JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Shaojin Lu,Shiyu Zhou,Xiujuan Xiang,Biyou Zhang,Zhengyuan Xu,Qing Pei,Zhigang Xie
Improving drug delivery efficacy is the key point for enhancing the therapeutic index of medicines. Herein, we report fatty chain conjugated paclitaxel (PTX) prodrugs with a disulfide bond as linker. The formed prodrugs can self-assemble into stable nanoparticles in aqueous solutions, and rapidly transform into long-circulating nanocomplexes via the non-covalent binding to serum albumin in blood, enabling efficient drug delivery and robust antitumor effect. PTX prodrug (PC) with single-chain possess the improved self-assembly and interaction with albumins. The formed PC@albumin nanocomplexes reinforce the responsiveness of prodrug activation, and exhibit the enhanced tumor suppression ability. This strategy of hitchhiking albumin to deliver therapeutic agents holds great promise for enhanced chemotherapy.
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
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2024
·
IF 5.3
Jiahong Huang,De Bai,Lin Xie,Tianqi Liu,Jichuan Zhang,Zhenye Zhu,Chengyu Wu,Jiaheng Zhang
Although paclitaxel (PTX) is a broad-spectrum anticancer drug, its low water solubility, poor bioavailability, and susceptibility to drug resistance have seriously limited its application. In recent years, studies have shown that metformin has potential anti-tumor activity. This paper reports the successful loading of PTX into metformin oleate ionic liquid ([Met][Ole] IL) micelles and [Met][Ole] IL/tween 80 (T-80) micelles. The obtained PTX-IL/T-80 micelle exhibited a good particle size (5.77 nm) and stability (Zeta potential: −51.65 ± 7.73 mV) in addition to possessing in vitro and in vivo antitumor efficacy. The inhibition rate of PTX-IL/T-80 (10 ppm) on 4 T1 cells reached 93 %. Furthermore, the results of the in vivo treatment in mice revealed that the tumor inhibition rate of PTX-IL/T-80 under a small-dose treatment (0.5 mg·kg −1 ) was 37.7 %, which was much higher than that of the PTX prodrug group (11.7 %). Consequently, PTX-IL/T-80 has a great potential for its application in cancer therapy owing to the good synergistic antitumor effect between ([Met][Ole] ionic liquid and PTX.
研究领域:
药剂学
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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
高影响因子
BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Qianqian Qi,Zhanyu Zhang,Dun Wang
The lack of targeting and poor solubility of anti-tumor drugs are two major limitations to the outcome of tumor therapy. To address the inherent drawbacks, we designed a novel prodrug of paclitaxel (PTX), HP-PTX. This HP-PTX prodrug contains a PEGylated heptamethylene cyanine dye (PEG-IR808–1) that was conjugated to PTX via a redox-sensitive disulfide bond. The moiety of IR808–1 acts as a tumor-targeting ligand, enabling HP-PTX not only to target tumor cells, but also to localize to mitochondria and generate ROS under 808 nm laser irradiation to wound cellular mitochondria thus exerting cytotoxic effect. Meanwhile, in vitro cellular uptake assays showed that HP-PTX possesses MCF-7 cell tumor targeting specificity which was attributed to the preferential uptake of heptamethine cyanine dye mediated by the overexpressed organic anion-transporting polypeptides (OATP) on MCF-7 cell membrane. Near-infrared in vivo imaging showed that incorporation of polyethylene glycol effectively prolonged prodrug's half-life in vivo. In addition, in vivo experiments showed that with combinational therapy strategy HP-PTX was able to kill cancer cells with high efficiency (69.52 %) without notable toxic side effects compared to PTX. These results are evidence of the potential of the tumor-targeting prodrug HP-PTX for the treatment of breast cancer.
研究领域:
肿瘤学
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药理学
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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
RSC Advances
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2016
·Vol. 6
·期 36
·30184-30193
·
IF 3.289
Yu Liu,Han Zhong,Yu Qin,Yan Zhang,Xinfeng Liu,Tao Zhang
Graphene oxide (GO) and reduced graphene oxide (RGO) are attractive materials due to their potential biomedical applications, especially as drug delivery vehicles because of their huge specific surface area. In the current study, GO and RGO were prepared. In addition, a perylene derivative, phosphorylcholine oligomer grafted perylene (Perylene-PCn), was synthesized following the atom transfer radical polymerization procedure. In order to determine their structures, the products were characterized carefully with Fourier transform infrared spectra, proton nuclear magnetic resonance, X-ray photoelectron spectroscopy, wide angle X-ray diffraction, thermogravimetric analysis, and atomic force microscopy etc. The properties including fluorescence and biocompatibility were also evaluated. Utilizing the π–π stacking interaction of RGO and the perylene moiety, water dispersible RGO/Perylene-PCn composites were fabricated and then investigated as a vehicle for anti-tumor paclitaxel (PTX). The anti-tumor effects of free PTX and PTX@RGO/Perylene-PCn were compared with an in vitro cytotoxicity assay. The results demonstrated that RGO/Perylene-PCn can be used as an anti-tumor agent delivery vehicle for potential oncology applications.
研究领域:
材料科学
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生物医药工程
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肿瘤学
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DOI
高影响因子
LIFE SCIENCES
·
2019
·
IF 3.448
Like Ning,Chaoqun You,Yu Zhang,Xun Li,Fei Wang
Hydrogel for various applications, such as cell encapsulation and controlled release of drugs, has attracted the field of biomaterials in the past decades. Specially, research on the surface-modified nanocellulose hydrogel has grown rapidly on account of the importance of target delivery in the anti-cancer therapy. In this work, surface-modified nanocellulose was mixed with hexadecyl amine as long chains to blend to build a network to produce hydrogel, which was successfully developed for controlled and targeted delivery of paclitaxel. The pH-stimuli surface-modified nanocellulose hydrogel was characterized and biological evaluated in vitro. The hydrogel was stable at pH 7.4 and paclitaxel was released by the shape change of hydrogel in an acidic environment (pH 5.5), and the sustained release of paclitaxel was observed at pH 5.5. The vitro cytotoxicity studies indicated that the drug accumulation and the inhibition of A549 and HepG2 cells was effectively increased by the surface-modified nanocellulose hydrogel as compared with free paclitaxel. The inhibitory effect of A549 cells was improved by nearly 30% as compared with free paclitaxel and the apoptosis rate was up to 90.5% after 12 h incubation. In addition, the inversion test and the results of a series of cell experiments in vitro demonstrated a good performance of the surface-modified nanocellulose hydrogel.
研究领域:
生物材料
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药剂学
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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
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2012
·
IF 2.823
Yanzhu Guo,Xiaohui Wang,Xuancai Shu,Zuguang Shen,Run-Cang Sun
A series of amiphiphilic cellulose-based graft copolymers (MCC-g-PLA) with various molecular factors were synthesized in ionic liquid BmimCl and characterized by FT-IR, 1H NMR, 13C NMR, XRD, and TGA. Their solubility in a variety of solvents was compared. The prepared MCC-g-PLA copolymers can self-assemble into spherical nanomicelles (10–50 nm) in aqueous solution. The self-assembly behaviors of the MCC-g-PLA copolymers were systematically investigated by fluorescence probe. Furthermore, the hydrophobic antitumor drug paclitaxel (PTX) was successfully encapsulated into the MCC-g-PLA micelles. The drug encapsulation efficiency and loading content were found to be as high as 89.30% (w/w) and 4.97%, respectively. Results in this study not only suggest a promising cellulose-based antitumor drug carrier but also provide information for property-directed synthesis of the cellulose graft PLA copolymers.
研究领域:
药学
·
材料科学
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纳米技术
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高分子化学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2018
·
IF 3.862
Lijun Hu,Min Li,Zhipeng Zhang,Yuanyuan Shen,Shengrong Guo
Paclitaxel (PTX), one of the most potent anticancer agents , has showed a remarkable activity against varieties of tumors. However, the bioavailability of PTX is quite low due to its poor aqueous solubility. Moreover, the emerging multidrug resistance (MDR) in cancer to PTX remains a major obstacle for successful chemotherapy. In order to address these problems, we developed self-assembly of biotinylated poly(ethylene glycol)-poly(curcumin) (Biotin-PEG-PCDA) for PTX delivery (termed as PTX-BPC NPs) with the application of mPEG 2K -P(CL-co-LLA) as an emulsifier . The loading content and encapsulation efficiency of PTX were 13.2% and 92.0%, respectively. In vitro drug release study showed that PTX-BPC NPs could degrade rapidly and then release the PTX payload in a 10 mM glutathione (GSH) environment. Compared with free PTX, PTX-BPC NPs exhibited enhanced anticancer efficacy (IC 50(MCF-7/ADR cells) , 17.28 µg/mL vs. 1.15 µg/mL). In addition, these biotin-modified nanoparticles could also significantly reverse PTX resistance by suppressing the over-expression of P-gp, thus resulting in increased intracellular drug accumulation and reduced drug efflux in MCF-7/ADR cells, which showed a great anticancer effect.
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
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Jianlin Long,Yuping Yang,Tianyi Kang,Wei Zhao,Hao Cheng,Yujiao Wu,Ting Du,Beibei Liu,Yang Li,Feng Luo,Maling Gou
Nanoparticles have great promise for gene delivery. However, the transfection efficiency of nanoparticle-based gene delivery systems is always unsatisfied to meet the requirement of effective gene therapy. Herein, we used low-dosage paclitaxel to enhance a nanoscaled gene delivery system that was self-assembled from N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammoniummethyl sulfate and monomethoxy poly(ethylene glycol)–poly(d,l-lactide) (DPP), creating a paclitaxel-encapsulated DPP (P-DPP) nanoparticle. The encapsulated low-dosage paclitaxel significantly improved the gene delivery efficiency of the DPP nanoparticles against multiple cancer cells, in some of which the transfection efficiency is as high as 92%. By the P-DPP nanoparticle, vesicular stomatitis virus matrix protein (VSVMP) that could induce cell apoptosis was delivered to treat ovarian cancer. The encapsulation of paclitaxel in DPP nanoparticles increased the expression of VSVMP, enhancing VSVMP to induce antiproliferation and apoptosis in SKOV3 ovarian cancer cells. Intraperitoneal administration of P-DPP-delivered VSVMP effectively inhibited the intraperitoneal metastasis of SKOV3 ovarian cancer, which was more efficient than DPP-delivered VSVMP. Moreover, it was found that the tumor cell apoptosis induction, tumor cell proliferation inhibition, and tumor angiogenesis suppression were involved in the anticancer mechanism of this nanocomplex. Our data suggest that the encapsulation of low-dosage paclitaxel can enhance the gene delivery efficiency of the DPP nanoparticles against multiple cancer cells and exert a synergistic anticancer effect with VSVMP gene in ovarian cancer treatment. The VSVMP gene therapy delivered by the paclitaxel-enhanced nanoparticle has potential application in ovarian cancer therapy.
研究领域:
肿瘤学
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药学
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生物技术
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Mingming Song,Shuqi Dong,Xiaofei An,Wenxiang Zhang,Ning Shen,Yanbo Li,Caixia Guo,Chang Liu,Xiao Li,Siyu Chen
Chemotherapy is a difficult treatment for cancer patients because of the low effective accumulation of chemo-drugs and their detrimental side effects. Nanoparticles have shown promise as a solution to these problems. However, the known differences in the porosity and vascularization of tumor vessels, and other factors, including the potential formation of a “protein crown,” the short half-life time in circulation, and the low drug distribution, often limit their application. To address these problems, biomimetic nanoparticles coated with cell membranes have been developed and shown to have advantages such as prolonged circulation, high biocompatibility, and enhanced targeting abilities in drugs and nanoparticles, thus exhibiting good application prospects in cancer therapy for liver, lung, and melanoma cancers. Accordingly, we designed a PH-sensitive biomimetic nanodrug delivery system with a delicate “core–shell” structure based on red blood cell membranes. Briefly, core nanoparticles were synthesized by the self-assembly of natural amphoteric polymers, including hydrophilic carboxymethylcellulose sodium and hydrophobic stearic acid . For the shell structure, red blood cell membranes were modified using folic acid by a lipid tether (1,2-distearoyl-sn-glycero-3-phosphoethanolamine) to increase tumor-targeting ability, whereas polyethylene glycol was inserted to decrease lipid tether modification-induced potential sequestration by either the mononuclear phagocyte system or the reticuloendothelial system. Via a series of formulation optimizations, paclitaxel was packaged into the red blood membrane-based core–shell nanoparticles with an average size of 226.9 ± 2.75 nm and a negative Zeta potential of −14.5 ± 0.3 mV. More importantly, the examinations focusing on CD47, a representative red blood cell membrane protein, revealed not only the successful establishment of the membrane shell but also the right-side-out membrane orientation on our core–shell nanoparticles. Our nanodrug delivery system showed good biocompatibility and sensitivity to acidic tumor microenvironments while effectively prolonging the circulation time of paclitaxel and further enhancing its antitumor effects on epithelial malignancies, including liver, lung, and melanoma cancers. In particular, our nanodrug delivery system significantly alleviated paclitaxel-induced renal toxicity . Taken together, our findings highlight that the red blood membrane-based core–shell nanoparticle is a promising biomimetic nanodrug delivery system for functionally delivering chemotherapeutic drugs, and it has promise in clinical applications.
研究领域:
药学
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纳米技术
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肿瘤学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2022
·
IF 6.819
Shanshan Zheng,Yue Cai,Yulu Hong,Yubei Gong,Licheng Gao,Qingyong Li,Le Li,Xuanrong Sun
After molecule targeted drug, monoclonal antibody and antibody–drug conjugates (ADCs), peptide–drug conjugates (PDCs) have become the next generation targeted anti-tumor drugs due to its properties of low molecule weight, efficient cell penetration, low immunogenicity, good pharmacokinetic and large-scale synthesis by solid phase synthesis. Herein, we present a lytic peptide PTP7-drug paclitaxel conjugate assembling nanoparticles (named PPP) that can sequentially respond to dual stimuli in the tumor microenvironment, which was designed for passive tumor-targeted delivery and on-demand release of a tumor lytic peptide (PTP-7) as well as a chemotherapeutic agent of paclitaxel (PTX). To achieve this, tumor lytic peptide PTP-7 was connected with polyethylene glycol by a peptide substrate of legumain to serve as hydrophobic segments of nanoparticles to protect the peptide from enzymatic degradation. After that, PTX was connected to the amino group of the polypeptide side chain through an acid-responsive chemical bond (2-propionic-3-methylmaleic anhydride, CDM). Therefore, the nanoparticle (PPP) collapsed when it encountered the weakly acidic tumor microenvironment where PTX molecules fell off, and further triggered the cleavage of the peptide substrate by legumain that is highly expressed in tumor stroma and tumor cell surface. Moreover, PPP presents improved stability, improved drug solubility, prolonged blood circulation and significant inhibition ability on tumor growth, which gives a reasonable strategy to accurately deliver small molecule drugs and active peptides simultaneously to tumor sites.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Applied Nanoscience
·
2022
·Vol. 12
·期 12
·3883-3899
·
IF 3.869
Farooq Muhammad Umar,Sahin Yesim Muge,Naz Muhammad Yasin,Ijaz Salman,Shukrullah Shazia,Makhlouf Mohamed M.
A paradigm transition in cancer treatment gradually moved from "one drug-one target" toward "multi-target selective drugs design", because different drugs simultaneously inhibit tumor progression differently. The underlying mechanism has encountered significant challenges, such as encapsulating chemotherapies into a nanosized particulate system, adverse side effects, and managing multidrug-resistant. To address these issues, herein we engineered the gold nanoparticles’ surfaces with cross-linked polyethylene glycol that have well-controlled morphology and further encapsulated with commonly known chemo-drugs paclitaxel and bleomycin for nanovectorization of therapeutics to the intended site and there act through the concurrent action of dual targeting mechanisms without creating undesired side effects. The structures of the nanovectorization particulate system were confirmed by various spectroscopic techniques. The efficacy of nanovectorization particulate system and non-targeted free drugs was evaluated using the human cervical adenocarcinoma cell model. Our findings indicate that this nanovectorization particulate system had synergic stimuli-responsive characteristics and unrivaled control of efficient transportation of therapeutics agents. This system meets the high demand for multiple targeting delivery and has substantial benefits across multiple fields of nanomedicine, especially in chemotherapy.
研究领域:
纳米医学
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2026
·
IF 4.9
Weiyang Lv,Zihan Wang,Chunxin Huang,Xing Li,Lianjie Bai,Xiaotong Wang,Huilin Liu,Yunna Song,Bowen Liu,Xiaomei Ning
Abstract This study aimed to investigate the therapeutic efficacy and underlying mechanisms of paclitaxel (PTX)-loaded magnetic iron oxide nanomicrobubbles (PTX@Fe3O4 NMBs) combined with ultrasound therapy in breast cancer xenograft models. The PTX@Fe3O4 NMBs were synthesised using a modified microfluidic approach and characterised for size, stability and drug loading. Female BALB/c nude mice bearing MCF-7 xenografts were randomly divided into five groups: control, free PTX (TPL), blank NMBs with ultrasound (TPL + US), targeted NMBs with ultrasound (TLUM + US) and combination therapy with ultrasound (FA-TLUM + US). Tumour growth was monitored for 21 days. Contrast-enhanced ultrasound imaging was performed to evaluate tumour perfusion. Apoptotic mechanisms were assessed through quantitative real-time polymerase chain reaction (PCR) and Western blotting. The PTX@Fe3O4 NMBs showed a mean diameter of 186 ± 15 nm, a polydispersity index value of 0.118, a zeta potential of −21.3 ± 2.1 mV, drug encapsulation of 85.4% ± 3.2% and loading capacity of 8.6% ± 0.4% (w/w), with ≤5% drug leakage over 14 days at 4°C. The FA-TLUM + US group achieved the highest tumour growth inhibition rate of 78.6%, significantly superior to other treatment groups (p < 0.001). Contrast-enhanced ultrasound imaging demonstrated enhanced signal intensity and prolonged retention time in targeted NMB groups. Quantitative PCR analysis revealed significant upregulation of pro-apoptotic genes (Bax increased 5.0-fold, caspase-3 increased 4.2-fold) and downregulation of anti-apoptotic genes (Bcl-2 decreased by 76%, survivin decreased by 72%) in the combination therapy group. The PTX@Fe3O4 NMBs combined with ultrasound therapy demonstrated potent antitumour efficacy through enhanced drug delivery and activation of mitochondrial apoptotic pathways, representing a promising theranostic platform for breast cancer treatment.
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DOI
高影响因子
危险品化学品经营许可证（带存储）