International Journal of Nanomedicine
·
2023
·
IF 8
Kai Yue,Chao Yang,Yu You,Xueying Wang,Xinxin Zhang
Background A good understanding of the adhesion behaviors of the nanocarriers in microvessels in chemo-hyperthermia synergistic therapy is conducive to nanocarrier design for targeted drug delivery.Methods In this study, we constructed an artificial blood vessel system using gelatins with a complete endothelial monolayer formed on the inner vessel wall. The numbers of adhered NPs under different conditions were measured, as well as the interaction forces between the arginine–glycine–aspartic acid (RGD) ligands and endothelial cells.Results The experimental results on the adhesion of ligand–coated nanoparticles (NPs) with different sizes and morphologies in the blood vessel verified that the gelatin-based artificial vessel possessed good cytocompatibility and mechanical properties, which are suitable for the investigation on NP adhesion characteristics in microvessels. When the temperature deviated from 37 °C, an increase or decrease in temperature resulted in a decrease in the number of adhered NPs, but the margination probability of NP adhesion increased at high temperatures due to the enhanced Brownian movement and flow disturbance. It is found that the effect of cooling was less than that of heating according to the observed changes in cell morphology and a decrease in cell activity under the static and perfusion culture conditions within the temperature range of 25 °C–43 °C. Furthermore, the measurement results of change in the RGD ligand-cell interaction with temperature showed good agreement with those in the number of adhered NPs.Conclusion The Findings suggest that designing ligands that can bind to the receptor and are least susceptible to temperature variation can be an effective means to enhance drug retention.
研究领域:
生物医学工程
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纳米医学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2018
·
IF 3.789
Weifeng Lin,Guanglong Ma,Zhefan Yuan,Haofeng Qian,Liangbo Xu,Elie Sidransky,Shengfu Chen
Much attention has been drawn to targeted nanodrug delivery systems due to their high therapeutic efficacy in cancer treatment. In this work, doxorubicin (DOX) was incorporated into a zwitterionic arginyl–glycyl–aspartic acid (RGD)-conjugated polypeptide by an emulsion solvent evaporation technique with high drug loading content (45%) and high drug loading efficiency (95%). This zwitterionic nanoformulation showed excellent colloidal stability at high dilution and in serum. The pH-induced disintegration and enzyme-induced degradation of the nanoformulation were confirmed by dynamic light scattering and gel permeation chromatography. Efficient internalization of DOX in the cells and high antitumor activity in vitro was observed. Compared with the free drug, this nanoformulation showed higher accumulation in tumor and lower systemic toxicity in vivo. The DOX-loaded zwitterionic RGD-conjugated polypeptide vesicles show potential application for targeted drug delivery in the clinic.
研究领域:
药学
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肿瘤学
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生物材料科学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2017
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IF 7.504
Yongjing Li,Jiaxun Wan,Zihao Zhang,Jia Guo,Changchun Wang
The development of multifunctional ultrasound contrast agents has inspired considerable interest in the application of biomedical imaging and anticancer therapeutics. However, combining multiple components that can preferentially accumulate in tumors in a nanometer scale poses one of the major challenges in targeting drug delivery for theranostic application. Herein, reflux-precipitation polymerization, and N-(3-(dimethylamino)propyl)-N′-ethylcarbodiimide-meditated amidation reaction were introduced to effectively generate a new type of soft glycine/poly(ethylene glycol) (PEG)/RGD-modified poly(methacrylic acid) nanobubbles with a uniform morphology and desired particle size (less than 100 nm). Because of the enhanced biocompatibility resulting from the glycine modification, over 80% of the cells survived, even though the dosage of glycine-modified polymeric nanobubbles was up to 5 mg/mL. By loading doxorubicin as an anticancer drug and perfluorohexane as an ultrasound probe, the resulting glycine/PEG/RGD-modified nanobubbles showed remarkable cancer therapeutic efficacy and a high quality of ultrasonic imaging; thus, the ultrasonic signal exhibited a 1.47-fold enhancement at the tumor site after intravenous injection. By integrating diagnostic and therapeutic functions into a single nanobubble, the new type of theranostic nanobubbles offers a promising strategy to monitor the therapeutic effects, giving important insights into the ultrasound-traced and enhanced targeting drug delivery in biomedical applications.
研究领域:
生物医学工程
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药学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Polymer Materials
·
2025
·
IF 4.7
Jinxuan He,Zhixiang Mou,Lan Chen,Qixian Chen,Xuduan Chen,Lixin Wei
Secondary hyperparathyroidism is driven by pathological overproduction of parathyroid hormone. Surgery is invasive, drug therapy offers only transient control, and both carry substantial side effects. Previous efforts to deliver siRNA to the parathyroid glands achieved only marginal efficacy because the constructs lacked a targeting ligand to overcome the organ’s limited vascular permeability and were rapidly cleared by renal filtration. This study provides a targeted RNA interference therapeutic strategy for treatment of secondary hyperparathyroidism by leveraging the angiogenic characteristics of parathyroid glands via systemic route. Particularly, we manufactured an Arg-Gyl-Asp (RGD)-conjugated siRNA delivery system that exploits the overexpression of integrins and increased vascular permeability in parathyroid glands to achieve preferential siRNA accumulation. The multifunctional cationic copolymers of RGD-poly(ethylene glycol) (PEG)-polylysine-azido [PLys(N3)] and PLys(ss-dibenzocyclooctyne: DBCO) were synthesized and characterized, demonstrating their ability to formulate robust nanocomplexes with small interference RNA [(siRNA): knockdown of parathyroid hormone (PTH)] by virtue of favorable reversible disulfide cross-linking (based on click reaction) post electrostatic complexation. These nanocomplexes exhibited prolonged systemic circulation, preferential accumulation in the angiogenic parathyroid glands, and active intracellular delivery, leading to significant suppression of PTH expression. In a parathyroid hyperplasia mouse model, the siPTH delivery construct from RGD–PEG-PLys(N3)&PLys(ss-DBCO) substantially reduced the serum PTH levels to near-normal values, highlighting the therapeutic potential of our siRNA delivery system. Hence, this RNAi approach outperforms conventional modalities by achieving rapid, potent, and sustained gene knockdown without surgical risk or chronic pharmacologic burden, establishing a paradigm for precision endocrine therapy.
研究领域:
分子生物学
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内分泌学
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纳米医学
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基因治疗
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药理学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 10
·期 3
·384-395
·
IF 6.331
Juan Liu,Xixue Hu,Shubin Jin,Xing-Jie Liang,Xiaowei Ma
Rapid release and clearance of antitumor drugs in vivo are the main factors used to evade the effectiveness of chemotherapeutics. Targeted delivery and controlled release of drugs are the most pressing dilemmas in cancer therapy. Herein we report the design and fabrication of multifunctional mesoporous silica nanoparticles coated with poly(N-isopropylacrylamide)-co-acrylic acid and calcium phosphate (MSCNs) with pH-triggered chemotherapeutic release and dual-targeting functions. By decorating the nanoparticle surface with a transferrin (Tf)/RGD ligand, these nanoparticles are capable of not only recognizing the intrinsic pH difference between tumor and normal tissues, but also targeting the lesion location. It was shown that Tf/RGD-MSCNs delivered the anti-tumor drug doxorubicin more efficiently into lysosomes and the resulting DOX-loaded nanoparticles (DOX-Tf/RGD-MSCNs) showed a stronger inhibitory effect towards tumor cell growth than free DOX and DOX delivered by unmodified MSNs. Moreover, the nanoparticles are more biocompatible than uncoated mesoporous silica nanoparticles. All these results indicate that Tf/RGD-MSCNs have great potential as a novel drug carrier in therapeutic applications against cancers.
研究领域:
纳米技术
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癌症治疗
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材料科学
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2024
·
IF 3.7
Xiaokai Pan,Juan Nie,Jiacheng Lei,Peng Wang,Kaikai Zheng,Qiang Wei,Xiaojing Liu
Understanding how the spatial distribution of adhesive ligands regulates cell behavior is crucial for designing biomaterials. This study investigates how precisely controlled ligand spacing affects cell spreading and integrin subtype engagement. Using engineered polyacrylamide hydrogels with gold nanoparticle arrays, we explored the impact of RGD ligand spacings (30 and 150 nm) on human mesenchymal stromal cells. Cells exhibited distinct morphological behaviors: smaller spacings promoted larger spreading areas, while larger spacings resulted in elongated shapes with reduced spreading. Mechanistically, we found that the α5β1 integrin, not the αvβ3 integrin, played a central role in mediating these responses, alongside lamellipodia formation. Our findings provide critical insights into the spatial sensing of ligands, highlighting the influence of ligand spacing on cellular mechanotransduction and integrin-specific responses. This work advances the understanding of cell-material interactions and offers potential strategies for designing biomaterials to guide cell behavior in tissue engineering.
研究领域:
细胞生物学
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生物材料科学
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组织工程
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生物物理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2019
·
IF 4.213
Xin Jin,Jianping Zhou,Zhenhai Zhang,Huixia Lv
Synergistic combination therapy involving the integration of chemotherapeutics and chemosensitizers into micelles has demonstrated great potential for tumor-specific location release. Here, the natural product betulinic acid (BA) and chemical drug lonidamine (LN) were used as chemosensitizers in combination with doxorubicin (DOX) for ovarian cancer treatment. We designed pH-sensitive peptide derivatives and constructed an all-in-one multifunctional multidrug pH-sensitive targeting delivery system for the synergistic co-delivery of DOX and BA (or LN). The combination of DOX and BA was found to elicit better therapeutic effects and lower cardiotoxicity than the DOX and LN combination in Skvo3 cells. Further, loading DOX/BA into the present micellar systems enabled burst release at the tumor location, leading to enhanced anti-tumor effects and reduced off-target effects. More importantly, DOX/BA micelles elicited fewer adverse effects on cardiac function and leukocyte counts in Skvo3 subcutaneous xenograft models. These features suggest that the designed micelles represent a promising multifunctional strategy for the efficient treatment of ovarian cancer.
研究领域:
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Hongyan Cui,Liuwei Zhang,Shuang Zeng,Yu Wang,Zhen Li,Jingyun Wang,Qixian Chen
We have tailored multifaceted chemistries into the manufacture of artificial virus-like delivery vehicles mimicking viral “intelligent” transportation pathways through sequential biological barriers; these vehicles can acquire the ability to dynamically “program transfer” to their target sites. To accomplish this, we created anionic pro-proteins, which facilitate charge reversal when subject to acidic endosomal pH; in this way, carboxylation reactions are performed on proteins with amine-reactive cis-aconitic anhydride. Electrostatic associations then initiate the envelopment of these pro-proteins into multilayered nanoarchitectural vehicles composed of multiple-segmental block copolycationic cyclic Arg-Gly-Asp (RGD)-poly(ethylene glycol)(PEG)-GPLGVRG-polylysine(thiol). Therefore, upon the pro-proteins’ initial binding to the tumors via the protruding RGD ligands, the bio-inert PEG surroundings are detached through the enzymolysis of the intermediate GPLGVRG linkage by tumor-enriched matrix metalloproteinases, unveiling the cationic polylysine palisade and imparting intimate affinities to the anionic cytomembranes of the targeted tumors. Essentially, through their active endocytosis into the subcellular endosomal compartments, the pro-proteins are made capable of retrieving the original amine groups through a charge reversal decarboxylation process, consequently eliciting augmented charge densities (charge nonstoichiometric protein@polylysine(disulfide)) to disrupt the anionic endosomal membranes to facilitate translocation into the cytosol. Eventually, the active protein payloads can be liberated from nonstoichiometric protein@polylysine(thiol) by the disassembly of polylysine palisade upon the cleavage of disulfide crosslinking in response to the very high level of glutathione in the cytosol, thereby contributing toward extreme cytotoxic potency. Hence, our elaborated virus-mimicking platform has demonstrated potent antitumor efficacy through the systemic administration of ribonucleases, which will consequently lead to an innovative new therapeutic method by which proteins could reach intracellular targets.
研究领域:
生物医学工程
·
纳米技术
·
癌症研究
·
分子生物学
·
药物递送系统
✓ 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）