查找使用阿拉丁产品的科研文献

Reduction-sensitive mixed micelles based on mPEG-SS-PzLL /TPGS to enhance anticancer efficiency of doxorubicin

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.

Fabricating a PDA-Liposome Dual-Film Coated Hollow Mesoporous Silica Nanoplatform for Chemo-Photothermal Synergistic Antitumor Therapy

Chuanyong Fan,Xiyu Wang,Yuwen Wang,Ziyue Xi,Yuxin Wang,Shuang Zhu,Miao Wang,Lu Xu

In this study, we synthesized hollow mesoporous silica nanoparticles (HMSNs) coated with polydopamine (PDA) and a D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-modified hybrid lipid membrane (denoted as HMSNs-PDA@liposome-TPGS) to load doxorubicin (DOX), which achieved the integration of chemotherapy and photothermal therapy (PTT). Dynamic light scattering (DLS), transmission electron microscopy (TEM), N2adsorption/desorption, Fourier transform infrared spectrometry (FT-IR), and small-angle X-ray scattering (SAXS) were used to show the successful fabrication of the nanocarrier. Simultaneously, in vitro drug release experiments showed the pH/NIR-laser-triggered DOX release profiles, which could enhance the synergistic therapeutic anticancer effect. Hemolysis tests, non-specific protein adsorption tests, and in vivo pharmacokinetics studies exhibited that the HMSNs-PDA@liposome-TPGS had a prolonged blood circulation time and greater hemocompatibility compared with HMSNs-PDA. Cellular uptake experiments demonstrated that HMSNs-PDA@liposome-TPGS had a high cellular uptake efficiency. In vitro and in vivo antitumor efficiency evaluations showed that the HMSNs-PDA@liposome-TPGS + NIR group had a desirable inhibitory activity on tumor growth. In conclusion, HMSNs-PDA@liposome-TPGS successfully achieved the synergistic combination of chemotherapy and photothermal therapy, and is expected to become one of the candidates for the combination of photothermal therapy and chemotherapy antitumor strategies.Keywords:chemo-photothermal therapy;hollow mesoporous silica;liposome-TPGS;polydopamine;doxorubicin

Paclitaxel-loaded ROS-responsive nanoparticles for head and neck cancer therapy

Yaqin Tu,Wei Zhang,Guorun Fan,Chenming Zou,Jie Zhang,Nan Wu,Jiahui Ding,Wen Qing Zou,Hongjun Xiao,Songwei Tan

High intracellular reactive oxygen species (ROS) level is characteristic of cancer cells and could act as a target for the efficient targeted drug delivery for cancer treatment. Consequently, biomaterials that react to excessive levels of ROS are essential for biomedical applications. In this study, a novel ROS-responsive polymer based on D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) and poly (β-thioester) (TPGS-PBTE) was synthesized for targeted delivery of the first-line antineoplastic drug, paclitaxel (PTX). The resultant TPGS-PBTE NPs showed good ROS-responsive capability in size change and drug release. Compared to PTX, PTX-loaded nanoparticles (PTX@TPGS-PBTE NPs) showed enhanced cytotoxicity and higher level of apoptosis toward squamous cell carcinoma (SCC-7) cells. Tumor-targeted delivery of the NPs was also observed, especially after being modified with a tumor-targeting peptide, cRGD. Enhanced tumor growth inhibition was also observed in head and neck cancer SCC-7 murine models. In summary, PTX@TPGS-PBTE NPs can achieve good therapeutic effects of PTX against head and neck cancer both in vitro and in vivo, especially when modified by cRGD for active targeting, which enriched the application of ROS responsive system utilized in the delivery of anticancer drugs.

Investigation of the intracellular oxidative stress amplification, safety and anti-tumor effect of a kind of novel redox-responsive micelle

Kai Dong,Chunrong Yang,Yan Yan,Pengchong Wang,Ying Sun,Ke Wang,Tingli Lu,Qiang Chen,Yanni Zhang,Jianfeng Xing,Yalin Dong

Reactive oxygen species (ROS) are one of the major intracellular metabolites. Tumor cells are usually under oxidative stress and susceptible to further ROS insults due to the excessive increase in ROS levels. Moreover, tumor cells also upregulate antioxidant systems such as glutathione (GSH) to counteract the damage caused by ROS. Therefore, the amplification of oxidative stress through increasing ROS levels to induce apoptosis could be a strategy for tumor therapy. Here we report a redox-responsive polymer micellar system, which is composed of Pluronic F127-disulfide bond-D-α-tocopheryl polyethylene glycol succinate (F127-SS-TPGS, FSST). The micelles could be degraded by the cleavage of the disulfide bond in the reductive intracellular environment, and release the ROS inducer, TPGS, which induced cytotoxicity through elevating ROS levels and inhibited mitochondrial function in tumor cells. These micelles hardly affected the function of normal cells and showed good biocompatibility. The paclitaxel-loaded FSST-PTX micelles significantly improved the cytotoxicity of PTX. In vivo experiments revealed that the FSST-PTX micelles prolonged the circulation and enhanced the treatment of PTX. In conclusion, FSST could be a potential vehicle for cancer treatment.

Nanoengineering of a newly designed chlorin e6 derivative for amplified photodynamic therapy via regulating lactate metabolism

Xiaohan Qin,Mengzhu Zhang,Xu Hu,Qian Du,Zhipeng Zhao,Yue Jiang,Yuxia Luan

Chlorin e6 (Ce6) is a widely utilized photosensitizer in photodynamic therapy (PDT) against tumor growth, but its hydrophobic feature and the hypoxia in the tumor microenvironment greatly compromise its therapeutic efficacy. To address the issues, here we designed a new Ce6 derivative (TCe6) by coupling Ce6 with amphiphilic D-α-tocopherol polyethylene glycol 1000 succinate (TPGS), endowing Ce6 with an excellent amphiphilic feature. In particular, the overall reactive oxygen species (ROS) generation by TCe6 was significantly enhanced because TPGS could interact with mitochondrial complex II to induce extra ROS production, amplifying the total ROS production under PDT. Inspired by the unique property of α-cyano-4-hydroxycinnamate (CHC) in regulating lactate metabolism to spare more intracellular oxygen for PDT, TCe6 was further co-assembled with CHC to construct TCe6/CHC nanoparticles (NPs) for addressing the insufficient oxygen issue in PDT. The as-prepared TCe6/CHC NPs not only increased the efficiency of cell internalization but also improved the solubility and stability of Ce6 and CHC. Thanks to the extra ROS production by the TPGS unit, the amphiphilic feature of TCe6 and the CHC-mediated hypoxia microenvironment, the TCe6/CHC NPs demonstrated excellent PDT against tumor growth. This work provided a versatile strategy to solve the current bottleneck in photosensitizer-based PDT, holding great promise for the design of advanced photodynamic nanoplatforms.

TPGS-b-PBAE Copolymer-Based Polyplex Nanoparticles for Gene Delivery and Transfection In Vivo and In Vitro

Jiahui Ding,Handan Zhang,Tianli Dai,Xueqin Gao,Zhongyuan Yin,Qiong Wang,Mengqi Long,Songwei Tan

Poly (β-amino ester) (PBAE) is an exceptional non-viral vector that is widely used in gene delivery, owing to its exceptional biocompatibility, easy synthesis, and cost-effectiveness. However, it carries a high surface positive charge that may cause cytotoxicity. Therefore, hydrophilic d-α-tocopherol polyethylene glycol succinate (TPGS) was copolymerised with PBAE to increase the biocompatibility and to decrease the potential cytotoxicity of the cationic polymer-DNA plasmid polyplex nanoparticles (NPs) formed through electrostatic forces between the polymer and DNA. TPGS-b-PBAE (TBP) copolymers with varying feeding molar ratios were synthesised to obtain products of different molecular weights. Their gene transfection efficiency was subsequently evaluated in HEK 293T cells using green fluorescent protein plasmid (GFP) as the model because free GFP is unable to easily pass through the cell membrane and then express as a protein. The particle size, ζ-potential, and morphology of the TBP2-GFP polyplex NPs were characterised, and plasmid incorporation was confirmed through gel retardation assays. The TBP2-GFP polyplex NPs effectively transfected multiple cells with low cytotoxicity, including HEK 293T, HeLa, Me180, SiHa, SCC-7 and C666-1 cells. We constructed aMUC2(Mucin2)-targeting CRISPR/cas9 gene editing system in HEK 293T cells, with gene disruption supported by oligodeoxynucleotide (ODN) insertion in vitro. Additionally, we developed anLMP1(latent membrane protein 1)-targeting CRISPR/cas9 gene editing system in LMP1-overexpressing SCC7 cells, which was designed to cleave fragments expressing the LMP1 protein (related to Epstein–Barr virus infection) and thus to inhibit the growth of the cells in vivo. As evidenced by in vitro and in vivo experiments, this system has great potential for gene therapy applications.Keywords:poly (β-amino ester);gene transfection;D-α-tocopherol polyethylene glycol succinate;copolymer;CRISPR/cas9 gene editing;gene therapy

Enhancement of in vitro dissolution and in vivo performance/oral absorption of FEB-poloxamer-TPGS solid dispersion

Xiaoxia Sheng,Jingjing Tang,Jiayin Bao,Xiangjun Shi,Weike Su

In the present study, a febuxostat (FEB) solid dispersion was prepared via the solvent evaporation method, and the dispersion's solubility, dissolution rate and oral bioavailability were investigated. To select the appropriate carriers for the FEB solid dispersion, series of preliminary trials were performed on d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), HPMC, PEG4000, PEG6000, Eudragital, PVA, PVP K30, poloxamer188 and poloxamer407. Based on the preliminary trials, TPGS and poloxamer188 were selected as the carriers for the FEB solid dispersion preparation. In addition, a mixture of FEB:poloxamer188:TPGS (1:5:1) exhibited outstanding characteristics; its saturation solubility was 7.31 times (in water), 17.67 times (in pH 1.2), 17.22 times (in pH 4.5), 3.60 times (in pH 6.0) and 1.99 times (in pH 6.8) higher than that of pure crystalline FEB. In an in vitro drug dissolution study, the mixture exhibited a drug release rate that was 1.94 times that of the FEB API. Meanwhile, oral bioavailability, C max and AUC, as evaluated in an in vivo pharmacokinetic study, also showed a notable enhancement.

mPEG-Cholic acid/TPGS mixed micelles for combined delivery of paclitaxel and bufalin to treat hepatocellular carcinoma

Yujia Liu,Xiaoyu Lu,Zhenhai Zhang,Shulong Jiang,Huixia Lv

In this study, amphiphilic block copolymer mPEG-cholic acid was synthesized in conjunction with TPGS as stabilizer to prepare multifunctional micelles. The formed polymeric micelles (PCTm) were used for the delivery of paclitaxel (PTX) and bufalin (BF). PEG group could enhance solubility and extend circulation time, while cholic acid groups achieved the liver targeted function. Combinations of these approaches could realize a synergistic therapeutic effect in the treatment of advanced hepatocellular carcinoma. CLSM in vitro results demonstrated that drug capsulation into PCTm could enhance cellular uptake. FCM results confirmed the uptake amount of C6/PCTm was 7.5-fold higher than that of free C6 after incubation for 2 h. Competitive inhibition test proved the Na+-taurocholate co-transporting polypeptide (NTCP) involved in the uptake mechanism of PCTm. Meanwhile, in vivo imaging assays demonstrated that the fluorescence intensity of Cy5.5/PCTm was higher than that of free Cy5.5 on liver and tumor with extended circulation time to 48 h. In addition, in vivo studies confirmed that the combined therapy exhibited the strongest tumor inhibition rate of 82.29% with lower systemic toxicity. Hence, these results indicated that PCTm could provide a promising strategy for targeting hepatocellular carcinoma and achieve the goal of synergism and attenuation.

Enhanced oral bioavailability of self-assembling curcumin–vitamin E prodrug-nanoparticles by co-nanoprecipitation with vitamin E TPGS

Huiyun Zhang,Baoding Chen,Yuan Zhu,Congyong Sun,Michael Adu-Frimpong,Wenwen Deng,Jiangnan Yu,Ximing Xu

Solubility improvement of curcumin by crystallization inhibition from polymeric surfactants in amorphous solid dispersions

Ziyue Xi,Yali Fei,Yuxin Wang,Qing Lin,Qidong Ke,Guotai Feng,Lu Xu

To improve the solubility and maintain amorphous state of curcumin (CUR), solid dispersions of CUR with Kollidon CLSF and surfactant (TPGS or HPMC) were prepared by solvent evaporated method. The solid dispersions were characterized by scanning electron microscope, powder X-ray diffraction, differential scanning calorimetry and fourier transform infrared spectroscopy . The solubilization mechanism of surfactants in vitro and the pharmaceutical properties of optimal formulations in vivo were studied. The results showed that TPGS as a carrier provided superior solubility and stability for SDs due to its stable hydrogen bonding strength and related crystal nuclei growth mechanism. At different pH conditions (pH 1.2 and 6.8), TPGS significantly improved the solubility and release rate of CUR in solid dispersions. Thus, solid dispersion with high solubility and stability significantly enhanced the oral bioavailability and gastric ulcer healing rate. Therefore, solid dispersion with novel applied surfactants is an effect strategy to improve pharmaceutical properties of CUR.

Brigatinib-repurposed chemo-photodynamic therapy nanoplatform via effective apoptosis against colorectal cancer

Miao Su,Hailong Tian,Li Zhou,Qiong Li,Shuqi Wang,Canhua Haung,Edouard C. Nice,Shaojiang Zheng,Jingquan Li

Colorectal cancer (CRC), a malignancy with a relatively high fatality rate, still poses a growing global public health challenge due to the lack of well-established and effective treatment strategies. Brigatinib, an ALK inhibitor approved for the treatment of ALK-positive NSCLC, has been repurposed to suppress the growth of ALK-negative CRC cells via sustained endoplasmic reticulum (ER) stress. Moreover, the photosensitizer Chlorine e6 (Ce6) exhibits a high singlet oxygen quantum yield, which promote the generation of reactive oxygen species (ROS) to exacerbate ER stress and function synergistically with chemotherapeutics. However, the clinical application of both brigatinib and Ce6 is limited by their poor water solubility. Therefore, a repurposed chemo-photodynamic therapy nanoplatform (BCT NPs) utilizing d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a nanocarrier for the codelivery of the chemotherapeutics brigatinib and photosensitizer Ce6 is developed, which is capable of disrupting redox homeostasis and enhancing ER stress against CRC. The developed nanoplatform successfully addressed therapeutic drug solubility, improved brigatinib biocompatibility with a lower hemolysis rate, and demonstrated satisfactory CRC suppression effects in vitro and in vivo . Overall, BCT NPs provide a promising strategy to construct repurposed and versatile nanoplatforms against CRC.

Targeted and Specific Modification with 4-Carboxybenzeneboronic Acid and TPGS of Fluorescent Gold Nanoparticles and the Enhanced Antitumor Activity Research

Qiaoqiao Zhou,Shaochen Wang,Peng Hu,Shuling Yu,Jiahua Shi,Jintao Yuan

A targeting and specific fluorescent gold nanoparticle is prepared for tracing of drug and effective treatment of cancers. First, 4-carboxybenzeneboronic acid (CBPA) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) are used to modify cyclodextrins (CDs), then modified cyclodextrins and polyethylene glycol (PEG) are used to stabilize gold nanoclusters to prepare fluorescent gold nanoparticles (AuNCs@CD-TPGS-CBPA/PEG). CBPA has targeting and TPGS can induce apoptosis, therefore, AuNCs@CD-TPGS-CBPA/PEG has targeting and certain anti-tumor activity. The structure and morphology of the nanomaterial are characterized by using nuclear magnetic resonance (NMR) spectroscopy and transmission electron microscope (TEM). Paclitaxel (PTX) is loaded into the hydrophobic cavity of CDs to form targeting specific drug-loaded fluorescent gold nanoparticles (AuNCs@CD-TPGS-CBPA/PEG/PTX). Biological performances of AuNCs@CD-TPGS-CBPA/PEG are studied by in vitro and in vivo experiments. In vitro test results confirm that AuNCs@CD-TPGS-CBPA/PEG could be internalized by tumor cells, and effectively against tumor cells, but it is biocompatible to normal cells. In vivo experiments prove that AuNCs@CD-TPGS-CBPA/PEG has excellent targeting, biocompatibility, and enhanced antitumor capability, could enrich and stay for a long time in the tumor regions, effectively prolong the lifetime of tumor-bearing mice. Therefore, this work provides an insight into the development of fluorescent gold nanomaterials for practical biomedical application.