INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2024
·
IF 5.3
Chenyu Cao,Yifei Li,Fangzhou Shi,Shanshan Jiang,Yutong Li,Leilei Yang,Xinyi Zhou,Yuqiong Gao,Feiyan Tang,Huan Li,Shulan Han,Zhuo Yu,Yifang Zou,Jianfeng Guo
Doxorubicin (DOX) is a chemotherapy drug used for hepatocellular carcinoma (HCC) treatment, but its effectiveness can be dramatically dampened by cancer cell chemoresistance. Signal transducer and activator of transcription 3 (STAT3) is implicated with drug resistance in a range of cancers (e.g., HCC), and the STAT3 inhibition can reverse the resistance of cancer cells to chemotherapeutic drugs. In the present study, a combination regimen to improve the efficiency of DOX was provided via the STAT3 blockade using plumbagin (PLB). A poly(lactic-co-glycolic acid) decorated by polyethylene glycol and aminoethyl anisamide was produced in the present study with the hope of generating the nanoparticles for co-delivery of DOX and PLB. The resulting co-formulation suppressed the STAT3 activity and achieved the synergistic chemotherapy, which led to tumor inhibition in the mice with subcutaneous DOX-resistant HCC, without causing any toxicity. The present study reveals the synergism of DOX and PLB, and demonstrates a promising combinatorial approach for treating HCC.
研究领域:
肿瘤学
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药理学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Coatings
·
2022
·Vol. 12
·期 4
·524
·
IF 3.236
Zheng Zhao,Shilu Chen,Yao Xiao,Maobin Xie,Wen Yu
After traditional osteosarcoma resection, recurrence of tumor is still a major clinical challenge. The combination of chemotherapy and photothermal therapy (PTT) has great potential in improving therapeutic effect. However, the studies using polydopamine (PDA) as photothermal transducing agent to improve the anti-cancer activity of curcumin (CM)-loaded poly (l-lactic acid) (PLLA) microparticles (PLLA/CM) have seldom been investigated. In this study, we reported the synthesis of PDA-coated PLLA/CM microparticles (PDA-PLLA/CM) prepared by PDA coating on the surface of the PLLA/CM microparticles fabricated by solution-enhanced dispersion by supercritical CO2(SEDS) for chemo-photothermal therapy of osteosarcoma. The average particle sizes of PLLA/CM and PDA-PLLA/CM microparticles with a spherical shape were (802.6 ± 8.0) nm and (942.5 ± 39.5) nm, respectively. PDA-PLLA/CM microparticles exhibited pH- and near-infrared (NIR)-responsive release behavior to promote CM release in the drug delivery system. Moreover, PDA-PLLA/CM microparticles displayed good photothermal conversion ability and photothermal stability attributed to PDA coating. Additionally, the results of in vitro anti-cancer experiment showed that 500 μg/mL PDA-PLLA/CM microparticles had good anti-cancer effect on MG-63 cells and no obvious toxicity to MC3T3-E1 cells. After incubation with PDA-PLLA/CM microparticles for 2 days, NIR irradiation treatment improved the anti-cancer activity of PDA-PLLA/CM microparticles obviously and reduced the cell viability of osteosarcoma from 47.4% to 20.6%. These results indicated that PDA-PLLA/CM microparticles possessed a synergetic chemo-photothermal therapy for osteosarcoma. Therefore, this study demonstrated that PDA-PLLA/CM microparticles may be an excellent drug delivery platform for chemo-photothermal therapy of tumors.Keywords:osteosarcoma therapy;microparticles;curcumin;synergetic chemo-photothermal therapy
研究领域:
药学
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生物医学工程
·
癌症研究
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产品关联
DOI
高影响因子
Nanoscale
·
2017
·Vol. 9
·期 8
·2755-2767
·
IF 7.367
Junhui Sui,Yani Cui,Hanxu Cai,Shaoquan Bian,Zhiyi Xu,Ling Zhou,Yong Sun,Jie Liang,Yujiang Fan,Xingdong Zhang
pH-Sensitive pullulan-doxorubicin conjugates encapsulating sorafenib (P-Dox/S) nanoparticles were developed as a synergistic combinatorial delivery system against murine breast carcinoma. The nanoparticles can encapsulate Dox and sorafenib with ultra-high loading capacity (65.34 wt%) through chemical conjugation and physical loading, whereas can remain stable under physiological conditions and gradually release Dox and sorafenib with the decreasing pH. These conjugates can be effectively internalized and clearly suppress 4T1 cell growth in vitro. Furthermore, research data of in vivo animal models revealed that the synergistic combinatorial P-Dox/S nanoparticles heavily accumulated in solid tumor tissue sites to maximize therapeutic efficacy; they also significantly inhibited solid tumor growth, even remarkably reduced solid tumor volume in comparison to the initial volume, and obviously diminished adverse effects. The anti-tumor therapeutic effect obviously outperformed the delivery of combinational chemotherapy of free drugs or single drug-loaded P-Dox nanoparticles at the same concentration. These promising results indicate the high-efficiency synergistic chemotherapeutic effects of these nanoparticles. Combinational chemotherapy using P-Dox/S nanoparticles has important potential in the clinical treatment of malignancy for overcoming drug resistance and heterogeneity.
研究领域:
药学
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肿瘤学
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生物材料科学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
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2022
·Vol. 27
·期 23
·8455
·
IF 4.927
Hongping Xu,Junhong Ling,Han Zhao,Xinyi Xu,Xiao-kun Ouyang,Xiaoyong Song
Chemotherapy is a common method for tumor treatment. However, the non-specific distribution of chemotherapeutic drugs causes the death of normal cells. Nanocarriers, particularly mesoporous carriers, can be modified to achieve targeted and controlled drug release. In this study, mesoporous polydopamine (MPDA) was used as a carrier for the antitumor drug doxorubicin (DOX). To enhance the release efficiency of DOX in the tumor microenvironment, which contains high concentrations of glutathione (GSH), we used N,N-bis(acryloyl)cysteamine as a cross-linking agent to encapsulate the surface of MPDA with fucoidan (FU), producing MPDA-DOX@FU-SS. MPDA-DOX@FU-SS was characterized via transmission electron microscopy, thermogravimetric analysis, and X-ray photoelectron spectroscopy (XPS), and its antitumor efficacy in vitro was investigated. The optimal conditions for the preparation of MPDA were identified as pH 12 and 20 °C, and the optimal MPDA-to-FU ratio was 2:1. The DOX release rate reached 47.77% in an in vitro solution containing 10 mM GSH at pH 5.2. When combined with photothermal therapy, MPDA-DOX@FU-SS significantly inhibited the growth of HCT-116 cells. In conclusion, MPDA-DOX@FU-SS may serve as a novel, highly effective tumor suppressor that can achieve targeted drug release in the tumor microenvironment.Keywords:mesoporous polydopamine;antitumor;nanomedicine;photothermal synergistic chemotherapy
研究领域:
药理学
·
生物材料学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
·
2023
·
IF 0
Yiqing Liu,Peiyong Guo,Xinhao Dong,Yina Xu,Dan Li,Hua Zheng,Jianhong Liao
Here, we combined reversible addition-fragmentation chain transfer (RAFT) polymerization and amide coupling reaction to develop a novel drug-polymer conjugate using poly(AMA- co -IMMA)-b-poly(OEGMA) (termed as PAIPO) as nanocarriers. In order to enhance cellular uptake and obtain subsequent endo/lysosomal escape capacity, the dual-drugs-conjugated prodrug was then coupled with 2,3-dimethylmaleimide (DA) moieties and implanted with imidazolyl groups, respectively. Paclitaxel (PTX) was conjugated to PAIPO via 3,3′-dithiodipropionic acid (DPA) to construct a GSH-responsive moiety, while doxorubicin (DOX) was conjugated to PAIPO via 4-formyl benzoic acid to construct a pH-responsive moiety, which synergistically enabled a synchronized and precise drug delivery. The micelles self-assembled from DOX/ [email protected] DA showed an ideal average diameter (163.2–178.3 nm), contributing to passive targeting by the EPR effect. Moreover, a switch of the surface Zeta potential of micelles from steady negatively charged (− 9.74 ± 0.54 mV) at pH 7.4 to positively charged (+ 6.33 ± 1.25 mV) at pH 6.5, facilitated the long blood circulation and cellular endocytosis of micelles, respectively. More importantly, in vitro studies confirmed that DA M(DOX n /PTX) exhibited a strong synergism against tumor cells, and under slightly acidic conditions (pH 6.5), the combination index (CI) values for DA M(DOX 1 /PTX) on HeLa and Skov-3 cells were estimated to be 0.47 and 0.49 (previous to be 0.50 and 0.56 at pH 7.4), respectively. And in vivo results showed effective tumor accumulation potential, remarkable biosafety, and biocompatibility. Combined, such synchronized delivery approach based on multi-responsive micelles might potentiate the efficacy of combination chemotherapy in clinical cancer treatment.
研究领域:
药物递送系统
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肿瘤学
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生物材料
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产品关联
DOI
PubMed
Frontiers in Bioengineering and Biotechnology
·
2021
·
IF 5.89
Xie Dengchao,Ma Panpan,Ding Xin,Yang Xiao,Duan Lian,Xiao Bo,Yi Shixiong
Colon cancer ranks as the third most common malignancy in the world. Combination chemotherapy, resorting to electrospun fibrous technology, has been considered as a promising strategy to exert synergistic effects in colon cancer treatment. Herein, we manufactured various pluronic F127 (PF127)-modified electrospun fibrous meshes with different weight ratios of camptothecin (CPT) and curcumin (CUR). The fluorescence characterization of the obtained PF127-CPT-meshes, PF127-CUR-meshes, and PF127-CPT/CUR-meshes (2:1) showed that CPT and CUR were evenly distributed within individual fibers of these meshes. Drug release experiments revealed that both types of drugs could be released from fibrous meshes simultaneously and sustainably. Importantly, these meshes exhibited strong in vitro anti-colon cancer activities, compared with the control meshes without drugs. Moreover, the combination index values of the PF127-CPT/CUR-meshes (CPT/CUR weight ratio = 5:1, 3:1, or 2:1) were <0.5 after incubation for respective 24 and 36 h, indicating the synergistic anti-colon cancer effects of CPT and CUR in fibrous meshes. Collectively, these results demonstrate that PF127-CPT/CUR-meshes can be developed as an efficient implantable system for effective synergistic treatment of colon cancer.
研究领域:
肿瘤学
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药剂学
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生物材料学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Huijiao Fu,Xiaoqiao Guo,Feng Fang,Cao Zhou,Yuanyuan Chen,Xuanbo Zhang,Bingchen Zhang,Xinran Li,Qiwen Liu,Jie Liu,Wei Chen,Ling Yu,Zhiqiang Yu,Xuefeng Wang
Cisplatin serves as the cornerstone medication in ovarian cancer (OC) chemotherapy; however, numerous resistance factors exist, resulting in unsatisfactory clinical treatment outcomes. Concurrently, OC frequently establishes an immunosuppressive microenvironment, which further exacerbates the challenges of cisplatin chemotherapy. Hence, it is particularly significant to explore a therapeutic approach capable of overcoming cisplatin resistance while reversing the immunosuppressive microenvironment of OC. Here, we synthesized a novel cisplatin polyprodrug (PTP) containing thioketal units, which self-assembled with a stimulator of interferon genes (STING) small-molecule agonist (SR-717) to form redox-smart-responsive PTP@SR-717 nanoparticles (NPs), enabling synergistic chemo-immunotherapy. Specifically, PTP@SR-717 NPs enhanced the anti-tumor effect of cisplatin through three key mechanisms: (i) Pre-target factors: Enhancing intracellular cisplatin uptake and reducing GSH-mediated detoxification to promote platinum accumulation. (ii) On-target factors: Utilizing molecular damage-associated molecular patterns (DAMPs) triggered by cisplatin to activate the STING pathway, thereby synergistically amplifying the STING-TBK1-IRF3 signaling and efficiently triggering an immune response. (iii) Post-target factors: Combining chemotherapy and immunotherapy to harness the immune system for tumor eradication. In conclusion, this study presents an effective approach to addressing the challenges associated with cisplatin in the clinical treatment of OC.
研究领域:
肿瘤学
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药理学
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免疫学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Zixu Liu,Wei Chu,Qianhe Sun,Linxuan Zhao,Xinyi Tan,Yu Zhang,Tian Yin,Haibing He,Jingxin Gou,Xing Tang
Combination, synergistic chemotherapy with gemcitabine (GEM) and cisplatin (CDDP) is a common strategy, and has been recommended for tumor treatment due to its promoted therapeutic effect and reduced systemic toxicity. However, this process involves the intravenous infusion of GEM prior to that of CDDP, which is inconvenient for patients and staff. Here, a novel hybrid nano-carrier system comprised of micelles encapsulated within PEGylated liposomes is proposed, in order to combine the unique strengths of each component. CDDP was bonded with PLG-PEG, and then the formed CDDP@PLG-PEG micelles and GEM were co-loaded inside PEGylated liposomes. The hybrid liposomes with the optimized GEM/CDDP ratio (1:0.6) showed a roughly spherical morphology, appropriate drug loading, and sustained release behavior. In vitro, the hybrid liposomes had 1.72-fold increased cellular uptake, and 57.42%-fold decreased IC 50 value. In vivo , pharmacokinetic studies showed increased t 1/2 values (125.64%- and 128.57%-folds for GEM and CDDP), decreased clearance (41.90%- and 2.37%-folds), and promoted AUC (262.76%- and 4577.24%-folds). Finally, an in vivo antitumor study showed effective activity in regards to lung tumor size and weight, which were 40.48%- and 33.11%-folds that of GEM/CDDP solution. In summary, we demonstrated the development of an effective micelle-containing PEGylated hybrid liposomes for combined GEM/CDDP delivery.
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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DOI
PubMed
高影响因子
Science China-Chemistry
·
2021
·Vol. 64
·期 6
·1020-1030
·
IF 9.445
Tu Yalan,Zheng Rui,Yu Fangzhou,Xiao Xuan,Jiang Maoling,Yuan Youyong
Determination of whether multidrug nanocarriers can deliver and release loaded drugs at a predefined synergistic ratio to target cancer cells is crucial. Although there are many successful applications for delivery of multiple drugs, most current carriers are unable to achieve coordinated loading and release, leading to a drug release ratio that disagrees with the predefined loading ratio. In this work, a simple dual-drug delivery system with a flexible and controllable drug release ratio was constructed to deliver two anticancer drugs, doxorubicin (DOX) and curcumin (CUR). The drug ratio of DOX and CUR can be easily tuned for an enhanced synergistic effect, and the drugs can be released at predesigned ratios due to synchronous drug activation and nanoparticle collapse. Drug release at predefined ratios for synergistic anticancer therapy was demonstrated via in vitro and in vivo experiments. Therefore, the dual drug delivery system developed here provides a simple and efficient strategy for combination chemotherapy.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
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产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Jingjing Chai,Jiawei Hu,Tao Wang,Xing Bao,Jiajie Luan,Yan Wang
There is an urgent need to develop efficient treatments for highly invasive triple-negative breast cancer (TNBC) with a high rate of postoperative. Baicalin (BA) has shown inhibitory effects on several tumor cells and could activate ferroptosis in some tumor cells by producing reactive oxygen species (ROS). For overcoming the shortcomings of BA in clinical applications and enhancing the effect of ferroptosis in TNBC, herein, a multifunctional liposome (BA-Fe(III) coordination-polymer-loaded liposome, BA-Fe(III) Lipo) was developed for synergistic chemotherapy of TNBC with ferroptosis activation. Fe(III) released from BA-Fe(III) Lipo could be efficiently reduced to Fe(II) in the presence of high glutathione in tumor microenvironment, which in turn catalyzed the oxidation of unsaturated fats through lipid peroxidation for more ROS production. In addition, BA-Fe(III) Lipo activated tumor cell ferroptosis by down-regulating the enzymatic activity of ferritin heavy chain 1 protein and glutathione peroxidase. This study provided a novel therapeutic strategy for the treatment of TNBC by ingeniously combining chemotherapy with the activation of ferroptosis, which presented potential clinical applications.
研究领域:
肿瘤学
·
药剂学
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生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2022
·
IF 9.965
Chunmei Lai,Bingchen Zhang,Dongmiao Li,Xiarong Tan,Bangyue Luo,Jiangwen Shen,Linyan Li,Jingwei Shao
Therapeutic modalities and drug formulations play a crucial and prominent role in actualizing effective treatment and radical cures of tumors. However, the therapeutic efficiency was severely limited by tumor recurrence and complex multi-step preparation of formulation. Therefore, the exploration of novel nanoparticles via a simple and green synthesis process for conquering traditional obstacles and improving therapeutic efficiency is an appealing, yet remarkably challenging task. Herein, a universal nanoplatform allows all cancerous cell-targeting, acid-responsive, cell imaging , synergistic chemotherapy, and nucleolar targeted phototherapy function was tactfully designed and constructed by using chemotherapeutic agents ursolic acid (UA), sorafenib (SF), and carbon dots (CDs) photosensitizers (PSs). The designed US NPs were formed by self-assembly of UA and SF associated with electrostatic , π-π stacking, and hydrophobic interactions. After hydrogen bonding reaction with CDs, the obtained (denoted as USC NPs) have a relatively uniform size of an average 125.6 nm, which facilitated the favorable accumulation of drugs at the tumor region through a potential enhanced permeability and retention (EPR) effect as compared to their counterpart of free CDs solution. Both in vitro and in vivo studies revealed that the advanced platform commenced synergistic anticancer therapeutic potency, imperceptible systematical toxicity, and remarkable reticence towards drug-resistant cancer cells. Moreover, the CDs PSs possess intrinsic nucleolus-targeting ability. Taken together, this theranostics system can fully play the role of “killing three birds with one stone” in a safe manner, implying a promising direction for exploring treatment strategies for cancer and endowing them with great potential for future translational research and providing a new vision for the advancing of an exceptionally forceful protocol for practical cancer therapy.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Sibei Wang,Fan Nie,Zhen Lin,Jing Xu,Yuanqiang Guo
Cancer poses a significant medical challenge worldwide. Research into tumor biology has revealed the prevalence of acidic conditions and abnormally high levels of reactive oxygen species (ROS) within the tumor microenvironment. In response to these findings, a ROS-responsive crosslinker, (((oxalylbis(oxy))bis(methylene))bis(4,1-phenylene))diboronic acid (OBA), was designed and synthesized using (4-hydroxymethyl)phenylboronic acid and ethanedioyl chloride as reactants. pH-responsive boronate ester bonds were formed between the diboronic acid groups of the crosslinker and the dihydroxyl groups of the naturally occurring active Astragalus polysaccharide (ASP). This resulted in the successful construction of pH/ROS dual-responsive nanogels (BAI@ASPOBA) loaded with the chemotherapeutic natural small molecule baicalein (BAI). Characterization of BAI@ASPOBA through molecular dynamics simulations and other methods demonstrated that it not only inhibited the proliferation of A549 tumor cells in vitro but also exhibited remarkable anti-tumor activity in vivo , along with excellent safety and biocompatibility. Further mechanistic studies revealed that the anti-tumor activity arises from the synergistic enhancement of the chemotherapeutic effects of BAI and the natural polysaccharide ASP. Specifically, the constructed BAI@ASPOBA nanogels enhanced the anti-tumor efficacy of BAI, while ASP, serving as the carrier for the nanomaterials, played an immunostimulatory role, facilitating tumor immunotherapy. The design and development of the novel BAI@ASPOBA nanogels in this study are anticipated to provide a new and effective treatment strategy for cancer therapy.
研究领域:
生物医学工程
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）