Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 37
·7768-7774
·
IF 4.543
Yuping Wei,Liang Zhang,Yankai Fu,Xia Xu
Paclitaxel (PTX) is widely used to treat ovarian, breast, lung, pancreatic, cervical and other cancers, however, the cell uptake and utilization of PTX is greatly limited by its slow penetration rate and poor solubility in water. Therefore, it is of great interest to develop an efficient method for PTX delivery to improve its cellular uptake and utilization. A novel cell penetrating peptide, RRRRRWW (R7), is developed to accelerate the translocation of PTX into HeLa cells in the organic solvent-free system to suppress tumor growth. There is no significant cytotoxicity induced by the peptide alone even after 24 h incubation at 1 mM at 37 °C for both cancer cells and normal cells. In contrast, 30 min treatment with the R7/PTX complex leads to a significant decrease in the cell viability. The intracellular PTX concentration of the R7/PTX complex group is 3 fold that of the free PTX group. The in vivo animal experiments show that the tumor is dramatically suppressed by a tail vein injection of the R7/PTX complex. This system provides a novel approach for the delivery of PTX into tumor cells to efficiently suppress tumor growth.
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RARE METALS
·
2024
·Vol. 44
·期 1
·417-429
·
IF 9.6
Wu Xiao-Xia,Zhang Ding-Hu,Ding Yi-Nan,Cao Fei,Li Yang,Yao Jun-Lie,Miao Xin-Yu,He Lu-Lu,Luo Jun,Li Jian-Wei,Lin Jie,Wu Ai-Guo,Zheng Jia-Ping
Recently, stimuli-responsive nanocarriers capable of precision drug release have garnered significant attention in the field of drug delivery. Here, an in-situ dynamic covalent self-assembled (DCS) strategy was utilized to develop a co-delivery system. This assembly was based on a thiol-disulfide-exchange reaction, producing disulfide macrocycles in an oxidizing aerial environment. These macrocycles encapsulated the anti-cancer drug (paclitaxel, PTX) on the surface of gold nanoparticles, which served as photothermal therapy agents during the self-assembly. In the DCS process, the kinetic control over the concentration of each building unit within the reaction system led to the formation of a stable co-delivery nanosystem with optimal drug-loading efficiency. Notably, the high glutathione (GSH) concentrations in tumor cells caused the disulfide macrocycles in nanostructures to break, resulting in drug release. The stimuli-responsive performances of the prepared nanosystems were determined by observing the molecular structures and drug release. The results revealed that the self-assembled nanosystem exhibited GSH-triggered drug release and good photothermal conversion capability under near-infrared light. Moreover, the in vitro and in vivo results revealed that conjugating the targeting molecule of cRGD with co-delivery nanosystem enhanced its biocompatibility, chemo-photothermal anti-cancer effect. Overall, our findings indicated that in-situ DCS strategy enhanced the control over drug loading during the construction of the co-delivery system, paving a way for the development of more functional carriers in nanomedicine. Graphical abstract
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2025
·
IF 5.9
Kan Li,Shengbin Gui,Ningning Wang,Xiao Li,Chunqin Zhao,Mingyu Liu,Zhen Zhang
Intravenously administered nanoparticles (NPs) often bind with plasma proteins, forming protein corona that prompt rapid systemic clearance, a primary challenge in nanomedicine. In this study, we developed a pH- and GSH-sensitive “stealth” nanodelivery system, PTX@NPs-aPD1-IL, for sequential drug release. By using a biocompatible choline-based ionic liquid (IL) as the coating for NPs, the interaction and adsorption of NPs with serum proteins were reduced, achieving targeted delivery to the lung organ and increasing drug accumulation. In the weakly acidic extracellular tumor microenvironment (pH 6.5), the anti-PD-1 antibody (aPD-1) was first released to block the PD-1/PD-L1 pathway and restore the immunocidal function of T cells. In the highly reductive intracellular environment of tumor cells, the disulfide bonds were cleaved, causing NPs to rupture and release paclitaxel (PTX). It induced tumor cell apoptosis and triggered immunogenic cell death (ICD), promoted dendritic cells (DCs) maturation and activated T cells for chemo-immunotherapy. In the mouse orthotopic lung cancer model, PTX@NPs-aPD1-IL exhibited superior efficacy to other treatment groups at the same dose. This was due to the significantly increase in the release of immune factors, including TNF-α and IFN-γ, and the promotion of CD8 + T cells recruitment, which induced a stronger immune response, and thus enhanced the anti-lung cancer effect. In summary, PTX@NPs-aPD1-IL provided a promising strategy for effective chemo-immunotherapy for lung cancer through sequential release profile.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-18
·
IF 12.6
Huang Haoyang,Liu Shaowei,Xu Ligeng,Liang Hengrui,Wu Zihao,Chen Tianfeng,Wang Jinlin,Liu Jun
Though prescribed as first-line drugs for esophageal squamous cell cancer (ESCC) therapy, the antitumor efficacy of Nab-Paclitaxel (Nab-PTX) is still unsatisfactory owing to the limitation on the dosage and therapy duration of Nab-PTX caused by adverse effects. Inspired by the very essential role of Selenoprotein N (SelN) in mediating the calcium homeostasis and the associated redox homeostasis in cells, herein, in this essay, we screened the inhibition effect of selenium-containing drugs in different forms on ESCC cell line. Investigation on KYSE-150 cells demonstrated that Nab-PTX in combination with low dosage of LNT-SeNPs may synergistically improve its antitumor efficacy on ESCC cells through promoting the cellular apoptosis. Proteomics analysis uncovered the core synergistic mechanism of LNT-SeNPs on Nab-PTX was significantly dependent on the endoplasmic reticulum (ER) stress induced by SelN-mediated Ca 2+ -IRE1α, IRE1α(S724)-CHOP-BCL2 axis. SelN knockdown KYSE-150 cell model further confirmed the very indispensable role of SelN in mediating the synergistic effect on Nab-PTX. Moreover, in vivo evaluation on KYSE-150 tumor-bearing mice models also demonstrated the supplementation of LNT-SeNPs with low dosage during the Nab-PTX treatment may synergize the antitumor efficacy and significantly mitigate the adverse reactions or toxicity resulting from a substantial dose of Nab-PTX. Overall, along with the facile accessibility of raw materials, this study reports LNT-SeNPs as a synergistic agent to promote the antitumor efficacy of Nab-PTX, which may be translated as a wide-applicable, efficient and highly safe strategy for clinical treatment of ESCC. Graphical abstract
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BIOMACROMOLECULES
·
2022
·
IF 6.978
Zixue Li,Wei Zhao,Na Liang,Pengfei Yan,Shaoping Sun
In this study, a tumor-targeting and pH-sensitive inclusion complex based on the host–guest recognition between the chitosan and folic acid grafted HP-β-CD (FA–CS–CD) and stearic acid modified 2-benzimidazolemethanol (BM-SA) was designed and fabricated for the controlled delivery of paclitaxel (PTX). Through the combination of computational simulations and experiments, the interaction between FA–CS–CD, BM-SA, and PTX was investigated, and the optimized preparation method was obtained. For the optimized PTX-loaded FA–CS–CD/BM-SA inclusion complex, the particle size and zeta potential were 146 nm and +15.4 mV, respectively. In vitro drug release study revealed the pH-triggered drug release behavior of the inclusion complex. Both in vitro and in vivo evaluations demonstrated that the PTX-loaded FA–CS–CD/BM-SA inclusion complex exhibited enhanced antitumor efficiency and minimized systemic toxicity. This system might be a promising carrier for PTX.
研究领域:
药剂学
·
分子生物学
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JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 23
·期 1
·763
·
IF 12.6
Qian Xueqian,Yuan Yi,Zhang Yaning,Li Manlin,Wang Xiaotong,Li Weikai,Wen Ling,Duan Guangxin,Han Yangyang
Background Ovarian cancer is one of the most prevalent gynecologic malignancies and ranks as a leading cause of death in female cancers. Chemotherapy remains the primary treatment modality, however, the development of chemoresistance poses a significant obstacle in ovarian cancer therapy, contributing to its high mortality rate. Results In this paper, we report a multifunctional nanoparticle that enables laser-controlled release of co-loaded paclitaxel (PTX) and STMN1 siRNA for synergistic combination therapy. This nanoparticle can improve the microtubule stability by interfering the expression of STMN1, thereby increasing the sensitivity to PTX, blocking cells in the G2/M phase, and ultimately leading to cancer cell death. Additionally, it exhibits enhanced bioavailability, reduced systemic toxicity, and photothermal properties suitable for in vivo imaging. Conclusions Our nanoparticle offers an innovative strategy for the concurrent therapy and monitoring of ovarian cancer, enhancing therapeutic efficacy and diagnostic precision. Graphical abstract
研究领域:
肿瘤学
·
纳米医学
·
药物递送
·
分子治疗
·
癌症生物学
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American Journal of Cancer Research
·
2025
·Vol. 15
·期 6
·2618
·
IF 2.9
Yixin Wang,Lang Jin,Chuanjie Zong,Xidong Zhang
Osteosarcoma is a prevalent primary malignant bone tumor in young adults and adolescents, characterized by a high recurrence rate despite advancements in chemotherapy and surgical methods. This study investigated the effects of integrating high-dose methotrexate with cisplatin and paclitaxel on survival outcomes in osteosarcoma patients, and to identify prognostic factors influencing these outcomes. A retrospective analysis was conducted on 208 osteosarcoma patients treated between January 2013 and December 2018. Patients were divided into two groups: standard chemotherapy group (SC, n = 104) and cisplatin + paclitaxel + high-dose methotrexate (CPM, n = 104). The primary endpoints were progression-free survival (PFS) and overall survival (OS), while secondary endpoints included efficacy assessments. Kaplan-Meier survival curves were used to assess survival distributions, and statistical analyses were performed using SPSS 29.0. The CPM group demonstrated significantly longer PFS (16.85 ± 3.40 months vs. 15.72 ± 3.21 months, P = 0.015) and higher 5-year OS rates (54.81% vs. 40.38%, P = 0.037) compared to the SC group. Completion of chemotherapy and a response rate greater than 90% were identified as strong positive prognostic indicators. In contrast, pathologic fractures at diagnosis, lung metastases, and elevated lactate dehydrogenase levels were associated with poorer outcomes. Multivariate analysis underscored chemotherapy response and treatment adherence as independent survival predictors. The combination of cisplatin and paclitaxel with high-dose methotrexate significantly improves PFS and OS compared to standard chemotherapy. Moreover, treatment completion and achieving a chemotherapy response greater than 90% are critical factors for favorable prognosis.
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2021
·Vol. 25
·期 8
·3744-3753
·
IF 5.31
Zhong-Sheng Xiao,Lei Zhao,Xiao-Ning Zhang,Han-Xian Li,Zhi-Hui Yin
It has been reported that rs67085638 in long non-coding RNAs (lncRNA)-CCAT1 was associated with the risk of tumorigenesis. Also, CCAT1 could affect chemoresistance of cancer cells to paclitaxel (PTX) via regulating miR-24-3p and FSCN1 expression. In this study, we aimed to investigate the effect of rs67085638 on the expression of CCAT1/miR-24-3p/FSCN1 and the response of colon cancer to the treatment of PTX. 48 colon cancer patients were recruited and grouped by their genotypes of rs67085638 polymorphism as a CC group (N = 28) and a CT group (N = 20). PCR analysis, IHC assay and Western blot, TUNEL assay and flow cytometry were conducted. LncRNA-CCAT1 and FSCN1 mRNA/protein were overexpressed, whereas miR-24-3p was down-regulated in the CT-genotyped patients and cells compared with those in the CC-genotyped patients and cells. The survival of colon cancer cells was decreased, whereas the apoptosis of colon cancer cells was increased by PTX treatment in a dose-dependent manner. MiR-24-3p was validated to target lncRNA-CCAT1 and FSCN1 mRNA, and the overexpression of CCAT1 could reduce the expression of miR-24-3p although elevating the expression of FSCN1. Knockdown of lncRNA-CCAT1 partly reversed the suppressed growth of CT-genotyped tumours. And the knockdown of lncRNA-CCAT1 partly reversed the dysregulation of lncRNA-CCAT1 and FSCN1 mRNA/protein in rs67085638-CT + NC shRNA mice. The findings of this study demonstrated that the presence of the minor allele of rs67085638 increased the expression of CCAT1 and accordingly enhanced the resistance to PTX. Down-regulation of CCAT1 significantly re-stored the sensitivity to PTX of colon cancer cells.
研究领域:
癌症生物学
·
分子生物学
·
遗传学
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ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Tianxu Fang,Jun Zhang,Tiantian Zuo,Guangyu Wu,Yingxin Xu,Yifan Yang,Jie Yang,Qi Shen
Extracellular matrix (ECM) accumulating in the tumor microenvironment (TME) is generated by tumor-associated fibroblasts. It can elevate interstitial fluid pressure and form dense barriers in tumor tissues. Consequently, nanocarriers are hindered from permeating into deeper tumor sites. Thus, the programmed drug-releasing nanoparticles, G(TM)PPSP, were developed for TME remodeling and breast cancer therapy. Gelatin nanoparticles were linked with platinum nanoparticles (PtNPs) to obtain G(TM)PPSP with a size of 214.0 ± 5.0 nm. Telmisartan (TM) was loaded in gelatin nanoparticles. Paclitaxel (PTX) was attached to PtNPs via a dual redox responsive diselenide bond. TM release was mediated by MMP-2 because of gelatin degradation in TME, and then intracellular PTX was released because of diselenide linkage fracture triggered by ROS or glutathione. ECM was depleted owing to TGF-β downregulation by TM and direct ablation by the photothermal effect of PtNPs. 4T1 tumor progression was inhibited by PTX chemotherapy, intracellular ROS scavenging of PtNPs, and photothermal therapy (PTT). The tumor spheroid penetration assay proved G(TM)PPSP could permeate into deep tumor regions when MMP-2 existed. In vivo antitumor experiments implied G(TM)PPSP with PTT could inhibit tumor growth effectively and remodel TME via ECM depletion and immunity activation, indicating the potential of G(TM)PPSP-based chemo-photothermal combination therapy for breast cancer treatment.
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PHYTOTHERAPY RESEARCH
·
2021
·Vol. 35
·期 11
·6228-6240
·
IF 5.882
Tiantian Qin,Jinzhu Zhao,Xiaojie Liu,Leilei Li,Xueyan Zhang,Xiaoli Shi,Yu Ke,Weihua Liu,Junfeng Huo,Yalong Dong,Yiwei Shen,Yanyu Li,Mingjing He,Shuhua Han,Linlin Li,Chengxue Pan,Cong Wang
Although paclitaxel is a promising frontline chemotherapy agent for various malignancies, the clinical applications have been restricted by side effects, drug resistance, and cancer metastasis. The combination of paclitaxel and other agents could be the promising strategies against malignant tumor, which enhances the antitumor effect through synergistic effects, reduces required drug concentrations, and also suppresses tumorigenesis in multiple ways. In this study, we found that luteolin, a natural flavonoid compound, combined with low-dose paclitaxel synergistically regulated the proliferation, migration, epithelial–mesenchymal transition (EMT), and apoptosis of esophageal cancer cells in vitro, as well as synergistically inhibited tumor growth without obvious toxicity in vivo. The molecular mechanism of inhibiting cell migration and EMT processes may be related to the inhibition of SIRT1, and the mechanism of apoptosis induction is associated with the reactive oxygen species (ROS)/c-Jun N-terminal kinase (JNK) pathway–mediated activation of mitochondrial apoptotic pathway.
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JOURNAL OF BIOMATERIALS APPLICATIONS
·
2019
·
IF 2.442
Yu Gao,Tao Liu,Xuan Liu,Chao Wu
Folic acid functionalized gelatin-coated mesoporous hollow carbon nanospheres (FGMCN) were synthesized and applied to enhance the antitumor curative effect of paclitaxel (PTX) for human liver cancer cell lines (SMMC-7721). PTX was loaded in FGMCN by the adsorption method and the PTX-loaded samples (PTX-FGMCN) had a drug content of 29.8 ± 1.06%. The PTX-FGMCN with a sustained release effect was characterized by X-ray diffraction and differential scanning calorimeter in order to analyze the PTX state in FGMCN. In vitro cell experiments showed that FMHSN improves the uptake of PTX and promotes apoptosis due to the nano-targeting effect of FMHSN. An in vivo tumor bearing experiment in mice indicated that the PTX-FGMCN significantly inhibited the growth of tumors. All of these results suggested that the PTX-FGMCN may be an effective anti-hepatoma drug in the future.
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PLANT AND CELL PHYSIOLOGY
·
2017
·Vol. 58
·期 11
·1878-1890
·
IF 4.76
Hao Juan,Guo Hong,Shi Xinai,Wang Ye,Wan Qinghua,Song Yao-Bin,Zhang Lei,Dong Ming,Shen Chenjia
Taxus species are well-known for paclitaxel, which exhibits antitumor activities and is used for treating various cancers. Although most Taxus species are widespread in many areas, few studies have characterized the variation in metabolism among different Taxus species. Using an integrated approach involving ‘tandem mass tag’ labeling and liquid chromatography–tandem mass spectrometry (HPLC–MS), proteomes of T. media and T. mairei were investigated and 4078 proteins were quantified. Screening and classification of differentially expressed proteins revealed many metabolism-associated proteins. In detail, four enzymes involved in the flavonoid biosynthesis pathway were predominantly expressed in T. mairei. Four enzymes associated with supplying precursors for paclitaxel biosynthesis and three cytochrome P450 taxoid oxygenases were preferentially expressed in T. media compared with T. mairei. Furthermore, variations in taxoid contents between T. media and T. mairei were determined using HPLC–MS analysis. Variations in flavonoid contents between T. media and T. mairei were determined by HPLC analysis. A number of differentially expressed proteins may provide an explanation for the variation in metabolisms of different Taxus species.
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