ACS Nano
·
2025
·
IF 16
Menghua Gao,Jiafeng Zhong,Xinxin Liu,Yanjun Zhao,Dingcheng Zhu,Xiaohuo Shi,Xuehan Xu,Qin Zhou,Wenjing Xuan,Yue Zhang,Yaofeng Zhou,Jianjun Cheng
Organ- and cell-specific delivery of mRNA via modular lipid nanoparticles (LNPs) is promising in treating various diseases, but targeted cargo delivery is still very challenging. Most previous work focuses on screening ionizable and helper lipids to address the above issues. Here, we report the multifacial role of PEGylated lipids in manipulating LNP-mediated delivery of mRNA to the liver. We employed the typical excipients in LNP products, including DLin-MC3-DMA, DPSC, and cholesterol. Five types of PEGylated lipids were selected, and their molar ratio was fixed at 1.5% with a constant PEG molecular weight of 2000 Da. The architecture of steric lipids dramatically affected the in vitro gene transfection, in vivo blood clearance, liver deposition, and targeting of specific cells, all of which were closely linked to the de-PEGylation rate. The fast de-PEGylation resulted in short blood circulation and high accumulation in the liver. However, the ultrafast de-PEGylation enabled the deposition of more LNPs in Kupffer cells other than hepatocytes. Surprisingly, simply changing the terminal groups of PEGylated lipids from methoxyl to carboxyl or amine could dramatically increase the liver delivery of LNPs, which might be associated with the accelerated de-PEGylation rate and enhanced LNP–cell interaction. The current work highlights the importance of manipulating steric lipids in promoting mRNA delivery, offering an alternative approach for formulating and optimizing mRNA LNPs.
研究领域:
分子生物学
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药物递送
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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
EUROPEAN POLYMER JOURNAL
·
2019
·
IF 3.621
Chunyang Bao,Qiang Zhang
PEGylation and glycosylation are utilized in this research as different bioconjugation tools to modify proteins, yielding conjugates with different enzyme activity and assembled structure. Active succinimidyl esters are first synthesized through a facile one-step reaction for the alkyne-functionalization of proteins. Well-defined polymers with controlled MW, narrow dispersity and terminal azide groups, including thermoresponsive poly(PEG) and glycopolymers, are then synthesized via a combination of copper mediated living radical polymerization (Cu(0)-LRP) following azidation reaction. Copper catalyzed azide and alkyne cycloaddition reaction (CuAAC) is finally performed to conjugate poly(PEG) or glycopolymers with the alkyne-functionalized laccase from Trametes versicolor . The coupling of polymers induces further self-assembly of laccase-polymer conjugates into spherical nanoparticles with well dispersion stability and stimuli-responsive behaviours in water. Enzyme activity of the conjugates are also studied, during which the glycosylated laccase has shown relatively higher activity than the PEGylated laccase.
研究领域:
生物化学
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材料科学
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分子生物学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2018
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IF 3.862
Hui-Yun Zhang,Cong-yong Sun,Michael Adu-Frimpong,Jiang-nan Yu,Xi-ming Xu
The anti-tumor efficacy of curcumin can be markedly improved by nano-drug self-delivery systems with high drug loading capacity and smart stimulus-triggered drug release in tumor cells. Herein, a type of novel, glutathione (GSH)-responsive, PEGylated prodrug nano-micelles (PPNMs) was prepared by self-assembly of curcumin-s-s-vitamin E/mPEG2k-DSPE mixture. The PPNMs (entrapment efficiency: 96.7%) was acceptably stable in water with a mean particle size of 29.84 nm. Compared with curcumin-loaded mPEG2k-DSPE nano-micelles (CUR-NMs), PPNMs showed a higher drug loading (1.68% vs 27.3%) and remarkably improved the chemical stability of curcumin in phosphate buffer saline (PBS) (pH = 7.4), 10% FBS culture medium, and rat plasma. In vitro release study showed that PPNMs could redox responsively control the release of curcumin from the prodrug. Moreover, PPNMs showed a cytotoxicity in HepG2 cells similar to that of the free curcumin; however, when the HepG2 cells were pretreated with 1 mM GSH, PPNMs displayed a markedly enhanced cytotoxicity and cellular uptake than the free curcumin. After intravenous injection, PPNMs showed an increased half-life in blood circulation (10.6-fold) and bioavailability (107-fold) compared with the free curcumin injection. Altogether, the prodrug nano-micelles represent a promising preparation for sustained and controlled delivery of curcumin with enhanced antitumor activity.
研究领域:
药学
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Materials Today Nano
·
2021
·
IF 8.109
R. Sun,Q. Luo,X. Li,X. Huang,L. Teng,Z. Shen,W. Zhu
PEGylated drugs and their self-assembled nanoparticles have been used as a first-line technology in nanomedicines . However, premature disassembly before reaching the lesions under dilute conditions limits their bioavailability. This challenge can be overcome by covalent crosslinking. However, undefined molecular structures of the prodrugs are introduced, which hinder large-scale production and clinical translation. Herein, a supramolecular PEGylated camptothecin nanodrug with a crosslinked architecture and defined molecular drug structure was developed. PEGylated mono-tetraethylenepentamine β-cyclodextrin (mPEG-TEPA-CD) and adamantane modified camptothecin (AD-SS-CPT) were first synthesized. The host-guest coupling of β-cyclodextrin (β-CD) and adamantine (AD) moieties between mPEG-TEPA-CD and AD-SS-CPT induced the formation of supramolecular PEGylated camptothecin, which could self-assemble into micelles in the aqueous medium. They were further stabilized by the addition of a diacrylate crosslinker for reaction with the amine groups on mPEG-TEPA-CD, maintaining the unaltered AD-SS-CPT. The nanodrugs can internalize into tumor cells quickly and release free camptothecin in response to glutathione . They also have prolonged blood circulation time and can accumulate efficiently at tumor sites, thus showing effective antitumor activity . This supramolecular drug delivery system provides a new strategy for the design of nanodrugs.
研究领域:
药学
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纳米医学
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肿瘤学
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DOI
高影响因子
LASERS IN MEDICAL SCIENCE
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2025
·Vol. 40
·期 1
·1-11
·
IF 2.4
Ma Dan,Lu Huixiang,Zhang Hai,Liao Anru,Peng Qianrong,Yang Min
Hypoxia poses a significant challenge to the efficacy of photodynamic therapy (PDT) for cancer treatment. This study aims to design and synthesize PEGylated liposomes encapsulating MnO₂, indocyanine green (ICG), and H-chain ferritin (HFn) to potentially address hypoxia and enhance the therapeutic outcomes of PDT. PEGylated liposomes (ICG/MnO₂-HFn-mPEG-DSPE-Lip) were constructed with a rod-like structure, incorporating MnO₂ as a hypoxia-modulating agent and ICG as a photosensitizer. The drug loading capacity, stability and safety of liposomes were characterized. Singlet oxygen quantum yield (Φ Δ ) was measured under simulated tumor microenvironment conditions. In vitro phototoxicity was evaluated using A549 human lung adenocarcinoma cells. Liposomes have a high drug loading capacity, good biocompatibility and good long-term stability. Under tumor-simulated conditions, Φ Δ was significantly improved, increasing from 0.210 for free ICG to 0.507. The liposomes demonstrated remarkable phototoxic effects on A549 cells (90.5% cell death under combined PDT/PTT vs. 15% for free ICG). This nanoplatform proposes a novel strategy to overcome hypoxia-induced PDT resistance, and the enhanced efficacy may be attributed to the increased oxygen supply mediated by MnO 2 carried by HFn. These findings provide important insights for the development of next-generation therapeutic systems targeting tumor hypoxia.
研究领域:
药学
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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
Polymer Chemistry
·
2013
·Vol. 4
·期 15
·4120-4125
·
IF 5.231
Xiaoyong Zhang,Junfeng Hui,Bin Yang,Yong Yang,Daidi Fan,Meiying Liu,Lei Tao,Yen Wei
PEGylation is a popular approach for the surface functionalization of nanoparticles to achieve improved properties and better performance. Herein, we developed a facile method for surface PEGylation of hydrophobic fluoridated hydroxyapatite (FAp):Ln3+ (Ln = Eu or Tb) nanorods via hydrophobic interactions between oleic acid and amphiphilic synthetic copolymers, which were synthesized through reversible addition-fragmentation chain transfer (RAFT) polymerization using stearyl methacrylate (SMA) and poly(ethylene glycol) methacrylate (PEGMA) as monomers. Our results demonstrated that the morphology and fluorescent properties of the FAp nanorods are not significantly changed by the PEGylation procedure, and the resulting FAp nanorods were found to be stable in aqueous solution. More importantly, these PEGylated FAp nanorods are biocompatible with cells and could be utilized for cell imaging applications. Therefore, we believe that the method described in this work is a simple, efficient and general strategy for the surface PEGylation of hydrophobic nanoparticles.
研究领域:
材料科学
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生物医学工程
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DOI
高影响因子
JOURNAL OF VETERINARY MEDICAL SCIENCE
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2018
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IF 0.803
Xinrui DONG,Xueye SHU,Yingnan WANG,Zhaohuan NIU,Shixia XU,Yue ZHANG,Shuchun ZHAO
Valnemulin, successfully developed by Sandoz in 1984, is a new generation derivative of pleuromutilin related to tiamulin. Valnemulin has low water-solubility, a short half-life period, low bioavailability, and instability. The application of valnemulin was restricted. Therefore, finding a more moderate delivery system is necessary to improve the shortcomings of valnemulin. The purpose of the study was to improve the strong stability and the irritation caused by of valnemulin hydrochloride power through pegylated-valnemulin prodrug mode. The prepared pegylated-valnemulin prodrug was characterized and evaluated by in vitro release performance under buffer solutions with pH levels of 7.4 and 3.6. The loading rate of valnemulin in PEG-succinic-valnemulin prodrug was determined by ultraviolet spectrophotometer and high performance liquid chromatography (HPLC). HPLC with evaporative light scattering detector was applied to determine the amount of PEG-succinic acid. The loading rate of valnemulin in PEG-succinic-valnemulin prodrug was 6.46%. PEG-succinic-valnemulin prodrug demonstrated a satisfactory solubility of valnemulin with 523 mg·ml−1 and excellent stability verified by the stability experiment. The result of the in vitro release test showed that the prepared PEG-valnemulin prodrug has controlled release ability and the release rate of valnemulin from PEG-valnemulin prodrug with a pH of 7.4 was 64.98%, which was higher than that of pH3.6 with release rate of 31.90%. Therefore, the prepared PEG-succinic-valnemulin prodrug has great application potential.
研究领域:
药学
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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
JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
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2018
·Vol. 18
·期 8
·5542-5550
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IF 1.354
Cai Chengxu,Wang Mingzhe,Wang Liming,Wang Bing,Feng Weiyue,Chen Chunying
Characterization of bio-nano interface is crucial for developing safer and more efficient nanoparticles in nanomedical application. PEGylation is commonly used in nanocarrier for drug delivery, as it confers nanoparticles good stability, stealth effect and better targeting specificity
compared with those without PEGylation. However, the protein binding state on PEGylated AuNP is still limited known. In present work, we prepared 13 nm AuNPs and then PEGylated them with thiol PEG methoxy. Lysozyme is selected as a model protein and to investigate the interactions on protein-PEGylated/AuNP
interface. The thermal unfolding processes of lysozyme in absence and presence of PEGylated AuNP were measured by synchrotron radiation based circular dichroism (SRCD), dynamic light scattering (DLS) and infrared spectroscopy (IR). The results suggest that in terms of secondary structural
changes, α helix content is decreased, while β sheet content is increased, and thus the adsorbed lysozyme may be present in PEG layer.
研究领域:
生物化学
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纳米医学
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材料科学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Yiyang Guo,Yubin Ma,Xin Chen,Min Li,Xuehu Ma,Gang Cheng,Changying Xue,Yi Y. Zuo,Bingbing Sun
The penetration behavior of nanoparticles in mucous depends on physicochemical properties of the nanoparticles and the mucus microenvironment, due to particle–mucin interactions and the presence of the mucin mesh space filtration effect. To date, it is still unclear how the surface properties of nanoparticles influence their mucus penetration behaviors in various physiological and pathophysiological conditions. In this study, we have prepared a comprehensive library of amine-, carboxyl-, and PEG-modified silica nanoparticles (SNPs) with controlled surface ligand densities. Using multiple particle tracking, we have studied the mechanism responsible for the mucus penetration behaviors of these SNPs. It was found that PEG- and amine-modified SNPs exhibited pH-independent immobilization under iso-density conditions, while carboxyl-modified SNPs exhibited enhanced movement only in weakly alkaline mucus. Biophysical characterizations demonstrated that amine- and carboxyl-modified SNPs were trapped in mucus due to electrostatic interactions and hydrogen bonding with mucin. In contrast, high-density PEGylated surface formed a brush conformation that shields particle–mucin interactions. We have further investigated the surface property-dependent mucus penetration behavior using a murine airway distribution model. This study provides insights for designing efficient transmucosal nanocarriers for prevention and treatment of pulmonary diseases.
研究领域:
生物医学工程
·
药剂学
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产品关联
DOI
PubMed
高影响因子
CANCER LETTERS
·
2023
·
IF 9.7
Boning Niu,Yuehuang Wu,Min Zhou,Ruimiao Lin,Pengjin Ge,Xiaohui Chen,Hu Zhou,Xiaokun Zhang,Jingjing Xie
Antibody-coated nanoparticles have been reported to have the extremely low delivery efficiency in solid tumors in preclinical trials. Though aptamers were considered to be superior over antibodies in cancer theranostics, whether PEGylated aptamer nanoparticles are better than antibody nanoparticles in improving delivery specificity and penetration efficiency of chemotherapeutics is still unknown. Here, we conjugate celastrol , a natural product with anti-tumor effect, onto PEGylated EpCAM aptamer or antibody dendrimers to obtain two nanoconjugates , and for the first time, conduct a comprehensive study to compare their performance in delivery specificity, intratumoral penetration ability and therapeutic outcomes. Our results showed that compared to antibody counterparts, PEGylated aptamer nanoconjugates exhibited the enhanced accumulation and retention specificities at tumor sites and the stronger intratumoral penetration capabilities by reducing the macrophage reservoir effects in solid tumors . When delivered celastrol to a colorectal xenograft tumor mice model by PEGylated aptamer dendrimers , 20 % of enhanced therapeutic efficiency was achieved compared to that by antibody-modified ones. Moreover, celastrol at 2 mg/kg delivered by PEGylated aptamer dendrimers showed the prominent anticancer efficiency (nearly 92 %) but without obvious side effects. These data firstly provide the proof-of-concept implementation that PEGylated aptamer nanoconjugates will display the great potential in the effective and safe cancer treatment with regard to the superiority over antibody ones in penetration abilities.
研究领域:
药理学
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肿瘤学
·
纳米医学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2018
·
IF 3.862
Li Wang,Dongli Yu,Rui Dai,Duo Fu,Wenzhe Li,Zhaoming Guo,Changhao Cui,Jianqiang Xu,Song Shen,Kun Ma
Graphene oxide (GO) owns huge surface area and high drug loading capacity for aromatic molecules, such as doxorubicin (DOX). However, its biocompatibility is poor and it might agglomerate in physiological conditions. Chemical modification of GO with hydrophilic polymer, especially PEGylation , was a common method to improve its biocompatibility. But the chemical modification of GO was complicated, and its drug loading capacity might be reduced because of the occupation of its functional groups. In this study, DOX-PEG polymers with different PEG molecular weights were synthesized to modify nano graphene oxide (NGO) to simultaneously realize the solubilization of NGO and the high loading capacity of DOX. The result showed that the drug release of NGO@DOX-PEG was pH sensitive. NIR irradiation could augment the drug release, cellular uptake, cytotoxicity and nuclear translocation of nanodrugs. Among the three kinds of nanodrugs, NGO@DOX-PEG5K was superior to others. It suggested that after conjugating with PEG, the bond between DOX-PEG and NGO was weakened, which resulted in a better drug release and treatment effect. In summary, the NIR and pH dual-responsive NGO@DOX-PEG nanodrugs were developed by noncovalent modification, and it demonstrated excellent biocompatibility and photochemical therapeutic effect, presenting a promising candidate for antitumor therapy, especially NGO@DOX-PEG5K.
研究领域:
生物医学工程
·
纳米医学
·
肿瘤学
✓ 已验证
DOI
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2015
·Vol. 132
·期 40
·
IF 1.768
Xiaofen Hu,Yuyan Zhang,Huifen Zhou,Haitong Wan
PEGylated chitosans with different degrees of grafting were synthesized, and the application potential of microspheres based on PEGylated chitosan as mucoadhesive drug-delivery carriers for puerarin was investigated. Compared with chitosan microspheres, PEGylated chitosan microspheres (PCMs) exhibited better physical stability and higher swelling capacity, and the amount of water uptake increased as the content of poly(ethylene glycol) methyl ether in the microspheres increased. PCMs showed obviously improved mucoadhesive behavior on a mucosa-like surface. Puerarin was incorporated into the microspheres, and the release experiments in vitro showed that the PEGylation of chitosan accelerated puerarin release from the particles and decreased the retention of the drug. The abilities of all of the tested microspheres to open tight junctions and improve the permeability of puerarin were demonstrated with a Caco-2 cell monolayer as an in vitro model. The amount of puerarin permeating across the Caco-2 cell monolayer was significantly increased by the incorporation of puerarin into the PCMs. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132 , 42623.
研究领域:
药剂学
·
生物材料
·
药物传递系统
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）