Science China-Chemistry
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2014
·Vol. 57
·期 4
·624-632
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IF 1.516
Zhang Yu,Xiao ChunSheng,Li MingQiang,Ding JianXun,Yang ChenGuang,Zhuang XiuLi,Chen XueSi
A series of well-defined amphiphilic linear-dendritic block copolymers (telodendrimers, MPEG- b -PAMAM-cholesterol) with 1,2,4 or 8 cholesteryl groups (named as P1 , P2 , P4 , P8 , respectively) were synthesized. Their chemical structures were characterized with 1 H NMR and mass spectrum (MALDI-TOF MS). The telodendrimers could self-assemble into micelles in aqueous solution, and encapsulate chemotherapeutic drug doxorubicin (DOX) and paclitaxel (PTX) for combination therapy. All the telodendrimers could encapsulate DOX with similar capability. However, their drug-loading capability of PTX is increased with the increasing number of cholesteryl groups. P8 exhibited much higher PTX loading efficiency than its counterparts. Thus, P8 was selected for further application of drug delivery in the paper. The drug-loading micellar nanoparticles (NPs) of P8 were spherical in shape and their diameters were less than 150 nm which were determined by dynamic light scattering measurements (DLS) and transmission electron microscope (TEM). In vitro drug release experiment demonstrated that P8 exhibited a controlled release manner for both DOX and PTX, and the two drugs were released simultaneously. In vitro cytotoxicity experiment further demonstrated that the co-delivery of DOX and PTX in P8 exhibited better anti-cancer efficiency than the delivery systems encapsulated with single drug (DOX or PTX). This indicates a synergistic effect. The co-delivery system showed potential in future anti-cancer treatment.
研究领域:
药学
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肿瘤学
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生物材料学
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2023
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IF 5.2
Hengjun Zhou,Chenyu Liu,Simiao Yu,Farishta Shafiq,Weihong Qiao
Despite paclitaxel (PTX) as the first-line anti-tumor drugs, the unsatisfactory low-solubility in water remained a barrier to clinical application. Thus, the present study aimed at enhancing the solubility of PTX. Accordingly, we designed the amphiphilic conjugates (HP) as the delivery system and prepared self-assembly nanoparticles by the conjugates. Hemolysis assays showed the good biocompatibility of the conjugates. Meanwhile, binding affinity between the conjugates and PTX was explored based on the critical aggregation concentration (cac). The biggest solubilization for the nanoparticles was 193.56-fold, which exhibited as the solubility of 48.39 μg/mL. Cellular uptake assays revealed the valid internalization of nanoparticles and the targetability. In addition, the nanoparticles arrested the mitosis and further apoptosis. Cytotoxicity and three-dimensional multicellular spheroid (3DMCS) assays proved the strong growth inhibition capacity and the superior penetration ability for the nanoparticles. These results suggested that the HP conjugate we synthesized could provide potential insights into the delivery system for hydrophobic drugs on the aspects of anti-tumor.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2023
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IF 5.8
Kun Yang,Yixin Dong,Xun Li,Fei Wang,Yu Zhang
The combination of phototherapy and chemotherapy has become attractive and effective cancer treatment. However, the accurate delivery of both chemo-phototherapy drugs to the target site as well as the development of high-efficient phototherapy and chemotherapy drugs remain major challenges. In this study, indocyanine green (ICG) and paclitaxel (PTX)-loaded aptamer ferritin (HAS1411-PTX-ICG) was developed as a biocompatible nanoplatform for combined chemo/photothermal/photodynamic (PTT/PDT) therapy that was safe and highly effective against tumors. HAS1411 was prepared by coupling aptamer AS1411 to the surface of human H chain ferritin (HFtn) by the carbon diimide method to further enhance the targeting of HFtn. Both ICG and PTX were effectively encapsulated in the HAS1411 by incubation at 60 ℃. Moreover, under near-infrared (NIR) light irradiation , HAS1411 enhanced the photothermal effect and cell internalization of ICG, as well as the production of reactive oxygen species in cancer cells. HAS1411-PTX-ICG displayed effective cytotoxicity and a significant tumor spheroids inhibitory effect owning to the improved internalization of PTX and ICG mediated by TfR1 and nucleolin dual receptors. Co-loaded PTX combined with ICG can produce chemo/PTT/PDT under near-infrared (NIR) light irradiation, enhancing the anti-tumor effect. The dual-targeting HAS1411 nanocarrier developed in this study can be a promising delivery system for cancer therapy and the fabricated HAS1411-PTX-ICG possesses potential application in chemo-phototherapy.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2023
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IF 5
Pingfu Huang,Hui Yan,Hao Wu,Lulu Liu,Wenmin Niu,Bo Zhai,Ziwei Hu,Jingjuan Li,Qianming Du,Yang Zhou
The co-amorphous (CAM) system has attracted widely attention for improving the solubility of poor water solubility drug and provide a formulation strategy for combination administration system. Paclitaxel (PTX) belongs to biopharmaceutics classification system (BCS) class Ⅳ drug, with the poor water solubility and membrane permeability. This study aimed to preparing the CAM system between PTX and curcumin (CUR) by rotary evaporation method. The solid-state characterization of CAM indicated that the PTX and CUR presented as amorphous state, compared with crystalline PTX and CUR, the amorphous system could improve the saturated solubility and dissolution with significantly difference, besides, the PTX absorption permeability increased after amorphization with CUR, and the rat pharmacokinetic study exhibited that the PTX-CUR had a high C max and AUC 0-∞ compared with crystalline CUR and PTX, Furthermore, the amorphous CUR and PTX exhibited the stronger anti-tumor efficacy in A549 cell model in vivo . In addition, PTX-CUR exhibited physical stability under the long-term storage condition. In conclusion, amorphization of PTX and CUR provided a promising mothed to improve the anti-tumor efficacy and oral bioavailability of PTX.
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International Journal of Nanomedicine
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2023
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IF 8
Xiaoling Wang,Jianqing Gao,Xumei Ouyang,Junbo Wang,Xiaoyi Sun,Yuanyuan Lv
Background Mesenchymal stem cells (MSCs) possess inherent tropism towards tumor cells, and so have attracted increased attention as targeted-therapy vehicles for glioma treatment.Purpose The objective of this study was to demonstrate the injection of MSCs loaded with paclitaxel (Ptx)-encapsulated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) for orthotopic glioma therapy in rats.Methods Ptx-PLGA NP-loaded MSC was obtained by incubating MSCs with Ptx-PLGA NPs. The drug transfer and cytotoxicity of Ptx-PLGA NP-loaded MSC against tumor cells were investigated in the transwell system. Biodistribution and antitumor activity was evaluated in the orthotopic glioma rats after contralateral injection.Results The optimal dose of MSC-loaded Ptx-PLGA NPs (1 pg/cell Ptx) had little effect on MSC-migration capacity, cell cycle, or multilineage-differentiation potential. Compared with Ptx-primed MSCs, Ptx-PLGA NP-primed MSCs had enhanced sustained Ptx release in the form of free Ptx and Ptx NPs. Ptx transfer from MSCs to glioma cells could induce tumor cell death in vitro. As for distribution in vivo, NP-loaded fluorescent MSCs were tracked throughout the tumor mass for 2 days after therapeutic injection. Survival was significantly longer after contralateral implantation of Ptx-PLGA NP-loaded MSCs than those injected with Ptx-primed MSCs or Ptx-PLGA NPs alone.Conclusion Based on timing and sufficient Ptx transfer from the MSCs to the tumor cells, Ptx-PLGA NP-loaded MSC is effective for glioma treatment. Incorporation of chemotherapeutic drug-loaded NPs into MSCs is a promising strategy for tumor-targeted therapy.
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CARBOHYDRATE POLYMERS
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2022
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IF 10.723
Yang Xu,Na Liang,Jiyang Liu,Xianfeng Gong,Pengfei Yan,Shaoping Sun
In this study, cetyl 4-formylbenzoate alkyl and 4-(2-hydroxyethoxy) benzophenonesalicylaldazide modified biotinylated chitosan (CS-BT-HBS-CB) featured with aggregation-induced emission (AIE) characteristic, active tumor-targeting ability and pH-responsive drug release property was designed and synthesized. The polymer was fabricated by introducing hydrophobic segment, tumor targeting ligand, acid-sensitive bond and AIE fluorophore to the backbone of chitosan. Due to its amphiphilicity, the polymer could self-assemble into micelles and encapsulate paclitaxel (PTX) to form PTX-loaded CS-BT-HBS-CB micelles. The mean size of the micelles was 167 nm, which was beneficial to the EPR effect . Moreover, with the help of above functional groups, the micelles exhibited excellent AIE effect, triggered drug release behavior by acidic condition, selective internalization by MCF-7 cells and excellent cellular imaging capability. In vivo studies revealed that the PTX-loaded CS-BT-HBS-CB micelles could enhance the antitumor efficacy with low systemic toxicity. This micellar system would be a potential candidate for cancer therapy and bioimaging.
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2021
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IF 4.384
Deqian Zhao,Chenlu Hu,Qiang Fu,Huixia Lv
Triple negative breast cancer (TNBC) is the most dangerous subtype of breast cancer accompanying by unfavorable prognosis due to lack of specific therapeutic targets. Paclitaxel (PTX) is the first-line chemotherapeutic drug for TNBC and niclosamide (NLM) was identified as an inhibitor for TNBC and breast cancer stem cells (BCSCs). Intratumoral drug delivery system was a hopeful alternative for chemotherapeutic drug administration due to its targeting efficiency with lower systemic toxicity. Herein, an injectable PTX nanocrystals (PTX-NCs) and NLM nanocrystals (NLM-NCs) co-loaded PLGA-PEG-PLGA thermosensitive hydrogel (PN NCs-Ts Gel) was designed for TNBC intratumoral treatment. The final formulation realized high drug loading and appropriate particle size. PN NCs-Ts Gel displayed sustained drug release for up to 8 days in vitro. In vitro antitumor tests observed synergetic effects of combined therapy in terms of inhibiting cell proliferation and migration, inducing apoptosis . In vivo combined therapy presented a tumor growth inhibition rate about 68.8% and desired safety. Moreover, tumors after PN NCs-Ts Gel intratumoral injection possessed the lowest ratio of BCSCs, exhibiting this formulation had good ability in suppressing BCSCs and therefore could possibly prevent TNBC recurrence and metastasis. These results suggested that PN NCs-Ts Gel could be a promising strategy for TNBC treatment.
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DRUG DELIVERY
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2021
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IF 6.419
Wenwen Shen,Shuke Ge,Xiaoyao Liu,Qi Yu,Xue Jiang,Qian Wu,YuChen Tian,Yu Gao,Ying Liu,Chao Wu
In this study, we prepared a folic acid-functionalized SMMC-7721 liver cancer cell membrane (CM)-encapsulated paclitaxel nanocrystals system (FCPN) for hepatoma treatment. Transmission electron microscopy (TEM) characterization showed that FCPN was irregular spherical shapes with a particle size larger than 200 nm and a coated thickness of approximately 20 nm. In an in vitro release experiment, FCPN indicated a slowly release effect of paclitaxel (PTX). Cell experiments demonstrated that FCPN was taken up by SMMC-7721 cells and significantly inhibited the proliferation of SMMC-7721 cells, which illustrated that FCPN had good targeting ability compared with PN and CPN. According to the results of in vivo animal experiments, FCPN significantly inhibited tumor growth. Tissue distribution experiments proved that FCPN could accumulate significantly in tumor tissues, which further explained why FCPN had good targeting ability. These results clearly suggested that folate-functionalized homotypic CM bionic nanosystems might represent a very valuable method for liver cancer treatment in the future.
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Materials Science & Engineering C-Materials for Biological Applications
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2021
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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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Journal of Biomedical Research
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2021
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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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Acta Pharmaceutica Sinica B
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2020
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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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MOLECULAR PHARMACEUTICS
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2020
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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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