INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2017
·
IF 3.649
Xiaofeng Han,Xuerong Dong,Jing Li,Manyuan Wang,Lei Luo,Zhaoxia Li,Xuran Lu,Rui He,Rongsong Xu,Muxin Gong
The present work seeks to construct a nanovehicle for the efficient suppression of breast cancer metastasis through targeting E-selectin on tumor vascular endothelial cells and hyaluronic acid-receptor on tumor cells. Herein, a new ligand-PEG-lipid conjugate, E-selectin binding peptide-polyethene glycol-1-octadecylamine (Esbp-PEG-OA), was used as the targeting molecule of micelle self-assembled form hyaluronic acid-paclitaxel (HA-PTX) conjugate. When loaded with free PTX, the micelles (Esbp-HA-PTX/PTX) exhibited nanoscale particle size with high drug-loading capacity (up to 31.5%). In vitro release study showed that the conjugated and entrapped PTX released simultaneously. Cellular uptake of micelles confirmed that Esbp-HA-PTX micelles could be specifically and efficiently internalized into E-selectin expressing human umbilical vein endothelial cells (HUVEC) and 4T1 breast cancer cells via receptor-meditated endocytosis. In vitro cytotoxicity assay further revealed that Esbp-HA-PTX/PTX micelles significantly improved the selectivity of PTX for killing the two cell types compared with PTX solution formulation. More importantly, Esbp-HA-PTX micelles raised the accumulation of payload in tumor through targeting two cell types in the tumor microenvironment simultaneously, resulting in marked in vivo inhibition of tumor growth, intratumoral microvessel density and metastasis, and decreased systemic toxicity over solution formulation. Overall, Esbp-HA-PTX/PTX micelle is promising in therapy of breast cancer metastasis.
研究领域:
药理学
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肿瘤学
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纳米技术
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生物医学工程
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2016
·
IF 3.773
Fangrong Zhang,Xiaoyi Wang,Xiangting Xu,Min Li,Jianping Zhou,Wei Wang
In the past decades, reconstituted high density lipoprotein (rHDL) has been successfully developed as a drug carrier since the enhanced HDL-lipids uptake is demonstrated in several human cancers. In this paper, rHDL, for the first time, was utilized to co-encapsulate two hydrophobic drugs: an anticancer drug , paclitaxel (PTX), and a new reversal agent for P-gp (P-glycoprotein)-mediated multidrug resistance (MDR) of cancer, N -cyano-1-[(3,4-dimethoxyphenyl)methyl]-3,4-dihydro-6,7-dimethoxy- N ′-octyl-2(1H)-isoquinoline-carboximidamide (HZ08). We proposed this drug co-delivery strategy to reverse PTX resistance. The study aimed to develop a biomimetic nanovector, reconstituted high density lipoprotein (rHDL), mediating targeted PTX-HZ08 delivery for cancer therapy. Using sodium cholate dialysis method, we successfully formulated dual-agent co-delivering rHDL nanoparticles (PTX-HZ08-rHDL NPs) with a typical spherical morphology, well-distributed size (~ 100 nm), high drug encapsulation efficiency (approximately 90%), sustained drug release properties and exceptional stability even after storage for 1 month or incubation in 10% fetal bovine serum (FBS) DMEM for up to 2 days. Results demonstrated that PTX-HZ08-rHDL NPs significantly enhanced anticancer efficacy in vitro , including higher cytotoxicity and better ability to induce cell apoptosis against both PTX-sensitive and -resistant MCF-7 human breast cancer cell lines (MCF-7 and MCF-7/PTX cells). Mechanism studies demonstrated that these improvements could be correlated with increased cellular uptake of PTX mediated by scavenger receptor class B type I (SR-BI) as well as prolonged intracellular retention of PTX due to the HZ08 mediated drug-efflux inhibition. In addition, in vivo investigation showed that the PTX-HZ08-rHDL NPs were substantially safer, have higher tumor-targeted capacity and have stronger antitumor activity than the corresponding dosage of paclitaxel injection. These findings suggested that rHDL NPs could be an ideal tumor-targeted nanovector for simultaneous transfer of insoluble anticancer drug and drug resistance reversal agents. The PTX-HZ08-rHDL NPs co-delivery system might be a new promising strategy to overcome tumor drug resistance.
研究领域:
药学
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肿瘤学
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纳米技术
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药物递送系统
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癌症生物学
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DOI
PubMed
高影响因子
CURRENT ORGANIC SYNTHESIS
·
2021
·Vol. 18
·期 6
·587-591
·
IF 1.975
Song Zurong,Lu Qin,Tao Ali,Wu Tianchen
Background: Paclitaxel, a natural diterpenoid compound, has anti-tumor effect by acting on tubulin, whereas coumarin, another kind of natural product, has anti-tumor effect, along with some other effects, such as anti-bacterial-., Moreover, it also possesses fluorescence. Objective:
Multi targeting is an effective strategy in drug design to combat tumor. Therefore, a combination of paclitaxel with other active molecular drugs for exploring the novel lead with multi-functions is in demand. Materials and Methods: To synthsize paclitaxel-coumarin conjugate via click
chemistry and to investigate anticancer activity by MTT assay and the scratch test. Results and Discussion: The results of MTT assay showed that compared tothe paclitaxel, the anti-tumor activity of the conjugate was significantly improved. The results of flow cytometry showed that the
conjugate had a stronger ability to induce apoptosis. The scratch test results showed that the conjugate had better anti- metastasis ability than paclitaxel. Conclusion: These findings indicated that paclitaxel and coumarin had a synergistic effect, which paved the way for the development
of paclitaxel through fluorescence.
研究领域:
药理学
·
肿瘤学
·
药物化学
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DOI
PubMed
高影响因子
COLLOID AND POLYMER SCIENCE
·
2016
·Vol. 295
·期 1
·1-12
·
IF 1.89
Qi Peilan,Bu Yongqiang,Xu Jing,Qin Benkai,Luan Shujuan,Song Shiyong
Many tumor cells have acidic microenvironment that can be exploited for the design of pH-responsive drug delivery systems. In this work, well-defined pH-sensitive and biodegradable polymeric micelles were prepared and evaluate as carrier of paclitaxel (PTX). A diblock copolymer constituting of a poly(ethylene glycol) (PEG) and a polycaprolactone (PCL) segment linked by a pH-sensitive hydrazone bond (Hyd), which was denoted as mPEG-Hyd-PCL, was synthesized. The copolymer was assembled to micelles with mean diameters about 100 nm. The mean diameters and size distribution of the hydrazone-containing micelles increased obviously in mildly acidic environments while kept unchanged in the neutral. No significant change in size was found on polymeric micelles without hydrazone (mPEG-PCL). PTX was loaded into micelles, and the anticancer drug released from mPEG-Hyd-PCL micelles was promoted by the increased acidity. In vitro cytotoxicity study showed that the PTX-loaded mPEG-Hyd-PCL micelles exhibited significantly enhanced cytotoxicity against HepG2 cells compared to the non-sensitive mPEG-PCL micelles. These results suggest that hydrazone-containing copolymer micelles with pH sensitivity and biodegradability show excellent potential as carriers of anticancer drugs.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
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DOI
高影响因子
Regenerative Biomaterials
·
2021
·Vol. 8
·期 3
·
IF 6.353
Wang Qiaoying,Wu Changqiang,Li Xiaoting,Yang Dixiao,Shi Liangjun
We have designed and developed an effective drug delivery system using biocompatible polymer of poly (ethylene glycol)-polyaspartic acid (mPEG-PAsp) for co-loading the chemotherapy drugs paclitaxel (PTX) and cisplatin (CP) in one nano-vehicle. This study aimed to improve the anti-cancer efficacy of combinations of chemotherapy drugs and reduce their side effects. mPEG-PAsp-(PTX/Pt) nano-micelles disperse well in aqueous solution and have a narrow size distribution (37.8 ± 3.2 nm) in dynamic light scattering (DLS). Drug release profiles found that CP released at pH 5.5 was significantly faster than that at pH 7.4. MPEG-PAsp-(PTX/Pt) nano-micelles displayed a significantly higher tumor inhibitory effect than mPEG-PAsp-PTX nano-micelles when the polymer concentrations reached 50 μg/mL. Our data indicated that polymer micelles of mPEG-PAsp loaded with the combined drug exert synergistic anti-tumor efficacy on SKOV3 ovarian cells via different action mechanisms. Results from our studies suggested that mPEG-PAsp-(PTX/Pt) nano-micelles are promising alternatives for carrying and improving the delivery of therapeutic drugs with different water solubilities.
研究领域:
药学
·
肿瘤学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Bo Hu,Ying Yan,Fei Tong,Long Xu,Jia Zhu,Guangtao Xu,Ruilin Shen
Background Lumbrokinase (LK) is an enzyme complex with antithrombotic, antioxidant, antitumor, and immunomodulatory effects. It has been extensively studied and used in clinical anti-tumor therapy. However, its half-life is short, its bioavailability is low, and its toxicity and side effects are great, which greatly limit its clinical application. Therefore, LK is often combined with other drugs (such as immune agents, hormones, or Chinese herbal medicine) to reduce its dosage and side effects and to improve its anti-tumor effects.Methods and results Here, we described an LK/paclitaxel (PTX) nanocarrier based on poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(ε-benzyoxycarbonyl-l-lysine)-r-poly(l-lysine)) (PEG-b-(PELG-g-(PZLL-r-PLL))). In the present study, LK and PTX were loaded by electrostatic and/or hydrophobic effects under mild conditions, thereby increasing the half-life and bioavailability of the drugs via the sustained release and enhancement of tumor site enrichment by the LK/PTX/PEG-b-(PELG-g-(PZLL-r-PLL)) complex through passive targeting. In this study, using bladder cancer cells (J82 cells) and rat bladder cancer model as the object, the structure of the nanocarrier, the relationship between drugs composition and antitumor properties were systematically studied.Conclusion We propose that the block copolymer PEG-b-(PELG-g-(PZLL-r-PLL)) may function as a potent nanocarrier for augmenting anti-bladder cancer pharmacotherapy, with unprecedented clinical benefits.
研究领域:
药学
·
肿瘤学
·
纳米技术
·
生物医学工程
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Xuling Chen,Jianbo Ji,Ke Zhou,Xiaohui Fan,Lingbing Li,Wei Xu
Despite its high antitumor activity , the clinical application of chemotherapy is greatly impeded by lacking of specific accumulation and poor solubility. To address the above challenges, we designed a AS1411 aptamer modified nanoparticles based on molecular recognition of nucleobases . Firstly, a redox sensitive Paclitaxel-SS-Zidovudine (PZ) prodrug was synthesized. Then PZ/β-lapachone/AS1411/DSPE-PEG nanoparticles were prepared and AS1411 aptamer was connected through molecular recognition between the nucleoside analogue Zidovudine (ZDV) and the thymine on aptamer. DSPE-PEG (DP) was incorporated into nanoparticles to prolong the residence time of nanoparticles in the blood circulation . Furthermore, to realize the combination treatment, β-lapachone (LAP) has been incorporated into nanoparticles with high drug loading efficiency through the interaction of π-π stacking force and H-bonding between LAP and Paclitaxel (PTX). LAP can generate abundant exogenous reactive oxygen species (ROS) via the bioactivation of NAD(P)H: quinone oxidoreductase-1 (NQO1). Moreover, the connection of Zidovudine (ZDV) and AS1411 through molecular recognition of nucleobases further optimized the nanoparticles with high affinity to nucleolin which overexpressed on tumor cell membrane , thereby inducing the specific accumulation of nanoparticles in tumor sites. In vivo and in vitro studies showed that the obtained nanoparticles of PZ/LAP/AS1411/DP exhibited better tumor growth inhibition and lower systemic side effects. Herein, we have rationally conducted a novel self-codelivery system for effectively synergistic antitumor treatment.
研究领域:
药理学
·
纳米技术
·
癌症研究
·
药物递送系统
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DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2023
·Vol. 19
·期 12
·2045-2059
·
IF 2.9
Yang Bowen,Huang Luyao,Zhou Zishuo,Yin Shanmei,Xi Mingrong
We aimed to develop an ovarian cancer-directed drug delivery system based on the high affinity of hyaluronic acid for CD44. The effects and mechanisms of hyaluronic acid-containing nanoparticles were investigated. The expression of CD44 in ovarian cancer was also determined. Hyaluronic
acid polymerized nanoparticles (HANPs), FITC-HANPs, and paclitaxel (PTX)-HANPs were prepared, and their characteristics were evaluated. The in vitro targetability and cytotoxicity properties of PTX-HANPs were evaluated through in vitro drug uptake and cytotoxicity assays. The
mechanisms of PTX-HANPs activity were investigated by apoptosis, wound healing, and Transwell invasion assays. In vivo targeting properties of HANPs were observed using a mouse ID8 subcutaneous model. in vitro experiments revealed an improved uptake of FITC-HANPs. The cytotoxicity
of PTX-HANPs in A2780/CP70 and ID8 cells was higher than that of PTX alone. PTX-HANPs increased cell apoptosis in a dose-dependent manner and exhibited a similar ability as PTX to inhibit cell migration. Furthermore, HANPs did not promote A2780/CP70 or ID8 cell migration and showed limited
inhibitory effects on their invasion. In vivo drug tracing experiments demonstrated the targetability of FITC-HANPs. In conclusion, PTX-HANPs improved PTX targetability and exhibited potent tumor-specific therapeutic activities. It may be considered a promising formulation for the preclinical
development of agents targeting epithelial ovarian cancer.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
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DOI
高影响因子
PHARMACEUTICAL BIOLOGY
·
2016
·
IF 1.546
Huihui Yuan,Bo Sun,Feng Gao,Minbo Lan
Context: Paclitaxel (PTX) is widely used in chemotherapy for cancer treatment; however, it has some serious side effects. Andrographolide (Andro) is a potential cancer therapeutic agent isolated from Andrographis paniculata (Burm. f.) Nees (Acanthaceae).Objective: The objective of this study is to evaluate the effects of PTX combined with Andro against A549 cells.Materials and methods: The effects of 24–48 h treatment with 0.48–60.75 nM PTX and 5.10–328.0 μM Andro on cellular proliferation, apoptosis, cell cycle and intracellular reactive oxygen species (ROS) were determined by sulphorhodamine B assay, Annexin V-FITC/PI apoptosis detection, PI staining and ROS assay, respectively. Synergy was determined using combination index. The antitumour efficacy of 20 mg/kg PTX with 100 mg/kg Andro was studied in a xenograft murine model.Results: IC50 value of the PTX combined with Andro against A549 cells was 0.5–7.4 nM, which was significantly lower than that of PTX (15.9 nM). PTX with 10 μM Andro caused (1.22–1.27)-fold apoptosis and 1.7-fold ROS accumulation compared with PTX alone. N-Acetylcysteine, a ROS scavenger, blocked this synergy in vitro. In contrast, G2/M phase cell cycle arrest resulting from PTX was not potentiated by Andro. Moreover, PTX in combination with Andro inhibited the growth of A549 transplanted tumours by 98%.Discussion and conclusion: The results indicate that the combination of PTX and Andro exert significant synergistic anticancer effect on A549 cells in vitro and in vivo. The synergy may be the result of the accumulation of ROS. The combination of Andro and PTX represents a potential strategy for the treatment of A549 cells.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症研究
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DOI
PubMed
高影响因子
Biomaterials Advances
·
2024
·
IF 5.5
Rongli Chen,Ergang Liu,Yuefei Fang,Nan Gao,Meng Zhang,Xiaoru Zhang,Wanying Chen,Chuxin Liang,Yu Zhang,Yongzhuo Huang
The marketed paclitaxel (PTX) formulation Taxol relies on the application of Cremophor EL as a solubilizer. The major drawback of Taxol is its hypersensitivity reactions and a pretreatment of anti-allergic drugs is a necessity. Therefore, developing an efficient and safe delivery vehicle is a solution to increase PTX treatment outcomes with minimal adverse effects. In this work, we prepared the amphiphilic peptides (termed AmP) from soybean proteins using a facile two-step method. AmP could efficiently solubilize PTX by self-assembling into mixed micelles with D-α-tocopherol polyethylene glycol succinate (TPGS), a common pharmaceutical expedient (PTX@TPGS-AmP). The intravenously administrated PTX@TPGS-AmP exhibited a slow clearance (0.24 mL·(min·kg) −1 ) and an enhanced AUC (41.4 μg.h/mL), manifesting a 3.6-fold increase compared to Taxol. In a murine 4T1 tumor model, PTX@TPGS-AmP displayed a superior antitumor effect o v er Taxol. Importantly, safety assessment showed a high biocompatibility of AmP and an i.v. dose up to 2500 mg/kg led to no observable abnormalities in the mice. In summary, the AmP presents a new green and easily-prepared amphiphilic biomaterial, with promising potential as a pharmaceutical excipient for drug delivery.
研究领域:
药学
·
肿瘤学
·
药物递送系统
·
生物技术
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2026
·
IF 14.1
Bo Chen,Yangyi Wang,Tingting Li,Changqing Guo,Zhe Xie,Zhixian Zhang,Xinghua Han,Wei Wang,Jian Wang,Xiaopeng Ma,Yuanzeng Min
Drug resistance in solid tumors has emerged as a critical challenge, with limited effective therapeutic options available. In this study, we find that chemotherapy induces an increased tumor neoantigens burden (TNB) in breast cancer patients and both non‐resistant and chemo‐resistant triple‐negative breast cancer 4T1 tumor‐bearing mice. Consistently, proteomic analysis reveals that tumor antigens derived from in vitro chemotherapy‐treated paclitaxel (PTX)‐resistant 4T1 cells (chemo‐rAg) are enriched in damage‐associated molecular patterns and neoantigens, highlighting their potential to elicit antitumor immunity against chemo‐resistant tumors. Based on these findings, we utilize the feature of PTX resistance and develop a nanovaccine incorporating chemo‐rAg and a prodrug of a toll‐like receptor 7 (TLR7) agonist. In preclinical mouse models, the nanovaccine effectively suppresses PTX‐resistant 4T1 tumor growth, and it also reverses the innate resistance of immune checkpoint inhibitors. Notably, the therapeutic benefit of the nanovaccine is augmented by chemotherapy, which facilitates in situ release of tumor antigens. These results suggest that a chemo‐rAg‐based nanovaccine represents a promising strategy based on the ′like cures like' principle to overcome drug resistance by utilizing the characteristic of the drug resistance itself. In the murine triple‐negative breast cancer (TNBC) model, chemotherapy effectively increases tumor neoantigen burden (TNB). Here, the study constructs a liposomal nanovaccine using antigens derived from in vitro chemotherapy‐treated paclitaxel‐resistant TNBC 4T1 cells. The combination of the nanovaccine and immune checkpoint inhibitor (ICI) potently suppresses the growth of subcutaneously implanted paclitaxel‐resistant 4T1 tumors, effectively overcoming the drug resistance.
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产品关联
DOI
PubMed
高影响因子
Chem & Bio Engineering
·
2026
·
IF 8.4
Ren Xitong,Jing Qitian,Sun Jiali,Kong Chaoying,Shen Na,Tang Zhaohui
Paclitaxel (PTX) remains a first-line
chemotherapeutic agent, yet
its therapeutic index is limited by poor tumor selectivity, nonspecific
biodistribution, and systemic toxicity. Here, we report an ultrasound
(US)-activated PTX prodrug nanoplatform (PTX@TBR NPs) for tumor-selective
and spatiotemporally controlled PTX activation. PTX was covalently
masked with a US-responsive thioketal (TK) linker and conjugated to
a polymer, while riboflavin tetrabutyrate (TBR), a vitamin B 2 -derived sonosensitizer, was coencapsulated to enable sonochemical
activation. Upon US irradiation, TBR generated singlet oxygen ( 1 O 2 ), which oxidized the TK linker and triggered
its cleavage, thereby enabling on-demand PTX release with an efficiency
of up to 68.0%. In vivo , PTX@TBR NPs+US achieved
potent tumor inhibition, with a tumor suppression rate of 80.1%. Unexpectedly,
this treatment also markedly suppressed distant metastasis. Transcriptomic
analysis revealed broad downregulation of genes associated with redox-related
metabolism, extracellular matrix remodeling, and lipid metabolic pathways,
suggesting that sonochemical activation and PTX release cooperatively
disrupted redox homeostasis, cytoskeletal functions, and metabolic
adaptation. This study establishes a sonochemically amplified prodrug
activation strategy for selective PTX chemotherapy and the inhibition
of tumor growth and metastasis.
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高影响因子
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