CHEMICAL & PHARMACEUTICAL BULLETIN
·
2015
·Vol. 63
·期 2
·68-74
·
IF 1.164
Wen Lv,Lihua Cheng,Baohua Li
One of the major obstacles to successful paclitaxel (PTX) chemotherapy is toxic side effects, which are often due to the conventional surfactants used, such as Cremophor EL. PTX is characterized by its hydrophobicity and insolubility, which limit its application in ovarian cancer therapy. The aim of this study was to develop Cremophor EL-free PTX-loaded methoxy poly(ethylene glycol)-block-(lactic-co-glycolic acid) copolymers (PLGA-mPEG) nanoparticles (NPs) using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a novel emulsifier. The ability of nanoparticles loaded with paclitaxel (NP-PTX) to inhibit tumor growth was assessed in vitro and in vivo. The acute toxicity of NP-PTX was also evaluated in vivo. We found that paclitaxel was efficiently encapsulated into PLGA-mPEG NPs with a low concentration of TPGS as the emulsifier. The synthesized NP-PTX demonstrated the desired diameter of 80 nm as characterized by transmission electron microscopy. The NP-PTX also exhibited a sustained release of loaded PTX over 4 d with the same chemotherapeutic efficiency and reduced side effects. NP-PTX-treated cells showed slightly lower cytotoxic responses compared with those treated with free PTX at the same concentration. In vivo studies confirmed that NP-PTX significantly enhanced the median lethal dose of paclitaxel by 10-fold, and a similar effect on the inhibition of tumor growth was achieved in nude mice.
研究领域:
药剂学
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肿瘤学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
·
IF 6.6
Rui Gao,Peihong Lin,Wenjing Yang,Zhengyu Fang,Chunxiao Gao,Bin Cheng,Jie Fang,Wenying Yu
Background Genistein (Gen), a natural polyphenolic compound, has emerged as a promising candidate for lung cancer treatment. However, the potential clinical application of Gen is limited due to its poor solubility, low bioavailability, and toxic side effects. To address these challenges, a biomimetic delivery platform with cell membranes derived from natural cells as carrier material was constructed. This innovative approach aims to facilitate targeted drug delivery and solve the problem of biocompatibility of synthetic materials.Methods First, the liposomes (LPs) loaded with Gen (LPs@Gen) was prepared using the ethanol injection method. Subsequently, PLTM-LPs@Gen was obtained through co-extrusion after mixing platelet membrane (PLTM) and LPs@Gen. Additionally, the biological and physicochemical properties of PLTM-LPs@Gen were investigated. Finally, the targeting ability, therapeutic efficacy, and safety of PLTM-LPs@Gen for lung cancer were evaluated using both a cell model and a tumor-bearing nude mouse model.Results The optimal preparation ratio for LPs@Gen was Gen: soybean lecithin: cholesterol: DSPE-PEG2000 (3:30:5:10, mass ratio), while the ideal fusion ratio of LPs@Gen and PLTM was 1:1. The particle size of PLTM-LPs@Gen was 108.33 ± 1.06 nm, and the encapsulation efficiency and drug loading were 94.29% and 3.09% respectively. Gen was released continuously and slowly from PLTM-LPs@Gen. Moreover, PLTM-LPs@Gen exhibited good stability within one week. The results of in vitro cellular uptake and in vivo distribution experiments indicated that the carrier material, PLTM-LPs, has the immune escape ability and tumor targeting ability. Consequently, it showed better therapeutic effects than free drugs and traditional LPs in vitro and in vivo tumor models. In addition, safety experiments demonstrated that PLTM-LPs@Gen possesses good biocompatibility.Conclusion Biomimetic nanomedicine provides a new strategy for the precision treatment of lung cancer in clinical practice.
研究领域:
药学
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纳米技术
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癌症研究
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生物医学工程
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2018
·
IF 3.997
Shujuan Xiong,Zhe Wang,Juan Liu,Xiangping Deng,Runde Xiong,Xuan Cao,Zhizhong Xie,Xiaoyong Lei,Yanming Chen,Guotao Tang
This work has presented a novel strategy for designing pH-sensitive TOS-H-DOX prodrug-loaded TPGS nanomicelles for co-delivery TOS and DOX to enhance tumor therapy and reduce the toxic side effects. DOX was covalently conjugated to the vitamin E succinate through hydrazone bond to produce an pH-sensitive prodrug TOS-H-DOX (amido bond as a control, TOS-A-DOX), which was responsive to the acidic environment in tumor cells, and the prodrugs were subsequently encapsulated in the core of TPGS nanomicelles via hydrophobic effects with a significant drug loading capacity. The pH-sensitive prodrug nanomicelles TOS-H-DOX/TPGS exhibited potent release of DOX in acidic media relative to the pH-insensitive prodrug nanomicelles TOS-A-DOX/TPGS, and further studies of their intracellular uptake and intracellular localization demonstrated that TOS-H-DOX/TPGS nanomicelles can be effectively taken up by cells and drugs can be released. In vitro results confirmed that TOS-H-DOX/TPGS nanomicelles exhibited significant antitumor cell proliferation activity compared to TOS-A-DOX/TPGS and free DOX, TPGS. Furthermore, in vivo studies further confirmed an excellent synergistic antitumor efficacy in MCF-7 tumor-bearing nude mice model. More importantly, the H&E staining of the heart, liver, kidney tissue sections of experimental nude mice showed that TOS-H-DOX/TPGS nanomicelles can reduce damage to them.
研究领域:
药学
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纳米技术
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癌症治疗
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Qiankun Sun,Ju Liang,Yang Lin,Yunyun Zhang,Fuqing Yan,Wenlan Wu
Multi-vesicular vesicles (MVVs) offer structural advantages in terms of drug encapsulation and physiological stability. In this study, we address the challenge of preparing small-sized MVVs for drug delivery. The nano-sized MVVs (~120 nm) loaded with doxorubicin (DOX) and curcumin (CUR) (DOX/ [email protected] ) were successfully prepared using a glass bead combined with a thin film dispersion method. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis confirmed the independent non-homocentric vesicle structures of DOX/ [email protected] with homogeneous particle sizes. The experimental results showed high encapsulation rates of DOX and CUR in DOX/ [email protected] , reaching 82.5±0.75% and 85.9±0.69%, respectively. Moreover, the MVVs exhibited good biosafety and sustained release properties. Notably, the bioavailability of DOX and CUR in DOX/ [email protected] was enhanced compared to free DOX and CUR, with increases of 4.2 and 2.1 times, respectively. And the half-life of DOX and CUR was extended by 10 times in DOX/ [email protected] In vivo antitumor experiments demonstrated that nano-sized DOX/ [email protected] significantly improved the antitumor activity while reducing the toxic side effects of DOX. Overall, the successful preparation of nano-sized DOX/ [email protected] and their potent and low-toxic antitumor effects provide a critical experimental reference for the combined antitumor therapy of MVVs and liposomes.
研究领域:
药学
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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
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2016
·
IF 8.387
Yao Wang,Xiali Ding,Yuan Chen,Mingquan Guo,Yan Zhang,Xiaokui Guo,Hongchen Gu
Drug-resistant bacterial infections have become one of the most serious risks in public health as they make the conventional antibiotics less efficient. There is an urgent need for developing new generations of antibacterial agents in this field. In this work, a nanoplatform of LEVO-loaded and silver core-embedded mesoporous silica nanovehicles (Ag@MSNs@LEVO) is demonstrated as a synergistic antibacterial agent for the treatment of drug-resistant infections both in vitro and in vivo. The combination of the inner Ag core and the loaded antibiotic drug in mesopores endows the single-particle nanoplatform with a synergistic effect on killing the drug-resistant bacteria. The nanoplatform of Ag@MSNs@LEVO exhibits superior antibacterial activity to LEVO-loaded MSNs (MSNs@LEVO) and silver core-embedded MSNs (Ag@MSNs) in vitro. In the in vivo acute peritonitis model, the infected drug-resistant Escherichia coli GN102 in peritoneal cavity of the mice is reduced by nearly three orders of magnitude and the aberrant pathological feature of spleen and peritoneum disappears after treatment with Ag@MSNs@LEVO. Importantly, this nanopaltform renders no obvious toxic side effect to the mice during the tested time. There is no doubt that this study strongly indicates a promising potential of Ag@MSNs@LEVO as a synergistic and safety therapy tool for the clinical drug-resistant infections.
研究领域:
纳米技术
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药学
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微生物学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2023
·
IF 5
Jicheng Cui,Wenjing Zhao,Jiangtao Wu,Dongmei Zhang,Longguang Liu,Hui Qiao,Zeyu Yan,Yuejun Fu,John F. Trant,Yingqi Li
Combination chemotherapy can slow the emergence of resistance, but can also lead to a significant exacerbation of off-target effects. Mediated drug release can ameliorate this situation: in this study, mitoxantrone (MTO) and doxorubicin (DOX) were co-loaded onto a nanodiamond (ND) scaffold, through physical adsorption, to prepare an ND/MTO/DOX (NMD) nanodrug. The drug loading of MTO and DOX were 119 ± 3 μg mg −1 and 60 ± 3 μg mg −1 , respectively. This NMD exhibits excellent stability with negligible drug leakage upon storage. The NMD nanoparticles enter cells via the clathrin and caveolae co-mediated endocytosis pathways and primarily remain within the lysosomes. Cytotoxicity tests showed that the NMD has an enhanced synergistic effect compared with an ND loaded with either drug alone, and has a slow but effective rate of drug release. Intraperitoneal injection of the NMD-drug into tumor-bearing mice demonstrated that the NMD rapidly localizes to the tumor site with very limited dispersion to other organs. The NMD strongly suppressed tumor growth in vivo with significantly reduced toxic side effects compared to mice treated with the free drugs. These results suggest that the as-prepared NMD has potential clinical applications for the targeted co-delivery of multiple chemotherapeutics.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Jingtong Wang,Zhao Li,Yajing Chen,Ningbin Luo,Shengbin He
With a number of outstanding properties, gelatin is an ideal candidate for assembling nanoplatforms in biomedical applications. Generally, gelatin nanocarriers are cross-linked by aldehydes to improve their stability in water solution. However, aldehydes could cause multiple toxicities and their cross-linking products are uncontrollable. Here, we first used a self-immolative cross-linker to assemble gelatin nanocarriers for the controlled release of drugs and targeted cancer therapy. The cross-linker contains a disulphide bridge and two symmetrical succinimidyl-esters, endowing it with multiple functions: 1) to cross-link the gelatin nanocarriers and thus improve their stability in water; 2) to conjugate the drug and tumor-targeting ligands with nanocarriers through covalent linkage; 3) to redox-responsively degrade the nanocarriers through hydrolysis of disulphide bridge; and 4) to produce traceless drug molecules through self-immolative reaction. Good biocompatibility and controllable drug release were demonstrated by in vitro experiments. Both qualitative and quantitative analyses confirmed the intracellular uptake of the nanocarriers by using doxorubicin (DOX) as a drug model and phenylboronic acid (PBA) as the targeting ligand. In vivo results demonstrated high therapeutic efficiency and low toxic side effects of the DOX loaded nanocarriers against artificial liver tumors.
研究领域:
药学
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纳米技术
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癌症研究
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2022
·Vol. 20
·期 1
·1-13
·
IF 9.429
Luo Zhenyu,Luo Lihua,Lu Yichao,Zhu Chunqi,Qin Bing,Jiang Mengshi,Li Xiang,Shi Yingying,Zhang Junlei,Liu Yu,Shan Xinyu,Yin Hang,Guan Guannan,Du Yongzhong,Cheng Ningtao,You Jian
Adoptive cell therapy (ACT) was one of the most promising anti-tumor modalities that has been confirmed to be especially effective in treating hematological malignancies. However, the clinical efficacy of ACT on solid tumor was greatly hindered by the insufficient tumor-infiltration of cytotoxic CD8 + T cells. Herein, we constructed a nanoplatform termed dual-binding magnetic nanoparticles (DBMN) that comprised PEG-maleimide (Mal), hyaluronic acid (HA) and Fe3O4 for adoptive T cell-modification and ACT-sensitization. After a simple co-incubation, DBMN was anchored onto the cell membrane (Primary linking) via Michael addition reaction between the Mal and the sulfhydryl groups on the surface of T cells, generating magnetized T cells (DBMN-T). Directed by external magnetic field and in-structure Fe3O4, DBMN-T was recruited to solid tumor where HA bond with the highly expressed CD44 on tumor cells (Secondary Linking), facilitating the recognition and effector-killing of tumor cells. Bridging adoptive T cells with host tumor cells, our DBMN effectively boosted the anti-solid tumor efficacy of ACT in a mouse model and simultaneously reduced toxic side effects.
研究领域:
癌症研究
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纳米技术
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免疫疗法
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 8
·期 4
·655-665
·
IF 5.047
Zhanxia Zhang,Wei Cheng,Yongfu Pan,Lijun Jia
Stimuli response or controlled release is a new research hotspot in nanomedicine; however, there is scarce research on organic nanomedicines with stimuli responses, which limits their practical biological applications. In addition, homoharringtonine (HHT) has been used as an effective anticancer agent, but reducing its toxicity and side effects is an urgent problem to be solved. Herein, an EGFR (epidermal growth factor receptor) aptamer-modified HHT-loaded PLGA-SS-PEG nanomedicine was developed. The nanomaterial possesses spherical morphology and admirable biocompatibility. After targeted endocytosis in tumour cells via the selective recognition between EGFR and its aptamer, the PLGA nanomedicine is triggered by a high GSH level and releases its cargo in lung cancer cells. The in vitro and in vivo results reveal that the PLGA nanomedicine not only inhibited the proliferation and promoted the apoptosis of lung cancer cells, but also possessed better therapeutic efficacy and less toxic side effects compared with the free anticancer agent. Consequently, this study provides a novel approach to construct a biodegradable nanomedicine with targeted recognition and stimuli response. Moreover, it inhibited the proliferation of lung cancer cells with high efficiency and low toxicity. Importantly, the PLGA nanomedicine demonstrates encouraging potential as a multifunctional nano-system applicable for cancer therapy.
研究领域:
药学
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纳米技术
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癌症研究
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2019
·
IF 10.273
Hongxing Liu,Weiqiang Lin,Lizhen He,Tianfeng Chen
Developing safe, effective and targeting radiosensitizers with clear action mechanisms to achieve synergistic localized cancer treatment is an important strategy for radiotherapy . Herein, we design and synthesize a ternary heteronanostructure radiosensitizer (SeAuFe-EpC) with core/satellite morphology by a simple method to realize multimodal imaging-guided cancer radiotherapy. The mechanistic studies reveal that Se incorporation could drastically improve the electrical conductivity and lower the energy barrier between the three components, resulting in more electrons transfer between Se-Au interface and migration over the heterogeneous junction of Au-Fe 3 O 4 NPs interface. This synergistic interaction enhanced the energy transfer and facilitated more excited excitons generated by SeAuFe-EpC NPs, thus promoting the transformation of 3 O 2 to 1 O 2 via resonance energy transfer, finally resulting in irreversible cancer cell apoptosis. Additionally, based on the X-ray attenuation ability and high NIR absorption of AuNPs and the superparamagnetism of Fe 3 O 4 , in vivo computer tomography , photoacoustic and magnetic resonance tri-modal imaging have been employed to visualize the tracking and targeting ability of the NPs. As expected, the NPs specifically accumulated in orthotopic breast tumor area and achieved synergistic anticancer efficacy, but showed no toxic side effects on main organs. Collectively, this study sheds light on the potential roles of core/satellite heteronanostructure in imaging-guided cancer radiotherapy.
研究领域:
癌症治疗
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纳米技术
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生物医学工程
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成像科学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Xinyu Yao,Jinying Gao,Lanqiao Wang,Xiaoning Hou,Litao Ge,Xinxin Qin,Jiazhang Qiu,Xuming Deng,Wei Li,Jianfeng Wang
Ethnopharmacology relevance Cananga oil (CO) is derived from the flowers of the traditional medicinal plant, the ylang-ylang tree. As a traditional antidepressant, CO is commonly utilized in the treatment of various mental disorders including depression, anxiety, and autism. It is also recognized as an efficient antibacterial insecticide, and has been traditionally utilized to combat malaria and acute inflammatory responses resulting from bacterial infections both in vitro and in vivo . Aim of the study The objective of this study is to comprehensively investigate the anti- Salmonella activity and mechanism of CO both in vitro and in vivo , with the expectation of providing feasible strategies for exploring new antimicrobial strategies and developing novel drugs. Methods The in vitro antibacterial activity of CO was comprehensively analyzed by measuring MIC, MBC, growth curve, time-killing curve, surface motility, biofilm, and Live/dead bacterial staining. The analysis of the chemistry and active ingredients of CO was conducted using GC-MS. To examine the influence of CO on the membrane homeostasis of Salmonella , we conducted utilizing diverse techniques, including ANS, PI, NPN, ONPG, BCECF-AM, DiSC3(5), and scanning electron microscopy (SEM) analysis. In addition, the antibacterial mechanism of CO was analyzed and validated through metabolomics analysis. Finally, a mouse infection model of Salmonella typhimurium was established to evaluate the toxic side effects and therapeutic effects of CO. Results The antibacterial effect of CO is the result of the combined action of the main chemical components within its six (palmitic acid, α-linolenic acid, stearic acid, benzyl benzoate, benzyl acetate, and myristic acid). Furthermore, CO disrupts the balance of purine metabolism and the tricarboxylic acid cycle (TCA cycle) in Salmonella , interfering with redox processes. This leads to energy metabolic disorders and oxidative stress damage within the bacteria, resulting in bacterial shock, enhanced membrane damage, and ultimately bacterial death. It is worth emphasizing that CO exerts an effective protective influence on Salmonella infection in vivo within a non-toxic concentration range. Conclusion The outcomes indicate that CO displays remarkable anti- Salmonella activity both in vitro and in vivo . It triggers bacterial death by disrupting the balance of purine metabolism and the TCA cycle, interfering with the redox process, making it a promising anti- Salmonella medication.
研究领域:
药理学
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微生物学
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代谢组学
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传染病学
✓ 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）