Pharmaceutics
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2024
·Vol. 16
·期 7
·936
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IF 4.9
Peng Chen,Zhihui Wang,Xinmo Wang,Junni Gong,Ju Sheng,Yufei Pan,Dandan Zhu,Xiaoxuan Liu
Small interfering RNA (siRNA) therapeutics, characterized by high specificity, potency, and durability, hold great promise in the treatment of cancer and other diseases. However, the clinic implementation of siRNA therapeutics critically depends on the safe and on–demand delivery of siRNA to the target cells. Here, we reported a family of ferrocenyl amphiphilic dendrimers (Fc-AmDs) for on–demand delivery of siRNA in response to the high ROS content in cancer cells. These dendrimers bear ROS–sensitive ferrocene moieties in the hydrophobic components and positively chargeable poly(amidoamine) dendrons as the hydrophilic entities, possessing favorable safety profiles and ROS responsive properties. One of these ferrocenyl amphiphilic dendrimers,Fc-C8-AmD 8A, outperforms in siRNA delivery, benefiting from its optimal balance of hydrophobicity and hydrophilicity. Its ROS feature facilitates specific and efficient disassembly of its complex with siRNA in ROS–rich cancer cells for effective siRNA delivery and gene silencing. Moreover,Fc-C8-AmD 8Aalso integrates the features and beneficial properties of both lipid and dendrimer vectors. Therefore, it represents a novel on–demand delivery system for cancer cell–specific siRNA delivery. This work opens new perspectives for designing self–assembly nanosystems for on–demand drug delivery.
研究领域:
药学
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纳米技术
·
癌症研究
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药物递送系统
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DOI
PubMed
高影响因子
MACROMOLECULES
·
2019
·
IF 5.997
Ke Zheng,Jie Ren,Junpo He
Amphiphilic dendrimer-like polymers are expected to be promising candidates as micro containers or carriers due to their much larger size in relative to regular dendrimers. In the present study, we synthesize amphiphilic dendrimer-like copolymers possessing interior poly(styrene) segments and peripheral poly(ethylene oxide) (PEO) segments through iterative anionic polymerization, hydrosilylation, coupling, followed by olefin cross-metathesis with a PEO macromonomer bearing acrylic terminus (denoted as PEGMEA480). The molecular weight of the resulting dendrimer-like copolymer, G3-g-PEO2900, is as large as 2.16 × 106, with number of outer PEO arms up to 2900, and the average diameter 32.8 nm in solution. The behavior of the dendritic product as unimolecular micelles is investigated, using dynamic light scattering (DLS) and pyrene probing, together with the thermal responsiveness arising from the low critical solution temperature (LCST) of PEO segments. The amphiphilic dendrimer-like copolymers are used as nanoreactors for the nucleophilic displacement of benzyl halide by KSCN and the hydrolysis reaction of benzyl halide, in which significant increases in the reaction yields are observed. More interestingly, the nanoreactor can be regulated activation-and-deactivation due to thermoresponsiveness of peripheral PEO segments, and the dendritic nanoreactor is recyclable for at least 7 times.
研究领域:
高分子化学
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材料科学
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纳米技术
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2013
·
IF 2.108
Pei Zhang,Hui Wang,Xia Liu,Xuefeng Shi,Jian Zhang,Guang Yang,Keji Sun,Jinben Wang
The dynamic surface tension and dilational viscoelasticity properties of amphiphilic polyamidoamine (PAMAM) dendrimers were investigated to probe the hydrophobic chain effect on the interfacial properties and the demulsification behaviors. The values of dynamic parameters n and t * representing diffusion speed of the molecules obtained according to the Rosen equation decreased with the increasing of bulk concentration. Taking the hydrophobic effect into consideration, the t * values decreased and n values increased with the increase of alkyl chain length, suggesting easier adsorption and faster diffusion for longer hydrophobic chain which was opposite to the tendency of traditional surfactants. Further dilational viscoelasticity studies demonstrated that the properties referring to adsorption and exchange-diffusion were probably affected by the aggregates conformation at the interface. Subsequently, from the demulsification experiments a conclusion can be drawn that the amphiphilic dendrimers with branched dendritic structure possesses superior properties of breaking W/O crude oil emulsions, showing a certain correlation to the dilational viscoelasticity properties.
研究领域:
胶体与界面化学
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石油化学
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高分子科学
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流变学
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表面活性剂化学
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DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2022
·
IF 5.395
Wei Guo,Wenchang Liu,Pengqi Wan,Hao Wang,Chunsheng Xiao,Li Chen,Xuesi Chen
Cancer has become the leading cause of human death worldwide, and there is an urgent need to design and develop new oncology drugs. In this study, we report series of cationic amphiphilic dendrons with different hydrophobic alkyl chains (Cn) and different generations (Gx) and demonstrate their use for anticancer applications. The results revealed that lower-generation dendrons (G1) with a longer hydrophobic alkyl chain (C12 and C18) have stronger antitumor activity. Among these dendrons, a lead candidate C12–G1 was identified that demonstrated excellent broad-spectrum antitumor activity in 7 cancer cell lines including highly metastatic tumor cells, while simultaneously, hemolysis was negligible. Mechanistic studies showed that C12–G1 could lead to cytoplasmic leakage and induce cancer cell necrosis through membrane disruption. In addition, C12–G1 showed potent inhibition of tumor growth in a B16–F10 melanoma model. In conclusion, these findings demonstrate that the cationic amphiphilic dendron might be a promising agent for anticancer application.
研究领域:
药学
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2023
·
IF 7.4
Xin Feng,Anton Iliuk,Xiaoye Zhang,Shengnan Jia,Ao Shen,Wenke Zhang,Lianghai Hu,W. Andy Tao
Exosomes are an emerging source for disease biomarker discovery due to the high stability of proteins protected by phospholipid bilayers. However, liquid biopsy with exosomes remains challenging due to the extreme complexity of biological samples. Herein, we introduced an amphiphile-dendrimer supramolecular probe (ADSP) for the efficient capture and high-throughput analysis of exosomes, enabling the array-based assay for marker proteins. Amphiphilic amphotericin B was functionalized onto highly branched globular dendrimers, which can then insert into the exosome membrane efficiently, forming a supramolecular complex through multivalent interactions between the probe and the bilayer of exosomes. The ADSP can be easily coated onto magnetic beads or the nitrocellulose membrane, facilitating the capture of exosomes from a minimum amount of clinical samples. The captured exosomes can be detected with target protein antibodies via Western blotting or in a high-throughput array-based dot blotting format. This new strategy exhibited excellent extraction capability from trace body fluids with superior sensitivity (less than 1 μL plasma), good quantitation ability (R2 > 0.99), and high throughput (96 samples in one batch) using clinical plasma samples. The combination of proteomics and ADSP will provide a platform for the discovery and validation of protein biomarkers for cancer diagnosis and prognosis.
研究领域:
生物标志物发现
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癌症诊断
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蛋白质组学
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纳米技术
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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 Nano Materials
·
2024
·
IF 5.3
Mei Cong,Guangxing Xie,Bingjie Wang,Qian Liu,Hao Sun,Shaoyou Yang,Feifei Li,Yongguang Zhang,Ranxu Liu,Weidong Zhao
Chemotherapy continues to be a mainstay of cancer therapy. However, the anticancer efficacy of chemotherapy drugs is greatly restricted by their side effects and resistance. Nanotechnology-based combination therapy is expected to improve chemotherapy by enhancing anticancer drug efficacy, reducing drug toxicity, and overcoming drug resistance. In this study, we developed an original nanoprodrug based on an ibuprofen-modified amphiphilic dendrimer (AIP), which could self-assemble into nanoparticles to codeliver the anticancer agent doxorubicin. Owing to the protonation of amine units in amphiphilic dendrimers, the resulting nanosystem (AIP@DOX) could control the pH-stimulated release of loaded cargos in the acidic tumor microenvironment. Importantly, AIP@DOX not only significantly facilitated the cellular uptake and retention of doxorubicin but also notably decreased the drug efflux to combat drug resistance, both of which contribute to enhanced drug potency. Moreover, the high selectivity of AIP@DOX obviously reduced doxorubicin-based toxicity and markedly prolonged the survival of the mice. Benefiting from the advantageous features of both combination therapy and nanotechnology-based drug delivery, this chemo/anti-inflammatory combination nanosystem constitutes a potent therapeutic candidate for cancer treatment. This study also highlights the promise of self-assembling amphiphilic dendrimer-based vesicles for drug delivery in combination therapy to enhance drug potency.
研究领域:
药学
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纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
DOI
高影响因子
Nature Communications
·
2021
·Vol. 12
·期 1
·1-16
·
IF 14.919
Wang Yongchao,Gong Ningqiang,Ma Chi,Zhang Yuxuan,Tan Hong,Qing Guangchao,Zhang Jimei,Wang Yufei,Wang Jinjin,Chen Shizhu,Li Xianlei,Ni Qiankun,Yuan Yuan,Gan Yaling,Chen Junge,Li Fangzhou,Zhang Jinchao,Ou Caiwen,Zhao Yongxiang,Liu Xiaoxuan,Liang Xing-Jie
Immunological adjuvants are essential for successful cancer vaccination. However, traditional adjuvants have some limitations, such as lack of controllability and induction of systemic toxicity, which restrict their broad application. Here, we present a light-activable immunological adjuvant (LIA), which is composed of a hypoxia-responsive amphiphilic dendrimer nanoparticle loaded with chlorin e6. Under irradiation with near-infrared light, the LIA not only induces tumour cell lysis and tumour antigen release, but also promotes the structural transformation of 2-nitroimidazole containing dendrimer to 2-aminoimidazole containing dendrimer which can activate dendritic cells via the Toll-like receptor 7-mediated signaling pathway. The LIA efficiently inhibits both primary and abscopal tumour growth and induces strong antigen-specific immune memory effect to prevent tumour metastasis and recurrence in vivo. Furthermore, LIA localizes the immunological adjuvant effect at the tumour site. We demonstrate this light-activable immunological adjuvant offers a safe and potent platform for in situ cancer vaccination.
研究领域:
癌症研究
·
免疫学
·
纳米技术
·
药学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）