanzi,Liu Lanze,Yin Miaomiao,Wang Aiping,Sun Kaoxiang,Li Youxin,Shi Yanan
Background The use of drug nanocarriers to encapsulate drugs for oral administration may become an important strategy in addressing the challenging oral absorption of some drugs. In this study—with the premise of controlling single variables—we prepared model nanoparticles with different particle sizes, surface charges, and surface hydrophobicity/hydrophilicity. The two key stages of intestinal nanoparticles (NPs) absorption—the intestinal mucus layer penetration stage and the trans-intestinal epithelial cell stage—were decoupled and analyzed. The intestinal absorption of each group of model NPs was then investigated.Results Differences in the behavioral trends of NPs in each stage of intestinal absorption were found to result from differences in particle properties. Small size, low-magnitude negative charge, and moderate hydrophilicity helped NPs pass through the small intestinal mucus layer more easily. Once through the mucus layer, an appropriate size, positive surface charge, and hydrophobic properties helped NPs complete the process of transintestinal epithelial cell transport.Conclusion sTo achieve high drug bioavailability, the basic properties of the delivery system must be suitable for overcoming the physiological barrier of the gastrointestinal tract.
研究领域:
药学
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纳米技术
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生物药剂学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Yajun Liu,Rui Dai,Qiuyu Wei,Wenzhe Li,Guang Zhu,Hao Chi,Zhaoming Guo,Li Wang,Changhao Cui,Jianqiang Xu,Kun Ma
Janus nanoparticles with an anisotropic feature concentrated multiple properties on a single carrier, providing synergistic effects. In this study, dual-functionalized Janus nanoparticles (HA-JMSN/DOX-DMMA) were constructed with a tumor-targeting ligand (hyaluronic acid, HA) modified on the one side and a charge reversal group (2,3-dimethylmaleic anhydride, DMMA) on the other side. The drug release of HA-JMSN/DOX-DMMA was positively correlated with the acidity of the environment. The cytotoxicity and cell uptake of HA-JMSN/DOX-DMMA were superior to the isotropous nanoparticles. The endocytosis pathway of HA-JMSN/DOX-DMMA involved the clathrin-mediated endocytosis (HA) and the micropinocytosis (DMMA) at the same time, which indicated that they both participated in the interaction between nanoparticles and tumor cells. After being injected intravenously in mice, the distribution of HA-JMSN/DOX-DMMA in tumor was enhanced significantly. The antitumor therapy study in vivo showed that HA-JMSN/DOX-DMMA inhibited tumor growth and improved the survival rate of tumor-bearing mice effectively. In general, HA-JMSN/DOX-DMMA could take the synergistic effect of active targeting and charge reversal to deliver drug in tumor cells and kill them efficiently, which was a promising antitumor nanodrug.
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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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Small
·
2025
·
IF 12.1
Dan Li,Gaoyang Yi,Guifang Cao,Adam C. Midgley,Yongli Yang,Dan Yang,Wenguang Liu,Yujuan He,Xiaolin Yao,Guoliang Li
The utilization of plant-derived exosome-like nanovesicles (ELNs) as nanocarriers for oral delivery of bioactives has garnered significant attention. However, their distinctive lipid membrane composition may result in elevated membrane permeability within the gastrointestinal environment, leading to the leakage of carried bioactives. Inspired by the concept of projectile design, Tartary buckwheat-derived ELNs (TB-ELNs) based dual-carriers are fabricated by loading chlorogenic acid (CGA) into the cores and bonding selenium nanoparticles (SeNPs) to the lipid membrane. The results indicate that SeNPs bond markedly augments the membrane rigidity, and therefore enhances the stability of TB-ELNs and the retention rate of the loaded CGA during gastrointestinal digestion. In vitro and in vivo studies indicates that the TB-ELNs based dual-carriers are internalized by epithelial cells and transcytosis via the endoplasmic reticulum, and show the synergistic regulatory effect on high-fat diet-induced hyperglycemia in the intestine-liver axis. These results may be attributed to the fact that SeNPs combination reduces the gastrointestinal degradation of the carried bioactives. Moreover, SeNPs with antioxidant property can protect ELNs and their carried bioactives from oxidative damage, thereby enhancing their biological activities. Collectively, this study offers a new strategy to develop highly efficient oral delivery systems for bioactives to alleviate hyperglycemia and diabetes.
研究领域:
食品科学
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生物医学工程
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营养学
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产品关联
DOI
PubMed
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2016
·Vol. 100
·期 11
·5079-5088
·
IF 3.376
Liu Di,Guo Hua,Zheng Wenyun,Zhang Na,Wang Tianwen,Wang Ping,Ma Xingyuan
Heat-labile enterotoxin (LT) is a protein toxin produced by enterotoxigenic Escherichia coli (ETEC). As a bacterial toxin, LT holotoxin can enter intestinal epithelial cells and cause diarrhea. In addition, LT is also a powerful mucosal adjuvant capable of enhancing the strong immune responses to co-administered antigens. However, the LT immunological mechanism is still not clear in some aspects, especially with the respect to how the LTA subunit functions alone. Here, we discovered that the A 2 domain of LTA could carry a fluorescent protein into cells, whose function is similar to a cell-penetrating peptide. The transmembrane-transporting ability of the A 2 domain is non-specific in its cell-penetrating function, which was shown through testing with different cell types. Moreover, the LTA 2 fusion protein penetrated a fluorescently labeled cell membrane that identified LTA 2 internalization through membrane transport pathways, and showed it finally localized in the endoplasmic reticulum. Furthermore, low-temperature stress and pharmacological agent treatments showed that the LTA 2 internalization route is a temperature-dependent process involving the clathrin-mediated endocytosis and the macropinocytosis pathways. These results could explain the internalization of the LTA subunit alone without the LTB pentamer, contributing to a better understanding of LTA working as a mucosal adjuvant; they also suggest that the A 2 domain could be used as a novel transport vehicle for research and treatment of disease.
研究领域:
微生物学
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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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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2020
·
IF 4.321
Xinyi Tan,Na Yin,Zixu Liu,Rong Sun,Jingxin Gou,Tian Yin,Yu Zhang,Haibing He,Xing Tang
The oral delivery of macromolecules using nanoparticles is limited by secreted mucus, resulting in low contact or internalization via intestinal cells and, thus, both mucus trapping and further low cellular uptake need to be overcome. Here, hydrophilic and electroneutral nanoparticles were developed to overcome mucus trapping and enhance the oral delivery of macromolecules. Mesoporous silica nanoparticles (MSNs) were synthesized and modified with a hydrophilic block polymer (poly(lactic acid)–methoxy poly(ethylene glycol), PLA–PEG), and then an overall electroneutrality and promoted cellular uptake were achieved by sequential modification with cell-penetrating peptides (CPPs). Reduced hydrophobic and electrostatic interactions of MSN@PLA–PEG-CPP with mucus decreased mucus trapping by 36.0%, increased the cellular uptake of MSN@PLA–PEG-CPP by 2.3-folds in mucous conditions via active heparan sulfate proteoglycan receptor (HSPG)-mediated and caveolae-mediated endocytosis and electrostatic interactions. Furthermore, insulin, a model macromolecular drug, was successfully loaded into the nanoparticles (INS@MSN@PLA–PEG-CPP). Compared with insulin solution, in vitro cellular uptake in mucous conditions and in vivo pharmacodynamic effects were significantly increased by 9.1- and 14.2-folds, respectively. As well, all nanoparticles with or without insulin loading presented negligible in vitro and in vivo toxicity. Herein, hydrophilic and electroneutral nanoparticles with sequential PEG and CPP modification could promote cellular uptake against mucus trapping and finally show good prospects for oral insulin delivery.
研究领域:
药剂学
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生物医学工程
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材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Xiudan Wang,Junya Lu,Yuling Mao,Qinfu Zhao,Caishun Chen,Jianan Han,Meiqi Han,Huijuan Yuan,Siling Wang
The accumulation of nanomedicines in tumor tissues determines their therapeutic efficacy. We herein exploit the tropism of macrophages to improve the accumulation and retention time of nanomedicine at tumors. Interestingly, macrophages are not merely as transporters, but killers activated by nanomedicine. The system( [email protected] /ICG) was established by decorating macrophages with hyaluronic acid-modified hollow mesoporous carbon (C) nanoparticles loading indocyanine green (ICG). Notably, C nanoparticles with superior photothermal conversion capability not merely guarantee the efficient delivery of ICG through high drug loading efficiency and inhibiting the premature leaky, but effectually activate the polarization of macrophages. The results exhibited that those activated macrophages could release pro-inflammatory cytokines (NO, TNF-α, IL-12), while [email protected] /ICG afforded about 2-fold higher tumor accumulation compared with pure nanoparticle C-HA/ICG and produced heat and singlet oxygen ( 1 O 2 ) under irradiation of an 808 nm laser , realizing the combination of photodynamic therapy (PDT), photothermal therapy (PTT) and cytokines-mediated immunotherapy . Specially, we also investigated the relationship of singlet oxygen ( 1 O 2 ) or temperature and tumor-killing activity for understanding the specific effectual procedure of PDT/PTT synergistic therapy. Overall, we firstly established an “all active” delivery system integrating the features of nanomedicine with biological functions of macrophages, providing a novel insight for cell-mediated delivery platform and tumor targeted multimodality anti-cancer therapy.
研究领域:
纳米技术
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癌症治疗
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免疫学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
·
2022
·Vol. 49
·期 8
·2655-2667
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IF 10.057
Hou Zhenyu,Zhou Mei,Ma Yuanyuan,Xu Xiaoxuan,Zhang Zhiqi,Lai Shiwei,Fan Wenpei,Xie Jinbing,Ju Shenghong
Purpose Radiation therapy (RT) and photodynamic therapy (PDT) are promising while challenging in treating tumors. The potential radiation resistance of tumor cells and side effects to healthy tissues restrict their clinical treatment efficacy. Effective delivery of therapeutic agents to the deep tumor tissues would be available for tumor-accurate therapy and promising for the tumor therapy. Thus, developing nanoprobes with effectively delivering radiotherapy sensitizers and photosensitizers to the interior of tumors is needed for the accurate combined RT and PDT of tumor. Methods The size-changeable nanoprobes of Gd 2 O 3 @BSA-BSA-Ce6 (BGBC) were synthesized with a crosslinking method. Magnetic resonance imaging (MRI) and in vivo near-infrared (NIR) imaging were measured to evaluate the nanoprobes’ tumor accumulation and intratumor penetration effect. The tumor suppression effect of combined RT and PDT with these nanoprobes was also studied for the 4T1 bearing Balb/c mice. Results The nanoprobes BGBC showed high tumor accumulation and disintegrated into small particles responding to the photo-irradiation-produced reactive oxygen species (ROS), allowing for tumor penetration. Abundant radiotherapy sensitizers and photosensitizers were delivered to the deep tumor tissues, which is available for the accurate therapy of tumor. In addition, the BGBC displayed outstanding MRI and fluorescence imaging effects for evaluating the biodistribution and tumor suppression effect of nanoprobes. Consequently, significant tumor suppression effect was obtained based on the accurate tumor treatment with the combined RT and PDT. Conclusion The designed size-changeable nanoprobes BGBC showed excellent tumor accumulation and deep tumor penetration, resulting in a significant tumor suppression effect based on the combined RT and PDT. This study provides a novel strategy for dual delivery of radiotherapy sensitizers and photosensitizers into the deep tumor tissues and is promising for the accurate theranostics of tumor.
研究领域:
癌症治疗
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放射医学
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纳米医学
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医学影像
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Mingming Song,Shuqi Dong,Xiaofei An,Wenxiang Zhang,Ning Shen,Yanbo Li,Caixia Guo,Chang Liu,Xiao Li,Siyu Chen
Chemotherapy is a difficult treatment for cancer patients because of the low effective accumulation of chemo-drugs and their detrimental side effects. Nanoparticles have shown promise as a solution to these problems. However, the known differences in the porosity and vascularization of tumor vessels, and other factors, including the potential formation of a “protein crown,” the short half-life time in circulation, and the low drug distribution, often limit their application. To address these problems, biomimetic nanoparticles coated with cell membranes have been developed and shown to have advantages such as prolonged circulation, high biocompatibility, and enhanced targeting abilities in drugs and nanoparticles, thus exhibiting good application prospects in cancer therapy for liver, lung, and melanoma cancers. Accordingly, we designed a PH-sensitive biomimetic nanodrug delivery system with a delicate “core–shell” structure based on red blood cell membranes. Briefly, core nanoparticles were synthesized by the self-assembly of natural amphoteric polymers, including hydrophilic carboxymethylcellulose sodium and hydrophobic stearic acid . For the shell structure, red blood cell membranes were modified using folic acid by a lipid tether (1,2-distearoyl-sn-glycero-3-phosphoethanolamine) to increase tumor-targeting ability, whereas polyethylene glycol was inserted to decrease lipid tether modification-induced potential sequestration by either the mononuclear phagocyte system or the reticuloendothelial system. Via a series of formulation optimizations, paclitaxel was packaged into the red blood membrane-based core–shell nanoparticles with an average size of 226.9 ± 2.75 nm and a negative Zeta potential of −14.5 ± 0.3 mV. More importantly, the examinations focusing on CD47, a representative red blood cell membrane protein, revealed not only the successful establishment of the membrane shell but also the right-side-out membrane orientation on our core–shell nanoparticles. Our nanodrug delivery system showed good biocompatibility and sensitivity to acidic tumor microenvironments while effectively prolonging the circulation time of paclitaxel and further enhancing its antitumor effects on epithelial malignancies, including liver, lung, and melanoma cancers. In particular, our nanodrug delivery system significantly alleviated paclitaxel-induced renal toxicity . Taken together, our findings highlight that the red blood membrane-based core–shell nanoparticle is a promising biomimetic nanodrug delivery system for functionally delivering chemotherapeutic drugs, and it has promise in clinical applications.
研究领域:
药学
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纳米技术
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肿瘤学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2021
·
IF 7.514
Zhuqing Dai,Jiangfeng Song,Ye Chen,Lei Feng,Yayuan Xu,Dajing Li,Caie Wu,Zhongyuan Zhang,Jun Liu
This study aims to develop novel lutein nanoparticles encapsulized by stevioside (LUT-STE, 165 ± 2 nm average particles size) and systematically evaluate its bioavailability. Multiple spectroscopy and NMR analyses showed lutein and stevioside could interact through hydrogen bonds, C H π interaction and van der Waals forces. Molecular docking simulation showed lutein was well distributed in the hydrophobic cavity of stevioside. Analyzed by Caco-2 cellular models, the transported amount of LUT-STE was 2.39 times that of lutein in 120 min with a P app (B → A)/ P app (A → B) value of 0.63 ± 0.04. Nystatin and dynasore significantly reduced the cellular uptake of LUT-STE by 41.3% and 57.7%, respectively. Compared with free lutein, LUT-STE increased the C max in mice plasma by 5.01-fold and promoted the accumulation in multiple organs. LUT-STE promoted the protein expressions of CD36, NPC1L1 and PPARγ in both cell and animal models. In conclusion, stevioside entrapment significantly promote the bioavailability of lutein through multiple transmembrane pathways.
研究领域:
药学
·
营养学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2021
·
IF 6.419
Mingming Song,Wentao Xia,Zixuan Tao,Bin Zhu,Wenxiang Zhang,Chang Liu,Siyu Chen
Malignant melanoma is a life-threatening form of skin cancer with a low response rate to single-agent chemotherapy. Although combined therapies of metformin (MET) and doxorubicin (DOX) are effective in treating a variety of cancers, including breast cancer, their different physicochemical properties and administration routines reduce the effective co-accumulation of both drugs in tumors. Nanoparticles (NPs) have been demonstrated to potentially improve drug delivery efficiency in cancer therapy of, for example, liver and lung cancers. Hence, in this study, we prepared pH-sensitive, biocompatible, tumor-targeting NPs based on the conjugation of biomaterials, including sodium alginate, cholesterol, and folic acid (FCA). As expected, since cholesterol and folic acid are two essentials, but insufficient, substrates for melanoma growth, we observed that the FCA NPs specifically and highly effectively accumulated in xenograft melanoma tumors. Taking advantage of the FCA NP system, we successfully co-delivered a combination of MET and DOX into melanoma tumors to trigger pyroptosis, apoptosis, and necroptosis (PANoptosis) of the melanoma cells, thus blocking melanoma progression. Combined, the establishment of such an FCA NP system provides a promising vector for effective drug delivery into melanoma and increases the possibility and efficiency of drug combinations for cancer treatment.
研究领域:
癌症治疗
·
纳米技术
·
药学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Yu Zhang,Junxi Liu,Pengfei Dou,Zhijing Wu,Ziming Zheng,Xianglin Pan,Tao Zhou,Kaiping Wang
The elucidation of the oral absorption of natural polysaccharides contributes to their further research and utilization. Herein, to explore the absorption of a pectin-type polysaccharide from Smilax china L. (SCLP), SCLP was respectively fluorescently labeled with fluorescein-5-thioicarbazide (FSCLP) and Cyanine7 amine (Cy7-SCLP) for in vitro and in vivo tracking. The near-infrared imaging demonstrated that Cy7-SCLP was absorbable in the small intestine and distributed in the liver and kidney after oral administration. Subsequently, in vitro intestinal epithelial tissue experiments showed that the jejunum was the dominant site of FSCLP transport. Further transport studies in the Caco-2 cell monolayer illustrated that FSCLP was delivered across the monolayer via transcellular transport by caveolae-mediated endocytosis and macropinocytosis together with paracellular transport by reversibly affecting tight junctions. In summary, this work presents the oral absorption characteristics and mechanisms of SCLP through the intestinal epithelium, which will facilitate the further development of SCLP and pectin polysaccharides.
研究领域:
药理学
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营养学
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生物学
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生物技术
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Therapy-Nucleic Acids
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2023
·
IF 8.8
Xin Chang,Chang Liu,Yu-Mo Han,Qiu-Ling Li,Bin Guo,Hu-Lin Jiang
Pulmonary fibrosis (PF) is an interstitial lung disease with complex pathological mechanism, and there is currently a lack of therapeutics that can heal it completely. Using gene therapy with drugs provides promising therapeutic strategies for synergistically reversing PF. However, improving the intracellular accumulation and transfection efficiency of therapeutic nucleic acids is still a critical issue that urgently needs to be addressed. Herein, we developed lipid nanoparticles (PEDPs) with high transfection efficiency coloaded with pDNA of nuclear factor erythroid 2-related factor 2 (pNrf2) and pirfenidone (PFD) for PF therapy. PEDPs can penetrate biological barriers, accumulate at the target, and exert therapeutic effects, eventually alleviating the oxidative stress imbalance in type II alveolar epithelial cells (AECs II) and inhibiting myofibroblast overactivation through the synergistic effects of Nrf2 combined with PFD, thus reversing PF. In addition, we systematically engineered various liposomes (LNPs), demonstrated that reducing the polyethylene glycol (PEG) proportion could significantly improve the uptake and transfection efficiency of the LNPs, and proposed a possible mechanism for this influence. This study clearly reveals that controlling the composition ratio of PEG in PEDPs can efficiently deliver therapeutics into AECs II, improve pNrf2 transfection, and synergize with PFD in a prospective strategy to reverse PF.
研究领域:
药理学
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分子生物学
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基因治疗
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肺科学
✓ 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）