Pharmaceutics
·
2026
·Vol. 18
·期 3
·
IF 6.9
Weilin Wang,Xin Cui,Hengfa Wei,Jingjing Wang,Yesbolat Ahehati,Cuiping Jiang,Fei Li,Shasha Li
Background/Objectives:The limited targeting efficiency and systemic toxicity of conventional medicine present significant challenges in the treatment of skeletal disorders, such as bone tuberculosis. To address these limitations, we developed a bone-targeting nanomicelle delivery system functionalized with alendronate (ALN), designated ALN-PLGA-mPEG@RPT, to improve the targeted delivery and therapeutic efficacy of rifapentine (RPT) in bone tissue.Methods:The ALN-PLGA-mPEG blank micelles, prepared in accordance with our research group’s optimized protocol, were loaded with RPT and subjected to systematic formulation optimization. The resulting nanomicellar system was comprehensively characterized in terms of its physicochemical properties, including particle size and polydispersity index (PDI). Additionally, drug-loading capacity, encapsulation efficiency, and in vitro release curve were evaluated. Bone-targeting efficacy was assessed using in vivo imaging techniques, while biodistribution and safety profiles were determined through in vivo distribution studies and histopathological examination.Results:The optimized ALN-PLGA-mPEG@RPT nanomicelles exhibited a mean particle size of 101.90 ± 4.17 nm, and a PDI of 0.242 ± 0.021. The formulation achieved a drug loading of 16.74 ± 0.51% with an encapsulation efficiency of 50.27 ± 1.91%. In vitro release studies confirmed a sustained-release profile, with only 25% of RPT released within 12 h. In vivo imaging revealed significantly enhanced bone-targeting capability in the ALN-modified group, showing a 1.93-fold higher drug accumulation in bone tissue compared to blood. Histopathological analysis indicated no observable pathological alterations in major organs.Conclusions:The ALN-PLGA-mPEG@RPT nanomicelle system exhibits favorable bone-targeting efficiency, sustained-release properties, and biocompatibility, representing a promising strategy for the precise treatment of bone tuberculosis and other skeletal diseases.
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高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 26
·4153-4160
·
IF 5.047
Qi-Bao Yan,Ning Bao,Shou-Nian Ding
The poor stability of fully inorganic halide perovskite nanocrystals (PNCs) has always restricted their wider application, especially in cell imaging. It has attracted more and more attention to use ligand engineering to improve the stability of PNCs. In this work, CsPbBr3/mPEG-NH2 NCs were synthesized using a highly biocompatible functional polymer, methoxypolyethylene glycol amine, as the capping ligand. The as-prepared CsPbBr3/mPEG-NH2 NCs exhibited superior water solubility as a result of the hydrophilic properties of mPEG-NH2. More shockingly, a significantly enhanced fluorescence intensity was found when CsPbBr3/mPEG-NH2 NCs were dispersed in water for a period of time. Correspondingly, the fluorescence quantum yield increased from the initial 16% to 41% a week later. Meanwhile, the thermal stability of the product has been greatly improved; about 80% of the initial PL intensity was still maintained after heating the product to 100 °C. Finally, we directly utilized the CsPbBr3/mPEG-NH2 NCs as luminescent probes for cell imaging for the first time.
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高影响因子
REACTIVE & FUNCTIONAL POLYMERS
·
2022
·
IF 4.966
Guoguang Chen,Qiqi Zheng,Jie Dai,Jia Liu,Jun Yin,Xiaoqing Xu,Aiping Chen,Lili Ren
Currently, the drawbacks of the chemotherapy drugs are still demonstrated poor water solubility, systemic toxicity and even multidrug resistance (MDR) in clinical applications. To address these problems, an amphiphilic block polymer self-assembled reduction sensitive micelle , mPEG-SS-PzLL/TPGS/DOX, was synthesized for efficient anticancer therapy. The polymer had a biodegradable backbone and disulfide bond can be cleaved by reduced glutathione (GHS) in tumor cells, which led to fast release of the DOX . TPGS was designed for an increaseing drug accumulation and a reduction in drug efflux. In follow-up research, we found that mPEG-SS-PzLL/TPGS/DOX micelles achieved a high encapsulation efficiency of 96.1%. Photomicrographs gotten by TEM showed homogeneous and spherical-shaped particles with the particl size of 83.7 ± 3.2 nm. The in vitro release in high reducing conditions reached 96% within 48 h. Furthermore, the mPEG-SS-PzLL/TPGS/DOX micelles caused stronger cytotoxicity to 4 T1 cells and promising therapeutic efficacy for BALB/c mice bearing 4 T1 tumors. Therefore, an excellent drug delivery system was created by combing restore sensitivity with multidrug resistance strategy while maximize drug accumulation in tumor cells. Alternatively, this study offers a bright perspective for cancer therapy with chemotherapeutics.
研究领域:
药学
·
肿瘤学
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高影响因子
International Journal of Nanomedicine
·
2026
·
IF 8.7
Zhenglu Yin,Zhaoxiang Meng,Bo Chen,Junya Wang,Aihua Zhang,Yan Shen,Xiaojia Tang,Shunyan Lin
Purpose: The clinical application of small interfering RNA (siRNA) therapy is limited by instability, inefficient tumor targeting, and inadequate responsiveness to the hypoxic tumor microenvironment. Therefore, this study aimed to construct a hypoxia-sensitive polymer-based nanocarrier to improve siRNA delivery efficiency and enhance antitumor effects in colorectal cancer (CRC).Methods: A hypoxia-sensitive polymer (mPEG-Azo-PEI) was synthesized and its cytotoxicity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The polymer was loaded with siRNA targeting the METTL3 gene to form nanoparticles, which were then optimized and characterized. Coumarin-loaded nanoparticles were also prepared to study the cellular uptake in HCT116 cells under hypoxic conditions. The Antitumor effects were evaluated via MTT and real-time polymerase chain reaction (RT-PCR) in vitro and in vivo, and a rectal cancer model was established using HCT116 cells in nude mice. Tumor size, weight, and histology (HE staining) were assessed, and RT-PCR analyzed METTL3 ex-pression.Results: The CMC of mPEG-Azo-PEI was 0.001687 mg/mL, indicating good self-assembly stability under dilution conditions. The optimized mPEG-Azo-PEI@siRNA2 nanoparticles exhibited a mean particle size of 141.34 ± 2.31 nm, a PDI of 0.213 ± 0.011, and a zeta potential of +21.76 ± 1.76 mV. Hypoxia-triggered release reached ~95% within 24 h, compared with ~10% under normoxic conditions. Coumarin uptake by HCT116 cells was enhanced under hypoxic conditions, indicating improved intracellular delivery. In vitro, the nanoparticles inhibited tumor cell proliferation, with IC50 values of 1.133 (normoxia) and 0.481 (hypoxia) nM. In vivo, mPEG-Azo-PEI@siRNA2 significantly suppressed tumor growth and improved body weight. RT-PCR confirmed the downregulation of METTL3, aligning with tumor suppression.Conclusion: These results demonstrated that hypoxia-sensitive mPEG-Azo-PEI@siRNA2 nanoparticles effectively delivered siRNA2 and inhibited HCT116 cell proliferation, offering a promising hypoxia-activated targeting strategy for colon cancer therapy. The graphical abstract illustrates the design and proposed mechanism of mPEG-Azo-PEI@siRNA nanoparticles for colorectal cancer treatment. In the upper section, mPEG-Azo-PEI is combined with siRNAs to form nanoparticles, with the particle size and surface charge indicated. In the lower section, HCT116 cells are used to establish a tumor-bearing mouse model. The magnified tumor schematic shows nanoparticles accumulating in the tumor microenvironment, where hypoxic conditions promote siRNA release from the carrier. The released siRNA is depicted as targeting METTL3 within tumor cells, illustrating the intended hypoxia-responsive gene-silencing strategy for antitumor therapy.Hypoxia-responsive mPEG-Azo-PEI nanoparticles for METTL3 siRNA delivery and antitumor therapy.
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高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2026
·
IF 5.2
Xinyi Zhang,Jingxin Gou,Yanjiao Wang,Xing Tang,Haibing He
The combination of the antiangiogenic agent nintedanib (BIBF) with the antimetabolite gemcitabine (GEM) represents a mechanistically rational yet clinically challenging strategy for breast cancer therapy. However, its clinical translation has been hindered by mismatched pharmacokinetics and the absence of a delivery system capable of coordinating their temporal release profiles. In this study, we developed a polymer-based nanoplatform designed to achieve sequential drug release: rapid initial release of BIBF to modulate the tumor microenvironment, followed by sustained release of GEM to exert cytotoxic effects. The gemcitabine prodrug (mPEG-PLG- GEM) was synthesized via covalent conjugation and subsequently used to prepare dual-loaded nanomicelles (mPEG-PLG-GEM@BIBF) through thin-film hydration. This system exhibited a well-defined sequential release profile in vitro, with BIBF released faster than the GEM prodrug. An optimal synergistic molar ratio (GEM:BIBF = 3:1) was identified. The nanomicelles (∼134.5 nm) enhanced the plasma stability and prolonged the systemic circulation of both drugs (half-lives of GEM increased from 1.38 h to 5.90 h; BIBF from 4.35 h to 8.90 h). Biodistribution studies showed increased tumor accumulation, with the intratumoral GEM:BIBF ratio maintained within the synergistic range around the target ratio of 3:1. In a 4T1 murine breast cancer model, mPEG-PLG-GEM@BIBF achieved a superior tumor inhibition rate of 77.84%, significantly outperforming the free drug combination (50.63%) and GEM monotherapy (33.54%), while also demonstrating a reduced systemic toxicity profile. This work presents a co-delivery nanoplatform designed to coordinate the release and tumor exposure of BIBF and GEM. The improved therapeutic effect is likely associated with the coordinated pharmacokinetics, enhanced tumor accumulation, and BIBF-faster-than-GEM release profile of the nanomicelles. Although direct evidence of vascular normalization and intracellular GEM activation was not obtained in this study, the results support a promising sequential co-delivery strategy for improving GEM/BIBF combination chemotherapy in breast cancer. Download: Download high-res image (206KB) Download: Download full-size image
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Polymer Chemistry
·
2012
·Vol. 3
·期 9
·2403-2412
·
IF 5.321
Lesan Yan,Wenbin Wu,Wei Zhao,Ruogu Qi,Dongmei Cui,Zhigang Xie,Yubin Huang,Ti Tong,Xiabin Jing
A functionalized six-membered cyclic carbonate monomer containing a protected thiol group, 2-(2,4-dinitrophenylthio)ethyl-5-methyl-2-oxo-1,3-dioxane-5-carboxylate (MTC), was prepared. Ring-opening polymerization (ROP) of MTC and L-lactide (LA) initiated by monohydroxyl poly(ethylene glycol) (mPEG) was successfully performed with controlled polymer molecular weight and molecular weight distribution. The structures of the obtained monomer and copolymers were confirmed by NMR and FTIR. After deprotection under mild conditions, the amphiphilic block copolymer was self-assembled into micelles in aqueous solution. By oxidation of the free thiol groups in the PMTC segments, the micelles with the cross-linked core were formed, and the enhanced stability against disruptive conditions was demonstrated by dynamic light scattering (DLS) measurement in the presence of DMF. Doxorubicin (DOX) was loaded into the micelles as a model drug. The in vitro DOX release behaviors indicated that cross-linking of the micelle cores resulted in a slow drug release and this process was greatly accelerated by adding glutathione (GSH) solution with comparable concentrations to intracellular levels in tumor cells. The cross-linked micelles were demonstrated to be efficiently internalized into the cells. Faster intracellular DOX release was observed by confocal laser scanning microscopy (CLSM) in the GSH pretreated MCF-7 cells than in the unpretreated MCF-7 cells. In vitro MTT assay revealed that the cross-linked micelles were biocompatible with L929 cells and MCF-7 cells. As expected, DOX-loaded cross-linked micelles showed higher cellular proliferation inhibition towards glutathione pretreated MCF-7 cells than that towards the unpretreated ones at various GSH concentrations. These results indicated that the bioreducible core-cross-linked micelles can be used as drug carriers for intelligent drug delivery.
研究领域:
材料科学
·
药学
·
生物医学工程
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高影响因子
Frontiers in Oncology
·
2019
·
IF 4.137
Chang Sheng,Wang Yanfei,Zhang Tianyi,Pu Xiaohui,Zong Lanlan,Zhu Heyun,Zhao Luling,Feng Bo
The toxicity and side effects of traditional chemotherapeutic drugs are the main causes of chemotherapy failure. To improve the specificity and selectivity of chemotherapeutic drugs for tumor cells, a novel redox-sensitive polymer prodrug, polyethylene glycol-poly (β-benzyl-L-aspartate) (PEG-PBLA)-SS-paclitaxel (PPSP), was designed and synthesized in this study. The PPSP micelle was manufactured via high-speed dispersion stirring and dialysis. The particle size and zeta potential of this prodrug micelle were 63.77 ± 0.91 nm and −25.8 ± 3.24 mV, respectively. The micelles were uniformly distributed and presented a spherical morphology under a transmission electron microscope. In the tumor physiological environment, the particle size of the PPSP micelles and the release rate of paclitaxel (PTX) were significantly increased compared with those of mPEG-PBLA-CC-PTX (PPCP) micelles, reflecting the excellent redox-sensitive activity of the PPSP micelles. The inhibitory effect of PPSP on HepG2, MCF-7 and HL-7702 cell proliferation was investigated with MTT assays, and the results demonstrated that PPSP is superior to PTX with respect to the inhibition of two tumor cell types at different experimental concentration. Simultaneously PPSP has lower toxicity against HL-7702 cells then PTX and PPCP. Moreover, the blank micelle from mPEG-PBLA showed no obvious toxicity to the two tumor cells at different experimental concentrations. In summary, the redox-sensitive PPSP micelle significantly improved the biosafety and the anti-tumor activity of PTX.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
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高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
Yongli Shi,Zhaomin Liu,Yaxing Yang,Xiaojie Xu,Yan Li,Tong Li
To enhance the therapeutic effects of meloxicam (MLX), we developed an oral MLX-loaded poly(ethylene glycol)-b-poly(ε-caprolactone) nanoparticles@hydrogel (MLX-NPs@hydrogel) preparation. The MLX-NPs were fabricated via a solvent evaporation method, and their morphologies were observed by a JEM-1011 transmission electron microscope (TEM). The poly(mPEGMA- co -MAA) hydrogels were synthesized, and studies on their pH sensibilities were carried out in pH 1.2, 6.8, and 7.4 buffers. The final MLX-NPs@hydrogel preparation was obtained by immersing the hydrogels in the MLX-NPs suspensions (pH 7.4) for 48 h. The thermodynamic properties and cytotoxicity of the MLX-NPs@hydrogel preparation were also studied. TEM images illustrated that mPEG-b-PCL NPs had a uniform size distribution. The poly(mPEGMA- co -MAA) hydrogels showed an excellent pH-sensibility. Thermal gravity analysis (TGA) data suggested that the protection of hydrogels improved the stability of mPEG-b-PCL NPs. The release studies revealed that MLX-NPs@hydrogel could deliver the MLX-NPs into alkalescent environment ( e.g. intestinal tract). Then, the medicated NPs released MLX at a sustained release profile. Such preparation could overcome the drawbacks of oral MLX, and enhance its therapeutic effects. Therefore, the NPs@hydrogel was a promising sustained-controlled release matrix.
研究领域:
药剂学
·
生物材料学
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高影响因子
Journal of Biomedical Nanotechnology
·
2017
·Vol. 13
·期 4
·393-408
·
IF 4.521
Tan LiWei,Ma BuYun,QianZhao .,LanZhang .,Chen LiJuan,Peng JinRong,Qian ZhiYong
In this work, docetaxel (DTX) was encapsulated in monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) micelles and monomethoxy poly(ethylene glycol)-poly(D, L-lactic acid) (mPEG-PLA) micelles, respectively. For the further application, the acute/genetic toxicity
evaluation and pharmacokinetic/pharmacodynamic study of the two kinds of micellar nanomedicines were performed. In the study of anticancer activity in vitro and in vivo, DTX micelles showed better tumorgrowth inhibition than free DTX. The pharmacokinetic and tissue distribution
studies showed that the DTX incorporated in micelles (especially in DTX-mPEG-PCL) retained significantly higher concentration in plasma and tumor tissue compared with free DTX. The acute toxicity and genotoxicity studies indicated that DTX micelles were safer than the docetaxel injection in
cancer therapy and DTX-mPEG-PCL had less damage to DNA than DTX-mPEG-PLA. So the micelles had a pronounced effect on reducing acute toxicity and genotoxicity of docetaxel. In conclusion, DTX micelles were efficient and safe on breast carcinoma chemotherapy.
研究领域:
药学
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肿瘤学
·
生物医学工程
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2018
·
IF 3.909
Yangyang Liu,Yancai Wang,Juan Zhao
This study explored the feasibility of using smart nanocaged carrier technology for the delivering of multifunctional mPEG-chitosan stabilized silybin nanocrystals and to enhancing the long-term stability, dissolution velocity and bioavailability of the water insoluble drugs. The methoxypoly(ethylene glycol)- b -poly(ε-caprolactone) (mPEG- b -PCL), as nanocaged carrier, was modified with propargyl and azide group and confirmed by FTIR . The methoxypolythylene glycol-grafted chitosan (PEG-CS), as multifunctional stabilizer, were applied for the silybin nanocrystals formulation. Two silybin nanocrystals formulations (PEG-CS nanocrystals and nanocaged nanocrystals) were prepared using anti-solvent precipitation method and optimized by central composite design-response surface model. The transmission electron microscopy , scanning electron microscopy and atomic force microscope revealed small and uniformed morphology. The crystalline state of the nanocrystals was confirmed by X-ray powder diffraction and differential scanning calorimetry . The drug structure was confirmed by Fourier transform infrared spectroscopy. During the long term stability study, the nanocaged nanocrystals were presented remarkable stability. Compared with the silybin solution, the nanocaged nanocrystals and the PEG-CS nanocrystals drug delivery system also exhibited 5.54 and 2.58 fold increasing in the AUC, respectively. Thus, the nanocaged nanocrystals technology with excellent stability, improved dissolution velocity and relative bioavailability was recommended as an efficient and feasible approach for water insoluble drugs delivery.
研究领域:
药剂学
·
纳米技术
·
药物递送系统
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高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2019
·
IF 6.361
Chuixiu Huang,Xiantao Shen,Xiaojie Liu,Zhiliang Chen,Baolian Shu,Libin Wan,Huajing Liu,Jun He
The traditional Petri dish, which has not been changed in almost 60 years, has clear limitations when it is applied to cell cultures in a modern biological laboratory. In this work, by integrating the advantages of both the semidirect breath figure (sDBF) method and the traditional breath figure (BF) method, we proposed for the first time a novel hybrid BF method for the fabrication of honeycomb-patterned Petri dishes with mPEG self-assembly in the pores. Due to the amphiphilic structure of mPEG, the active OH groups of mPEG were located inside the pores of the dishes, which could covalently couple with other functional materials . For instance, in this work, an antibacterial agent was immobilized onto the dish surface via a typical coupling reaction. Because of the size difference between the bacteria and cells, the prepared dishes had selective antibacterial activity but noncytotoxicity against mammalian cells . The present hybrid BF method provides a new insight for endowing commercial PS Petri dishes or other membranes with special topographical structures and functions, which could solve the long-term challenges of cell cultures in the future.
研究领域:
生物材料学
·
细胞生物学
·
生物医学工程
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高影响因子
RSC Advances
·
2016
·Vol. 6
·期 11
·9164-9174
·
IF 3.289
Mingjia Chen,Chunmei Gao,Shaoyu Lü,Yuanmou Chen,Mingzhu Liu
At present, diselenide bonds have been considered as a novel dual redox-sensitive linkage. Nevertheless, few studies have focused on diselenide-linked polysaccharide as new biological materials. In this work, the diselenide-linked mPEGylated starch amphiphilic copolymers (mPEG-SeSe-St), which combined the biocompatibility of polysaccharide and the stimuli-responsiveness of diselenide linkages, were developed as a novel type of PEG-detachable drug vector for rapid drug release. The amphiphilic design of the mPEG-SeSe-St enabled the formation of self-assembled micelles with spherical core–shell structures in aqueous solution. The data of well-ordered appraisals demonstrated that mPEG-SeSe-St could be disrupted in the presence of a low concentration of hydrogen peroxide (H2O2, 0.1% (v/v)) or glutathione (GSH, 1 mM). The process of diselenide bonds' more rapid degradation than disulfide bonds led to a synergistically enhanced release of loaded anticancer drugs (DOX) in cellular environments. These results, combined with cell viability measurements and confocal laser scanning microscopy (CLSM), indicated that mPEG-SeSe-St micelles might have appeared as a refined platform for cancer therapy.
研究领域:
药剂学
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生物材料科学
·
肿瘤学
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高影响因子
危险品化学品经营许可证（带存储）