Science China-Materials
·
2020
·Vol. 64
·期 1
·241-251
·
IF 6.098
Wu Pengkai,Yin Shuai,Liu Tianqing,Ding Dan,Wang Kaikai
Incorporating functional ligands and biodegradable bonds into biocompatible low-molecular-weight (LMW) polymers, such as 1.8 kDa poly(ethylenimine) (PEI 1.8k), is a common strategy to improve the properties of LMW polymers including biosafety and delivery efficacy. This study demonstrates the hypothesis that introducing different functional ligands and linked reductive disulfides in PEI 1.8k will achieve superior siRNA transfection efficiency. By incorporating PEI-X (X represents cholesterol (Ch), heptafluorobutyric anhydride (HFBA, F) and 4-carboxyphenylboronic acid (PBA)) functional ligands into PEI 1.8k and subsequently crosslinking with each other via disulfide bond links, reductive-responsive PEI-X-SS-X-PEI copolymers were constructed to enhance the cellular transfection via the synergistic effect of the high affinity of Ch, F and PBA to cell membranes and the disulfide reduction triggered intracellular disassembly of micelles and subsequent siRNA release. Extraordinarily, ternary Ch-SS-F-SS-PBA micelles exhibited the strongest siRNA transfection efficiencies in in vitro cell experiments and in vivo animal experiments due to the coordination of enhanced serum stability, promoted cell uptake and endosomal escape, and cell targeting ability. This strategy of constructed multifunctional polymer here we called “building-block crosslinking” showed a simple and smart way to synthesize new materials. Also this strategy of constructing ligands-directed reduction-sensitive micelles improves the transfection efficiency of LMW PEI and provides a valuable insight to develop novel gene delivery systems.
研究领域:
生物材料
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纳米技术
·
药学
·
分子生物学
✓ 已验证
DOI
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 8
·2274-2282
·
IF 6.183
Yue Cai,Zhuomin Xu,Qi Shuai,Fangtao Zhu,Jiao Xu,Xin Gao,Xuanrong Sun
Because of their excellent capacity to significantly improve the bioavailability and solubility of chemotherapy drugs, block copolymer micelles are widely utilized for chemotherapy drug delivery. In order to further improve the anti-tumor ability and reduce unwanted side effects of drugs, tumor-targeting peptides were used to functionalize the surface of polymer micelles so that the micelles can target tumor tissues. Herein, we synthesized a kind of PEG-PLA that is maleimide-terminated and then conjugated with a specific peptide F3 which revealed specific capacity binding to nucleolin that is overexpressed on the surface of many tumor cells. Then, F3 conjugated, paclitaxel loaded nanoparticles (F3-NP-PTX) were prepared as stable micelles that displayed an enhanced accumulation via a peptide-mediated cellular association in human breast cancer cells (MCF-7). Furthermore, F3-NP-PTX showed a prominent anti-tumor efficacy compared with non-targeting nanoparticles (NP-PTX) both in vitro and in vivo, and showed great potential as an efficacious targeting drug delivery system for breast cancer treatment.
研究领域:
药学
·
纳米技术
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2020
·Vol. 21
·期 5
·1856
·
IF 4.556
Qi Shuai,Yue Cai,Guangkuo Zhao,Xuanrong Sun
On account of their excellent capacity to significantly improve the bioavailability and solubility of chemotherapy drugs, amphiphilic block copolymer-based micelles have been widely utilized for chemotherapy drug delivery. In order to further improve the antitumor ability and to also reduce undesired side effects of drugs, cell-penetrating peptides have been used to functionalize the surface of polymer micelles endowed with the ability to target tumor tissues. Herein, we first synthesized functional polyethylene glycol-polylactic acid (PEG-PLA) tethered with maleimide at the PEG section of the block polymer, which was further conjugated with a specific peptide, the transactivating transcriptional activator (TAT), with an approved capacity of aiding translocation across the plasma membrane. Then, TAT-conjugated, paclitaxel-loaded nanoparticles were self-assembled into stable nanoparticles with a favorable size of 20 nm, and displayed a significantly increased cytotoxicity, due to their enhanced accumulation via peptide-mediated cellular association in human breast cancer cells (MCF-7)in vitro. But when further usedin vivo, TAT-NP-PTX showed an acceleration of the drug’s plasma clearance rate compared with NP-PTX, and therefore weakened its antitumor activities in the mice model, because of its positive charge, its elimination by the endoplasmic reticulum system more quickly, and its targeting effect on normal cells leading towards being more toxic. So further modification of TAT-NP-PTX to shield TAT peptide’s positive charges may be a hot topic to overcome the present dilemma.Keywords:cell-penetrating peptide;nanoparticles;active tumor targeting;PEG-PLA
研究领域:
药学
·
纳米技术
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癌症研究
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药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Nanomedicine
·
2020
·
IF 4.3
Dong Shen,Yan Shen,Qian Chen,Bin Huang,Yedong Mi,Yibo Shan,Guiping Yu,Thomas J Webster
Aim: Micelles are one of the most promising nanoplatforms for drug delivery, and here, cholesterol-conjugated polyoxyethylene sorbitol oleate (CPSO) micelles have been fabricated for the pulmonary delivery of paclitaxel (PTX). Materials & methods: PTX-CPSO micelles were prepared by a dialysis-ultrasonic method, and a single-factor experiment with a Box–Behnken design was conducted to optimize the formulation. Furthermore, intracellular and phagocytosis escape studies of the optimized formulation were performed on A549 and NR8383 cells. Results: The optimal micelles exhibited satisfactory encapsulation efficiency (78.48 ± 2.36%) and drug loading (17.06 ± 1.71%). In vitro studies showed enhanced CPSO micelle A549 cellular uptake and their ability to escape macrophages. Conclusion: PTX-CPSO micelles could be a promising system for pulmonary targeting by intravenous administration. Graphical abstract:
研究领域:
药学
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纳米技术
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药物递送系统
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肺医学
✓ 已验证
DOI
PubMed
高影响因子
POLYMER INTERNATIONAL
·
2024
·
IF 2.9
Xiran Shen,Tiantian Wei,Di Liu,Kang Yang,Yangang Jiang,Jianwei Lu,Li Guo
Amphiphilic block copolymers are characterized by the presence of distinct hydrophilic and hydrophobic regions, which are usually arranged in alternating blocks. This unique structure allows these copolymers to self-assemble into well-defined nanostructures that exhibit remarkable resistance to enzymatic hydrolysis, high biocompatibility and the ability to be customized with specific structures. These properties make them highly desirable in various applications. Self-assembled amphiphilic polypeptoids are currently under development as a promising class of pharmaceutical agents. However, the utilization of these peptides as drug carriers for efficient delivery presents a number of challenges. These challenges include less-than-optimal loading efficacy and restricted biocompatibility. Herein, a series of stable amphiphilic block copolypeptoids (PNEG-b-PNBG and PNEG-b-PNHG) were designed and synthesized by controlled ring-opening polymerization. PNEG chain segments provide hydrophilicity, while PNBG and PNHG chain segments provide hydrophobicity. The hydrophobic molecular chains aggregate in aqueous solutions, resulting in the formation of nano-assemblies. The self-assembled amphiphilic block polypeptoid copolymers were investigated. The morphologies of copolymers take the form of micelles from tens of nanometers to a few hundred nanometers. The properties of amphiphilic block copolypeptoids used as drug carriers were further investigated by conducting drug release and cytotoxicity tests. The results indicate that the cumulative release efficiency of self-assembled polypeptoid copolymers can reach up to about 91%. And they have good biocompatibility and can be expected to be safe materials for efficient drug delivery. This work could provide a facile method for the preparation of amphiphilic block peptoid copolymers for biopharmaceutical applications. © 2024 Society of Industrial Chemistry.
研究领域:
材料科学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
PNAS Nexus
·
2024
·Vol. 3
·期 12
·
IF 2.2
Ma Zhongjie,Jiang Miao,Song Yaohao,Sun Aile,Yi Shengzhu,Zhou Chao,Huang Xiang,Huang Mingjun,Aya Satoshi,Wei Qi-Huo
Ferroelectric nematic (NF) liquid crystals present a compelling platform for exploring topological defects in polar fields, while their structural properties can be significantly altered by ionic doping. In this study, we demonstrate that doping the ferroelectric nematic material RM734 with cationic polymers enables the formation of polymeric micelles that connect pairs of half-integer topological defects. Polarizing optical microscopy reveals that these string defects exhibit butterfly textures, featured with a 2D polarization field divided by Néel-type kink walls into domains exhibiting either uniform polarization or negative splay and bend deformations. Through analysis of electrophoretic motion and direct measurements of polarization divergences, we show that the string micelles are positively charged, and their side regions exhibit positive bound charges. To elucidate these observations, we propose a charge double-layer model for the string defects: the positively charged cationic polymer chains and densely packed RM734 molecules form a Stern charge layer, while small anionic ions and positive bound charges constitute the charge diffusion layer. Notably, our experiments indicate that only cationic polymer doping effectively induces the formation of these unique string defects. These findings enhance our understanding of ionic doping effects and provide valuable insights for engineering polar topologies in liquid crystal systems.
研究领域:
材料科学
·
物理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2024
·
IF 3.6
Mao-Lan Zhang,Gui-Ping Zhang,Hong-Shuo Ma,Yu-Zhu Pan,Xiao-Ling Liao
Considering the differences in pH between bacterial infection microenvironment and normal tissues, a series of pH-responsive drug-release amphiphilic polyurethane copolymers (DPU-g-PEG) have been prepared in this work. Fourier transform infrared (FT-IR) spectroscopy and 1H NMR was selected to detect the structure of the condensed polymers. The DPU-g-PEG amphiphilic copolymers could form stable micelles with a hydrophilic shell of polyethylene glycol (PEG) and a hydrophobic core of polylactic acid (PLA). We loaded a model drug called triclosan onto DPU-g-PEG micelles and studied how pH affects their particle size, Zeta potential, and drug release performance. The results revealed that when exposed to acidic conditions, the surface potential of DPU-g-PEG micelles changed, the micelles’ particle size increased, and the drug release performance was significantly enhanced. These results suggested that the micelles prepared in this study can release more antibacterial substances at sites of bacterial infection. Meanwhile, we also investigated the impact of different ratios of soft and hard segments on the properties of micelles, and the results showed that the pH responsiveness of micelles was strongest when the ratio of soft segments (PLLA diol + PEG 2000): 1,6-hexamethylene diisocyanate (HDI): 2,6-Bis-(2-hydroxy-ethyl)-pyrrolo[3,4-f]isoindole-1,3,5,7-tetraone (DMA) = 1: 1.2: 0.2. Furthermore, the results of inhibition zone test, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) all confirmed the antibacterial activity of triclosan-load DPU-g-PEG micelles. In conclusion, the DPU-g-PEG micelles produced in this study have the potential to be used as intelligent drug delivery systems in the biomedical field.
研究领域:
生物材料学
·
药剂学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LANGMUIR
·
2026
·
IF 4.4
Mingze Xu,Yanwei Yang,Gai Liu,Chunyun Wang,Xu Xu,Bohan Ye,Lei Liu,Xiaoyu Wu,Shiyong Song
Pluronic F127 is widely used in micelle formulations, yet its application is limited by its poor stability and low drug loading capacity. Structural modification of F127 is therefore necessary to overcome these drawbacks. Carrier materials with intrinsic pharmacological activity can reduce metabolism-related toxicity and exert synergistic effects with loaded drugs, offering broad application prospects. Solanesol (SOL), a long-chain unsaturated polyisoprenoid, exhibits antitumor activity and favorable lipophilicity. In this study, a solanesol derivative, monosolanesyl succinate (MSS), was synthesized and conjugated via an amide bond to Pluronic F127 as a hydrophobic segment, forming a pH-sensitive therapeutic nanocarrier. The critical micelle concentration (CMC) of F127-MSS was 10-fold lower than that of F127, indicating a significantly improved stability. The resulting doxorubicin-loaded F127-MSS micelles (F127-MSS-DOX) had an average particle size of approximately 130 nm and a drug loading capacity of ∼ 6.2%, which was about 4 times higher than those of F127-DOX micelles. The F127-MSS-DOX micelles exhibited pH-responsive drug release, promoting drug accumulation at tumor sites while reducing the toxicity in normal tissues. They also demonstrated excellent dilution, plasma, and storage stability. Blank F127-MSS micelles showed inherent inhibitory effects on HepG-2 and MCF-7 cells, attributed to the pharmacological activity of MSS. Furthermore, F127-MSS-DOX micelles displayed potent antitumor activity, comparable to that of free DOX at high concentrations. In vivo studies confirmed that blank F127-MSS micelles moderately suppressed tumor growth, while F127-MSS-DOX micelles significantly inhibited tumor progression and markedly reduced the systemic toxicity of free DOX, owing to their high drug loading, superior stability, pH sensitivity, and synergistic antitumor effect. These findings highlight the great potential of F127-MSS-DOX micelles for tumor treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD HYDROCOLLOIDS
·
2026
·
IF 13.8
Lingyu Han,Mengsi Nong,Jixin Yang,Jijuan Cao,Bing Hu,Peter A. Williams
Micelles are nanostructures capable of encapsulating hydrophobic substances within their hydrophobic cores, enabling their dispersion in aqueous media. This enhances the solubility, stability, and bioavailability of encapsulated bioactive compounds and allows for their controlled release. In this study, maltodextrin chains were chemically modified by adding hydrophobic octyl groups onto their backbone through an esterification reaction. As the degree of substitution increased, both the particle size of the micellar-like aggregates and the critical aggregation concentration (CAC) gradually decreased. The encapsulation efficiency and loading capacity exhibited a positive correlation with the degree of substitution. Furthermore, ultrasonic treatment, by inducing a cavitation effect, was found to enhance hydrophobic interactions within the micelles and significantly improve the encapsulation capacity and compensate for the lower degree of substitution. It also improved composite properties and imparted environmental stability to the micelle-like aggregates. In vitro modeling of the digestive process demonstrated that fucoxanthin-loaded micelle-like aggregates can effectively avoid gastric release while showing significantly enhanced intestinal release. As expected, the octyl-modified maltodextrin (MD-C8) markedly improved the bioaccessibility of fucoxanthin (49.57%) and increased the micellization rate (90.96%) during simulated gastrointestinal digestion. These findings indicate that MD-C8 is an effective delivery carrier for functional biomolecules. Combined with the approach of ultrasound-assisted techniques, it shows great potential for the applications in the encapsulation of hydrophobic compounds.
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2017
·
IF 4.3
Yuling Liu,Sai Fu,Longfei Lin,Yuhong Cao,Xi Xie,Hua Yu,Meiwan Chen,Hui Li
Pluronic F127 (F127), an amphiphilic triblock copolymer, has been shown to have significant potential for drug delivery, as it is able to incorporate hydrophobic drugs and self-assemble into nanosize micelles. However, it suffers from dissociation upon dilution owing to the relatively high critical micelle concentration and lack of stimuli-responsive behavior. Here, we synthesized the α-tocopherol (TOC) modified F127 polymer (F127-SS-TOC) via a redox-sensitive disulfide bond between F127 and TOC, which formed stable micelles at relatively low critical micelle concentration and was sensitive to the intracellular redox environment. The particle size and zeta potential of the F127-SS-TOC micelles were 51.87±6.39 nm and -8.43±2.27 mV, respectively, and little changes in both particle size and zeta potential were observed within 7 days at room temperature. With 10 mM dithiothreitol stimulation, the F127-SS-TOC micelles rapidly dissociated followed by a significant change in size, which demonstrated a high reduction sensitivity of the micelles. In addition, the micelles showed a high hemocompatibility even at a high micelle concentration (1,000 μg/mL). Low cytotoxicity of the F127-SS-TOC micelles at concentrations ranging from 12.5 μg/mL to 200 μg/mL was also found on both Bel 7402 and L02 cells. Overall, our results demonstrated F127-SS-TOC micelles as a stable and safe aqueous formulation with a considerable potential for drug delivery.
研究领域:
药剂学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Qin-Qin Gao,Chuan-Min Zhang,En-Xia Zhang,Hui-Ying Chen,Yu-Hong Zhen,Shu-Biao Zhang,Shu-Fen Zhang
As zwitterionic polymers show great promise in drug delivery, hyaluronic acid (HA) was deacetylated and grafted with dodecylamine to prepare a pH-sensitive zwitterionic polymer dHAD used as a carrier for antitumor drugs. The polymer was negatively charged at pH 7.4 and became positive at pH 6.2. In vitro delivery of DOX against MCF-7 cells showed that the blank micelle dHAD had low cytotoxicity and the dHAD-DOX micelles could greatly prohibit the growth of the MCF-7 cells. In addition, the dHAD-DOX micelles had higher cellular uptake, indicating that the micelles were rapidly internalized into the cells via CD44 receptor-mediated endocytosis. The in vivo delivery of DOX to tumor-bearing mice confirmed that the dHAD-DOX micelles greatly inhibited the tumor growth and significantly reduced systemic toxicity of DOX. These results demonstrated that biocompatible pH-responsive zwitterionic dHAD micelles are promising carriers for the delivery of DOX.
研究领域:
药剂学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Yaning Ou,Yudong Wang,Kanglin Chen,Wenxin Liao,Zhaomin Tang
We have developed a novel triple-responsive (pH/reduction/near-infrared (NIR) light) cross-linked polymer micelle PEG-P(LL/LL-LA)-PCL-IR820 for enhanced synergistic cancer therapy. This micelle was synthesized using a triblock amphiphilic polymer based on polylysine, functionalized with maleic anhydride (LA) as a cross-linking site and polycaprolactone (PCL) for encapsulating the anticancer drug doxorubicin (DOX). The photosensitizer IR820 was grafted onto PCL to enable photothermal and photodynamic effects under NIR irradiation. The DOX-loaded cross-linked micelles (DCMs) demonstrated exceptional stability under physiological conditions, effectively preventing premature drug release. Rapid DOX release was triggered by the intracellular high glutathione (GSH) level and acidic pH in tumor cells. Under NIR irradiation, DCM micelles exhibited significant photothermal and photodynamic effects, which markedly enhanced the cytotoxicity against B16 tumor cells. In B16 tumor-bearing mice, the DCM-treated group achieved superior tumor growth inhibition and prolonged survival under NIR irradiation compared to un-cross-linked micelles (DUCM) or free DOX, with minimal systemic toxicity. The tumor volume in the DCM + NIR group was significantly inhibited compared with other groups, reaching only about 300 mm3 within 15 days, while for the PBS-treated group, it reached approximately 1400 mm3. The survival rate of the DCM + NIR group was also significantly higher, with an over 70% survival rate within a 40-day observation period. This work presents a robust nanoplatform that combines stability, microenvironment responsiveness, and multimodal therapy, offering a promising strategy for targeted cancer treatment.
研究领域:
肿瘤学
·
纳米医学
·
药物递送
·
生物材料
·
转化医学
·
分子影像
✓ 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）