JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2023
·
IF 3
Peng Qi,Ping Li,Lijiao Qiao,Huaqian Xue,Yanni Ma,Shijie Wei,Xiaoying Yang,Hao Zhang,Yuxin Zhang,Yifan Wang,Shaolong He,Hongfeng Quan,Wenping Zhang
Pirarubicin (THP), doxorubicin (DOX), cyclophosphamide (CTX), and vincristine (VCR) are widely used in the treatment of patients with non-Hodgkin's Lymphoma. Herein, a precise and sensitive method was developed for the determination of THP, DOX, CTX and VCR in human plasma by high-performance liquid-chromatography–tandem mass spectrometry (LC-MS/MS). Liquid-liquid extraction was applied to extract THP, DOX, CTX, VCR, and the internal standard (IS, Pioglitazone) in plasma. Agilent Eclipse XDB-C18 (3.0 mm × 100 mm) was utilized and chromatographic separation was obtained in eight minutes. Mobile phases were composed of methanol and buffer (10 mM ammonium formate containing 0.1% formic acid). The method was linear within the concentration range of 1–500 ng/mL for THP, 2–1000 ng/mL for DOX, 2.5–1250 ng/mL for CTX, and 3–1500 ng/mL for VCR. The intra- and inter-day precisions of QC samples were found to be below 9.31 and 13.66%, and accuracy ranged from −0.2 to 9.07%, respectively. THP, DOX, CTX, VCR and the internal standard were stable in several conditions. Finally, this method was successfully utilized to simultaneously determine THP, DOX, CTX and VCR in human plasma of 15 patients with non-Hodgkin's Lymphoma after intravenous administration. Finally, the method was successfully employed in the clinical determination of THP, DOX, CTX, and VCR in patients with non-Hodgkin lymphoma after administration of RCHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Xiaoxia Yang,Pengfei Shang,Jianbo Ji,Christina Malichewe,Zhiyin Yao,Jing Liao,Dandan Du,Chao Sun,Lei Wang,Ya-jie Tang,Xiuli Guo
In this study, a chitosan-based, self-assembled nanosystem that codelivered microRNA34a (miR34a) and doxorubicin (Dox) with hyaluronic acid (HA) modification (named CCmDH NPs) was developed to reverse the resistance of breast cancer (BCa) cells to Dox. The CCmDH NPs had a diameter of 180 ± 8.3 nm and a ζ potential of 16.5 mV with a slow-release effect for 96 h. The codelivery system could protect miR34a from nuclease and serum degradation and transport miR34a and Dox into drug-resistant MCF-7/A cells. In addition, the CCmDH NPs could inhibit proliferation and promote apoptosis by regulating the protein expression of B-cell lymphoma-2 (Bcl-2) and poly(ADP-ribose) polymerase (PARP) and inhibit invasion, metastasis, and adhesion by regulating E-cadherin, N-cadherin, MMP2, CD44, and Snail molecules. The CCmDH NPs induced a 73.7% tumor reduction in xenograft tumor growth in nude mice in vivo. This study provides evidence for the anticancer activity of CCmDH NPs carrying Dox and miR34a in BCa, especially metastatic Dox-resistant BCa models.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Wenbo Wu,Xiaoli Yu,Jiaxiang Sun,Yuanyuan Han,Yuanye Ma,Guoqing Zhang,Qingming Ma,Qiang Li,Hongfei Xiang
Background As a broad-spectrum antitumorigenic agent, doxorubicin (DOX) is commonly used as a chemotherapeutic drug for treating osteosarcoma (OS). Still, it is associated with significant cell toxicity and ineffective drug delivery, whereas the zeolite imidazolate framework is extensively applied in the biomedical field as a carrier owing to its favorable biocompatibility, high porosity, and pH-responsiveness. Therefore, we need to develop a drug delivery platform that can effectively increase the antitumorigenic effect of the loaded drug and concurrently minimize drug toxicity.Methods In this study, a Fe3O4@ZIF-8 nanocomposite carrier was prepared with ZIF-8 as the shell and encapsulated with Fe3O4 by loading DOX to form DOX- Fe3O4@ZIF-8 (DFZ) drug-loaded magnetic nanoparticles. Then, we characterized and analyzed the morphology, particle size, and characteristics of Fe3O4@ZIF-8 and DFZ by TEM, SEM, and Malvern. Moreover, we examined the inhibitory effects of DFZ in vitro and in vivo. Meanwhile, we established a tumor-bearing mouse model, evaluating its tumor-targeting by external magnetic field guidance.Results DFZ nanoparticles possessed have a size of ~110 nm, with an encapsulation rate of 21% and pH responsiveness. DFZ exerted a superior cytostatic effect and apoptosis rate on K7M2 cells in vitro compared to DOX(p<0.01). In animal experiments, DFZ offers up to 67% tumor inhibition and has shown a superior ability to induce apoptosis than DOX alone in TUNEL results(p<0.01). Tumor-targeting experiments have validated that DFZ can be effectively accumulated in the tumor tissue and enhance anticancer performance.Conclusion In summary, the DFZ nano-delivery system exhibited a more substantial anti-tumorigenic effect as well as superior active tumor targeting of DOX- Fe3O4@ZIF-8 compared to that of DOX alone in terms of biocompatibility, drug loading capacity, pH-responsiveness, tumor-targeting, and anti-tumorigenic effect, indicating its chemotherapeutic application potential.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2021
·Vol. 11
·期 15
·9021-9028
·
IF 3.361
Meifang Wang,Jing Lin,Jiawei Gong,Mingchen Ma,Hongliang Tang,Jiyang Liu,Fei Yan
Direct and accurate detection of doxorubicin (DOX) in unprocessed human whole blood is of vital importance in medical diagnosis and monitoring. In this work, we demonstrate the utilization of electrochemically pretreated glassy carbon electrodes (p-GCE) modified with vertically-ordered mesoporous silica films (VMSF) for rapid and sensitive electrochemical detection of DOX. The electrochemically pretreated process is a simple, cost-effective and environmentally friendly approach for improving interface catalytic properties and introducing oxygen-containing groups into the GCE surface, which could be suitable for stably growing VMSF without any adhesive layer simultaneously retaining the underlying electrode activity. Benefiting from the highly sensitive electrode substrate of p-GCE and electrostatic preconcentration effect of VMSF, the present VMSF/p-GCE sensor was able to determine DOX with an ultrahigh sensitivity (23.94 μA μM−1) and a relatively low limit of detection (0.2 nM) and a rather wide linear range (0.5 nM to 23 μM). Furthermore, direct and reliable electrochemical detection of DOX in human whole blood without complicated sample pretreatments was achieved owing to the excellent anti-fouling and anti-interference ability of VMSF.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2021
·Vol. 21
·期 6
·2100049
·
IF 4.979
Yingge Shi,Dong Li,Chaoliang He,Xuesi Chen
Combination therapy can be used to enhance the therapeutic response and decrease side effects during cancer treatment. In this study, a system is developed to locally deliver the immune checkpoint blockade antibody targeting programmed death-ligand 1 (anti-PD-L1 or aPD-L1) and doxorubicin (Dox), by an injectable, biocompatible polypeptide hydrogel as a drug depot. The localized and sustained release of Dox after the intratumoral injection of the co-loaded hydrogel induces immunogenic tumor cell death, thus promoting an antitumor immunological response. The tumor inhibitory effect is significantly enhanced by the simultaneous release of aPD-L1 at the tumor site thanks to its action on the inhibition of the PD-1/PD-L1 pathway and restoration of the tumor-killing effect of cytotoxic T cells. Treatment of the B16F10 melanoma model with the aPD-L1 and Dox co-loaded hydrogel leads to a remarkable inhibition of tumor progression and prolongation of animal survival.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2019
·
IF 2.606
Meijia Song,Yan Liang,Keke Li,Jing Zhang,Nan Zhang,Baocheng Tian,Jingtian Han
Tumor targeted drug delivery system has been developed as a promising approach to improve cancer chemotherapy . The design of hyaluronic acid (HA)-modified nanocarriers has been proven to be effective for targeting CD44 overexpressing tumor cells. Moreover, combination therapy can improve the therapeutic effect and delay the development of drug resistance. In this study, doxorubicin (DOX) and paclitaxel (PTX) co-loaded liposomal delivery system modified with an acid-cleavable cholesterol-HA conjugate (Chol-HA) was prepared by post-insertion method. The dual-drug co-loaded HA modified liposome (HA-D/P-Lip), had a suitable particle size of 125.5 ± 0.79 nm with negative surface charge of −9.56 ± 0.62 mV, and acceptable encapsulation efficacy of 93.6 ± 0.51% (DOX) and 70.4 ± 1.46% (PTX). In vitro drug release study showed that the cumulative release of both drugs over 72 h were much higher in pH 5.5 phosphate buffer than that in pH 7.4 phosphate buffer. In vitro cytotoxicity study against MCF-7 breast cancer cells illustrated superior cytotoxicity and obvious synergistic effect in comparison to free drug or single drug loaded liposome via MTT assay. In vitro cellular uptake study demonstrated a higher cell internalization of HA-DOX-Lip compared with DOX loaded non-modified liposome (DOX-Lip) and free DOX. Therefore, the pH-sensitive HA-targeted liposome may be a useful targeted nanocarrier for efficient tumor therapy.
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2019
·
IF 4.396
Yilin Chen,Qing Chen,Qixin Zhu,Jinxue Liu,Yang Li,Xuemin Gao,Dengyue Chen,Xuan Zhu
Because of high drug payload and minimized burden of foreign materials in the course of metabolism and excretion, carrier-free nanomedicine based on self-assembly of small-molecule therapeutic agents has attracted considerable attention in cancer therapy. However, obstacles still remained, such as lack of targeting efficiency, poor physiological stability, and serious drug burst release. Herein, we developed a self-dual-targeting prodrug conjugate by coupling methotrexate (MTX) and doxorubicin (DOX) to a hyaluronic acid (HA) backbone which enveloped the small molecular drug coassemblies of DOX and indocyanine green for specific targeting and imaging-guided chemo-photothermal therapy (PTT). The constructed nanosystems exhibited a diameter of ∼200 nm, superior physiological stability, and improved photothermal effect. Taking advantage of functionality of MTX–HA–DOX conjugate, the nanosystems remarkably enhanced the accumulation in the tumor regions by enhanced penetration and retention effect and CD44/folate receptor-mediated endocytosis. Upon the stimuli of acid, the nanosystems showed the rapid disassembly followed by the accelerated drug release. Consequently, the nanosystems demonstrated highly efficient apoptosis in cancer cells and remarkable tumor ablation by synergy between chemotherapy and PTT upon the irradiation of near-infrared laser. The multifunctional nanosystems based on small molecular theranostic assemblies could provide a promising potential in developing dual-targeting drug delivery and imaging-guided combinational therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2019
·
IF 10.273
Yanlin Feng,Yan Cheng,Yun Chang,Hui Jian,Runxiao Zheng,Xiaqing Wu,Keqiang Xu,Li Wang,Xiaomin Ma,Xi Li,Haiyuan Zhang
Photochemotherapy is currently an effective anticancer therapy. Recently, it has been reported that cancer cells pretreated with epidermal growth factor receptor (EGFR) inhibitor erlotinib (Erl) can significantly synergize its apoptosis against the DNA damaging agent doxorubicin (Dox). As a result, we designed two gold nanocages (Au NCs) microcontainers covered with different smart polymer shell-PAA (pH responsive) and p (NIPAM-co-AM) (temperature responsive) containing Erl and Dox respectively. The acidic tumor microenvironment and NIR light irradiation can selectively activate the release of Erl and Dox. Time staggered release of Erl and Dox and photothermal therapy enhance the apoptotic signaling pathways , resulting in improved tumor cell killing in both MCF-7 (low EGFR expression) and A431 (very high EGFR expression) tumor cells, but more efficient in the latter. The photochemotherapy strategy controls the order and duration of drug exposure precisely in spatial and temporal, and significantly improves the therapeutic efficacy against high EGFR expressed tumors.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2019
·
IF 2.347
Xu-Feng Wang,Jin Ren,Hai-Qing He,Liang Liang,Xin Xie,Zi-Xin Li,Jian-Guo Zhao,Jing-Mou Yu
In this study, reduction-sensitive self-assembled polymer nanoparticles based on poly (lactic-co-glycolic acid) (PLGA) and chondroitin sulfate A (CSA) were developed and characterized. PLGA was conjugated with CSA via a disulfide linkage (PLGA-ss-CSA). The critical micelle concentration (CMC) of PLGA-ss-CSA conjugate is 3.5 µg/mL. The anticancer drug doxorubicin (DOX) was chosen as a model drug, and was effectively encapsulated into the nanoparticles (PLGA-ss-CSA/DOX) with high loading efficiency of 15.1%. The cumulative release of DOX from reduction-sensitive nanoparticles was only 34.8% over 96 h in phosphate buffered saline (PBS, pH 7.4). However, in the presence of 20 mM glutathione-containing PBS environment, DOX release was notably accelerated and almost complete from the reduction-sensitive nanoparticles up to 96 h. Moreover, efficient intracellular DOX release of PLGA-ss-CSA/DOX nanoparticles was confirmed by CLSM assay in A549 cells. In vitro cytotoxicity study showed that the half inhibitory concentrations of PLGA-ss-CSA/DOX nanoparticles and free DOX against A549 cells were 1.141 and 1.825 µg/mL, respectively. Therefore, PLGA-ss-CSA/DOX nanoparticles enhanced the cytotoxicity of DOX in vitro. These results suggested that PLGA-ss-CSA nanoparticles could be a promising carrier for drug delivery.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2020
·Vol. 12
·期 4
·2673-2685
·
IF 6.895
Yang Li,Yimin Niu,Jianhua Zhu,Cuicui Gao,Qunwei Xu,Zhiyu He,Dawei Chen,Ming Xu,Yang Liu
Legumain enzyme is a well-conserved lysosomal cysteine protease and is over-expressed in many tumor cells and tumor stromal cells and exhibits higher protease activity under acidic conditions, such as in lysosomes and endosomes. Legumain enzyme-triggered drug delivery systems have demonstrated potential therapeutic values in cancer targeted therapy. To realize a more efficient delivery of anticancer therapeutic agents, we herein report a legumain/pH dual-responsive drug delivery system for enhancing site-specific controlled release of antitumor drugs. The carrier (named “DS-NA”) is a hybrid vector constituting PEG-b-PBLA polymers, pH-responsive OAPI polymers, and legumain-sensitive peptide-doxorubicin prodrug decorated fluorescent carbon dots (CDs-C9-AANL-DOX). In tumor cells, DS-NA could disassemble rapidly in acidic environments, and then release doxorubicin through legumain digestion. Except as a drug vector, the drug release process from DS-NA could also be dynamically monitored by CLSM as the DOX was released from the surface of CDs through the AANL peptide linker digested by legumain, then transferred into the cell nucleus and exerted cytotoxicity, while the CDs themselves remained in the cytoplasm. As a control, the CDs-C9-DOX, which did not contain the AANL peptide linker, also still resided in the cytoplasm. Furthermore, in vivo studies show that DS-NA had a stronger inhibitory effect on tumor tissue with attenuated side effects to normal tissues than control nanoparticles or free drugs, which may be due to comprehensive effects including pH/legumain dual-triggered drug release, long blood circulation periods, and EPR effects. Together, a combination strategy of acid sensitivity and legumain enzyme sensitivity used for site-specific controlled release of drugs provides a novel method for enhanced and precise antitumor chemotherapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 115
·94719-94731
·
IF 3.84
Lili Chen,Xiaohong Wang,Fangling Ji,Yongming Bao,Jingyun Wang,Xianwu Wang,Lianying Guo,Yachen Li
Combined treatment of drugs and therapeutic genes has emerged as a new modality of anticancer therapy. In this study, a new amphiphilic bifunctional pullulan derivative (named as PSP) containing stearic acid and low-molecular weight (1 kDa) branched polyethylenimine was prepared and evaluated as a nano-carrier for the co-delivery of a drug and gene for potential cancer therapy. The amphiphilic PSP could self-assemble into cationic core–shell nano-micelles in water, with a critical micelle concentration of around 58.9 mg L−1. PSP nanomicelles had an average size of 188.75 ± 3.18 nm, and a positive zeta potential of 17.83 ± 0.75 mV. The drug loading content and encapsulation efficiency of the PSP nanomicelles for doxorubicin (DOX), an anti-tumor drug, were about 5.10% and 56.07%, respectively, and DOX in PSP nanomicelles showed sustained release. The flow cytometry and confocal laser scanning microscopy showed that PSP/DOX nanomicelles could be successfully internalized by MCF-7 cells. The in vitro IC50 of PSP/DOX nanomicelles was slightly lower than that of free DOX against MCF-7 cells. Additionally, PSP nanomicelles condensed DNA efficiently to form compact structures, and induced comparable GFP gene expression level to Lipo2000 at N/P = 10 in gene transfection studies. In comparison with single DOX or p53 delivery, the co-delivery of DOX and therapy gene p53 using PSP micelles displayed higher cytotoxicity and induced a higher apoptosis rate of tumor cells in vitro. Moreover, PSP exhibited good blood compatibility and low cytotoxicity in the hemolysis and MTT assays, respectively. Altogether, PSP nanomicelles have a great potential in delivering hydrophobic anticancer drugs and therapeutic genes simultaneously for improved cancer therapy.
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 19
·3531-3540
·
IF 4.543
Hao Zhu,Yun Wang,Abid Hussain,Zhipeng Zhang,Yuanyuan Shen,Shengrong Guo
Co-delivery of two or more chemotherapeutic agents via nanocarriers can provide an effective approach to maximize synergistic or additive effects. In this work, we developed novel nanodiamond (ND) based nanoparticle co-loading of doxorubicin (DOX) and malaridine (MAL) for treatment of MCF-7/ADR cells by virtue of the good biocompatibility, high drug loading capacity and pH-responsive drug release properties of NDs. The combination index (CI) was the smallest, 0.17, for DOX and MAL against MCF-7/ADR cells, when their ratio was 5 : 1, showing the greatest synergistic effects. (DOX + MAL)@NDs or FA-PEG–DOX/(DOX + MAL)@NDs with different ratios of DOX to MAL (4 : 1, 5 : 1 and 6 : 1) were prepared by simple physical adsorption of DOX, MAL and FA-PEG–DOX. Among them, (DOX + MAL)@NDs with the mass ratio of 5 : 1 had the smallest CI of 0.08. The concentrations of DOX and MAL for (DOX + MAL)@NDs producing 50% growth inhibition were 1.90 and 0.35 μg mL−1, respectively, smaller than the 50% inhibitory concentrations for DOX@NDs and MAL@NDs (10.75 and 4.38 μg mL−1) and for free DOX and free MAL (49.65 and 9.03 μg mL−1). (DOX + MAL)@NDs were not stable in water, FA-PEG–DOX/(DOX + MAL)@NDs could stay stable in water for 24 h due to steric repulsion effects offered by PEG, which also compromised their cytotoxicities to some extent. (DOX + MAL)@NDs or FA-PEG–DOX/(DOX + MAL)@NDs presented faster DOX and MAL co-release at pH 5.5 than 7.4. The high anti-tumor efficacy suggested that the ND mediated DOX and MAL co-delivery system could be promising for the treatment of multi-drug resistant cancer.
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）