Journal of Biomedical Research
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2021
·
IF 0
Siwan Wang,Hui Jiang,Jia Wang,Haisi Wu,Ting Wu,Mengnan Ni,Qianqian Zhao,You Ji,Ziting Zhang,Chunming Tang,Huae Xu
As a well-known anticancer drug, paclitaxel (PTX), a first-line chemotherapeutic agent, remains unsatisfactory for gastric cancer therapy. It is reported that triptolide (TPL) could enhance the anti-gastric cancer effect of PTX. Considering the poor solubility of both drugs, we developed a red blood cell membrane-biomimetic nanosystem, an emerging tool in drug delivery, to co-load paclitaxel and triptolide (red blood cell membrane coated PTX and TPL co-loaded poly(lactic- co -glycolic acid) [PLGA] nanoparticles, RP(P/T)). The successful preparation was confirmed in terms of particle size, morphology, and surface markers assays. This biomimetic system could prolong circulation and escape immune surveillance. And these properties were verified by stability, in vitro drug release, and cellular uptake assays. Moreover, the MTT and colony formation assays demonstrated the superior anti-proliferation effect of the RP(P/T) to free drugs. The enhanced antitumor effects of RP(P/T) on migration and invasion were also evaluated by wound-healing and transwell assays. Overall, the bionic co-delivery nanoplatform with improved efficacy in vitro is a promising therapy for gastric cancer.
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DOI
PubMed
Materials Science & Engineering C-Materials for Biological Applications
·
2021
·
IF 7.328
QingQing Leng,Yue Li,Ping Zhou,Kang Xiong,Yun Lu,YongXia Cui,BiQiong Wang,ZhouXue Wu,Ling Zhao,ShaoZhi Fu
Post-operative recurrence and metastasis is a major challenge for breast cancer treatment. Local chemotherapy is a promising strategy that can overcome this problem. In this study, we synthesized an injectable hyaluronic acid (HA)-based hydrogel loaded with paclitaxel (PTX) nanoparticles and epirubicin (EPB) (PPNPs/ [email protected] ). PPNPs/ [email protected] steadily released the encapsulated drugs to achieve long-term inhibition of tumor recurrence and metastasis in a murine post-operative breast tumor model, which prolonged their survival without any systemic toxicity. The drug-loaded hydrogel inhibited the proliferation and migration of tumor cells in vitro , and significantly increased tumor cell apoptosis in vivo . Therefore, PPNPs/ [email protected] can be used as a local chemotherapeutic agent to prevent postoperative recurrence and metastasis of breast cancer.
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PubMed
高影响因子
Acta Pharmaceutica Sinica B
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2020
·
IF 7.097
Xinyu Lou,Dong Zhang,Hao Ling,Zhonggui He,Jin Sun,Mengchi Sun,Dongchun Liu
A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer. However, its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier. Herein, we report an albumin-bound tumor redox-responsive paclitaxel prodrugs nano-delivery strategy. Using diverse linkages (thioether bond and disulfide bond), paclitaxel (PTX) was conjugated with an albumin-binding maleimide (MAL) functional group. These pure PTX prodrugs could self-assemble to form uniform and spherical nanoparticles (NPs) in aqueous solution without any excipients. By immediately binding to blood circulating albumin after intravenous administration, NPs are rapidly disintegrated into small prodrug/albumin nanoaggregates in vivo , facilitating PTX prodrugs accumulation in the tumor region via albumin receptor-mediated active targeting. The tumor redox dual-responsive drug release property of prodrugs improves the selectivity of cytotoxicity between normal and cancer cells. Moreover, disulfide bond-containing prodrug/albumin nanoaggregates exhibit long circulation time and superior antitumor efficacy in vivo . This simple and facile strategy integrates the biomimetic characteristic of albumin, tumor redox-responsive on-demand drug release, and provides new opportunities for the development of the high-efficiency antitumor nanomedicines.
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PubMed
高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Lv Lingyan,Li Xinrui,Qian Wei,Li Shennan,Jiang Yan,Xiong Yaokun,Xu Jianpei,Lv Wei,Liu Xiaoyan,Chen Yun,Tang Yulin,Xin Hongliang
The serious therapeutic obstacles to glioma treatment include poor penetration across the blood-brain barrier (BBB) and low accumulation of therapeutic drugs at tumor sites. In this study, borneol combined with CGKRK peptide (a ligand of the heparan sulfate which overexpress on the glioma cells) modified paclitaxel prodrug self-assembled redox-responsive nanoparticles (CGKRK-PSNPs) were hypothesized to enhance the BBB penetration ability and active tumor targeting efficiency, respectively. The resulting CGKRK-PSNPs possessed a spherical shape with a small particle size (105.61 ± 1.53 nm) and high drug loading for PTX (54.18 ± 1.13%). The drug release behavior proved that CGKRK-PSNPs were highly sensitive to glutathione (GSH) redox environment. The in vitro cell experiments suggested that CGKRK-PSNPs significantly increased the cellular uptake and cytotoxicity of U87MG cells, meanwhile CGKRK-PSNPs showed the low cytotoxicity against BCEC cells. Combined with borneol, CGKRK-PSNPs exhibited enhanced transportation across in vitro BBB model. In intracranial U87MG glioma-bearing nude mice, the higher accumulation of CGKRK-PSNPs combined with borneol was observed through real-time fluorescence image. Moreover, the in vivo anti-glioma results confirmed that CGKRK-PSNPs combined with borneol could improve the anti-glioma efficacy with the prolonged medium survival time (39 days). In conclusion, the collaborative strategy of CGKRK-PSNPs combined with borneol provided a promising drug delivery routine for glioblastoma therapy.
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PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2020
·
IF 4.321
Ping Zhong,Xuehong Chen,Rishuo Guo,Xiaomei Chen,Zhihao Chen,Cui Wei,Yusheng Li,Wanting Wang,Yi Zhou,Linghao Qin
The efflux of anticancer agents mediated by P-glycoprotein (P-gp) is one of the main causes of multidrug resistance (MDR) and eventually leads to chemotherapy failure. To overcome this problem, the delivery of anticancer agents in combination with a P-gp inhibitor using nanocarrier systems is considered an effective strategy. On the basis of the physiological compatibility and excellent drug loading ability of erythrocytes, we hypothesized that nanoerythrocytes could be used for the codelivery of an anticancer agent and a P-gp inhibitor to overcome MDR in breast cancer. Herein, a folic acid-modified nanoerythrocyte system (PTX/TQR NPs@NanoRBC-PEG/FA) was prepared to simultaneously transport paclitaxel and tariquidar, and the in vitro and in vivo characteristics of this delivery system were evaluated through several experiments. The results indicated that the average diameter and surface potential of this nanocarrier system were 159.8 ± 1.4 nm and −10.98 mV, respectively. Within 120 h, sustained release of paclitaxel was observed in both pH 6.5 media and pH 7.4 media. Tariquidar release from this nanocarrier suppressed the P-gp function of MCF-7/Taxol cells and significantly increased the intracellular paclitaxel level (p < 0.01 versus the PTX group). The results of the MTT assay indicated that the simultaneous transportation of paclitaxel and tariquidar could significantly inhibit the growth of MCF-7 cells or MCF-7/Taxol cells. After 48 h of incubation with PTX/TQR NPs@NanoRBC-PEG/FA, the viability of MCF-7 cells and MCF-7/Taxol cells decreased to 7.37% and 30.2%, respectively, and the IC50 values were 2.49 μM and 6.30 μM. Pharmacokinetic results illustrated that, compared with free paclitaxel, all test paclitaxel nanoformulations prolonged the drug release time and showed similar plasma concentration–time profiles. The peak concentration (Cmax), area under the curve (AUC0–∞), and half-life (t1/2) of PTX/TQR NPs@NanoRBC-PEG/FA were 3.33 mg/L, 6.02 mg/L·h, and 5.84 h, respectively. Moreover, this active targeting nanocarrier dramatically increased the paclitaxel level in tumor tissues. Furthermore, compared with those of the other paclitaxel formulations, the cellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels of the PTX/TQR NPs@NanoRBC-PEG/FA group increased by 1.38-fold (p < 0.01) and 1.36-fold (p < 0.01), respectively, and the activities of superoxide dismutase (SOD) and catalase (CAT) decreased to 67.8% (p < 0.01) and 65.4% (p < 0.001), respectively. More importantly, in vivo antitumor efficacy results proved that the PTX/TQR NPs@NanoRBC-PEG/FA group exerted an outstanding tumor inhibition effect with no marked body weight loss and fewer adverse effects. In conclusion, by utilizing the inherent and advantageous properties of erythrocytes and surface modification strategies, this biomimetic targeted drug delivery system provides a promising platform for the codelivery of an anticancer agent and a P-gp inhibitor to treat MDR in breast cancer.
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PubMed
高影响因子
APPLIED SURFACE SCIENCE
·
2024
·
IF 6.3
Wenlong Li,Yuanhu Tang,Zirui Zhao,Yajing Zhang,Shujie Wang
Paclitaxel (PTX), an active anticancer compound derived from Taxus cuspidata , possesses considerable economic value. Given the abundance of structural analogs, the selective separation of PTX from T. cuspidata presents a formidable challenge. In this study, the bifunctional monomers magnetic molecular imprinted polymers (MMIPs) with multiple active sites were synthesized using Fe 3 O 4 as the magnetic carrier, PTX as the template, 4-vinylpyridine (4-VP) and methacrylic acid (MAA) as the first-stage and the second-stage pre-assembly functional monomer, respectively. The results indicated that MMIPs exhibited excellent magnetic recovery capability and high adsorption capacity for PTX. Furthermore, the adsorption behaviors were more consistent with Langmuir isotherm model and pseudo-second-order kinetic model. The MMIPs possessed significantly higher selectivity for PTX than five structural analogs (Docetaxel, Baccatin III, 10-Deacetylbaccatin III, and Glucose) and recyclability for up to six cycles. Additionally, the adsorption mechanism analysis indicated that the excellent performance of MMIPs primarily arises from the multiple active binding sites involving hydrogen bonding and π-π stacking. Finally, MMIPs were used for PTX recognition and separation in T. cuspidata extracts. This study provides an efficient method and valuable theoretical basis for the highly selective separation of PTX from T. cuspidata.
研究领域:
药物化学
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分析化学
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材料科学
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生物技术
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高影响因子
CARBOHYDRATE POLYMERS
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2019
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IF 6.044
Ding Qu,Mengying Jiao,Haijiao Lin,Chunli Tian,Guowei Qu,Jingwei Xue,Lingjing Xue,Caoyun Ju,Can Zhang
Controlled release and tumor-selective distribution are highly desirable for anticancer nanomedicines. Here, we design and synthesize an anisamide-conjugated N -octyl- N,O -maleoyl- O -phosphoryl chitosan (a-OMPC) which can form amphiphilic micelles featuring pH-responsive release and high affinity to sigma-1 receptor-overexpressed tumors for paclitaxel (PTX) delivery. Thereinto, maleoyl and phosphoryl groups cooperatively contribute to pH-responsive drug release due to a conversion from hydrophile to hydrophobe in the acidic microenvironment of endo/lysosomes. We demonstrated that PTX-loaded a-OMPC micelles (PTX-aM) enhanced the cellular internalization via the affinity between anisamide and sigma-1 receptor, rapidly released drug in endo/lysosomes and elevated the cytotoxicity against PC-3 cells. The in vivo studies further verified that PTX-aM could largely accumulate at the tumor site even after 24 h of administration, resulting in obvious inhibition effect and prolonged survival period in PC-3 tumor xenograft-bearing mice. Moreover, OMPC showed no obvious hemolytic and acute toxicity. Collectively, this chitosan derivate holds a promising potential in application of prostate cancer-targeted drug delivery system.
研究领域:
药剂学
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肿瘤学
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纳米医学
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PubMed
高影响因子
AAPS PHARMSCITECH
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2018
·Vol. 19
·期 5
·2395-2406
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IF 2.666
Xiao Yu,Wang Shuang,Zong Qingyu,Yin Zongning
Single chemotherapeutic agent like paclitaxel (PTX) has shown some limitations in anti-tumor treatment, such as undesirable side effects, multidrug resistance, and high toxicity. In order to reduce the toxicity of PTX and increase the anti-tumor effect, folate-modified amphiphilic and biodegradable biomaterial was developed to co-deliver PTX and metformin (MET) for exerting the synergistic effect. PTX was physically entrapped in the hydrophobic inner core of the amphiphilic block copolymer by a solvent evaporation method, whereas MET was chemically conjugated to the hydrophilic terminals of copolymer via a pH-sensitive cis -aconityl linkage (Cis). The in vitro release behaviors of the drugs were analyzed by high-performance liquid chromatography (HPLC), and the synergistic effect of the drugs was evaluated by a Q value method. Results showed that drug-loaded micelles with an average size about 100 nm were successfully constructed. In acidic environments, the chemically conjugated MET was rapidly released after the breakage of sensitive bond between drug and copolymer. In vitro anti-tumor studies demonstrated that MET and PTX had a synergistic effect and co-delivery micelles induced higher cytotoxicity and apoptosis against 4T1 breast cancer cells than free drugs. Furthermore, folate-targeted co-delivery micelles increased the cellular uptake of drugs and were found to be effective for the treatment of solid tumor in vivo . These findings indicated that co-delivery of MET and PTX through the polymeric micelles is a promising strategy for cancer therapy.
研究领域:
药剂学
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肿瘤学
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DOI
高影响因子
International Journal of Nanomedicine
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2020
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IF 5.115
Li He,Fangzhen Qing,Maode Li,Daitian Lan
Purpose The aim of this study was to develop an “all-in-one” nanoplatform that integrates at the second near-infrared (NIR-II) region dye IR1061 and anticancer drug paclitaxel (PTX) into an apoferritin (AFN) nanocage (IR-AFN@PTX). Simultaneously, folic acid (FA), tumor target molecule, was conjugated onto IR-AFN@PTX to be IR-AFN@PTX-FA for tumor-targeted and pH/NIR-II-triggered synergistic photothermal-chemotherapy.Methods IR1061 was firstly reacted with PEG and then conjugated with AFN to be IR-AFN. Then, FA was conjugated onto the surface of IR-AFN to be IR-AFN-FA. At last, PTX was incorporated into IR-AFN-FA to fabricate a nanoplatform IR-AFN@PTX-FA. The NIR-II photothermal properties and pH/NIR-II triggered drug release were evaluated. The ability of IR-AFN@PTX-FA to target tumors was estimated using optical bioluminescence. In vitro and in vivo synergistic therapeutic effects of pH/NIR-II-triggered and tumor-targeted photothermal-chemotherapy were investigated in 4T1 tumor model.Results IR-AFN@PTX-FA showed excellent water solubility and physiological stability, which significantly enhanced the solubility of both IR1061 and PTX. After 5 min of laser irradiation at 1064 nm, IR-AFN@PTX-FA exhibited an effective photothermal effect compared with laser irradiation at 808 nm, even when blocked with 0.6 cm thick chicken breast. Cellular uptake experiments showed IR-AFN@PTX-FA utilized clathrin-mediated and caveolae-mediated endocytosis pathways to enter 4T1 cells, and was then delivered by the endosome to the lysosome. NIR-II laser irradiation and pH could synergistically trigger PTX release, inducing significant tumor inhibition in vitro and in vivo.Conclusion As a novel “all-in-one” nanoplatform, IR-AFN@PTX-FA was found to selectively target tumors and showed very efficient NIR-II photothermal effects and pH/NIR-II triggered drug release effects, showing a remarkable, synergistic photothermal-chemotherapy effect.
研究领域:
生物医学工程
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药学
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肿瘤学
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高影响因子
Polymers
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2017
·Vol. 9
·期 12
·698
·
IF 3.364
Yinglei Zhai,Xing Zhou,Lina Jia,Chao Ma,Ronghua Song,Yanhao Deng,Xueyao Hu,Wei Sun
The differences in micro-environment between cancer cells and the normal ones offer the possibility to develop stimuli-responsive drug-delivery systems for overcoming the drawbacks in the clinical use of anticancer drugs, such as paclitaxel, doxorubicin, and etc. Hence, we developed a novel endosomal pH-sensitive paclitaxel (PTX) prodrug micelles based on functionalized poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) diblock polymer with an acid-cleavable acetal (Ace) linkage (mPEG-PCL-Ace-PTX). The mPEG-PCL-Ace-PTX5with a high drug content of 23.5 wt % was self-assembled in phosphate buffer (pH 7.4, 10 mM) into nanosized micelles with an average diameter of 68.5 nm. The in vitro release studies demonstrated that mPEG-PCL-Ace-PTX5micelles was highly pH-sensitive, in which 16.8%, 32.8%, and 48.2% of parent free PTX was released from mPEG-PCL-Ace-PTX5micelles in 48 h at pH 7.4, 6.0, and 5.0, respectively. Thiazolyl Blue Tetrazolium Bromide (MTT) assays suggested that the pH-sensitive PTX prodrug micelles displayed higher therapeutic efficacy against MCF-7 cells compared with free PTX. Therefore, the PTX prodrug micelles with acetal bond may offer a promising strategy for cancer therapy.Keywords:prodrug;polymer micelles;pH-sensitive;acetal;paclitaxel
研究领域:
药学
·
肿瘤学
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DOI
PubMed
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
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2022
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IF 3.915
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.
研究领域:
药学
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癌症研究
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药物递送系统
·
生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
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2023
·
IF 2.9
Tian Yi Wu,Wen Jie Cao,Zi Ling Li,Yan Chun Gong,Xiang Yuan Xiong
Drugs with different solubility can be selectively embedded into polymersomes with the hydrophilic core and hydrophobic bilayer. Novel folate-targeted Pluronic/poly (D,L-lactide-b-glycolide) polymersomes were constructed and used for the co-delivery of paclitaxel (PTX) and doxorubicin (DOX) to improve their inhibitory effect over cancer cells. The particle size of blank polymersomes was mainly distributed below 125 nm. The release of PTX and DOX from polymersomes showed an initial burst release followed by a sustained and slow release. The in vitro cytotoxicity data showed that the targeted co-loaded polymersomes (PTX&DOX FA-Ps) exhibited better inhibitory effect than single-loaded polymersomes and free drugs did. Furthermore, PTX&DOX FA-Ps showed the synergistic therapeutic effect over OVCAR-3 cancer cells. The cellular uptake results also showed that folate modified polymersomes had excellent targeting performance. Therefore, the folate-targeted Pluronic/poly (D,L-lactide-b-glycolide) polymersomes have potential application value as novel drug carriers to co-deliver PTX and DOX.
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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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）