Applied Materials Today
·
2021
·
IF 10.041
Yu Chen,Yi Lu,Danrong Hu,Jinrong Peng,Yao Xiao,Ying Hao,Meng Pan,Liping Yuan,Zhiyong Qian
Colorectal cancer is the third most frequently diagnosed cancer in men and the second most frequent in women, with a mortality of approximately half the incidence. Currently, there is no specific consensus regarding standard treatments for colorectal cancer, and new and effective treatment regimens are yet to be developed. Cabazitaxel (CTX), a derivative of paclitaxel, has better anticancer activity than paclitaxel and docetaxel, and has low structural affinity with the MDR1 efflux pump, which offers the advantage of overcoming multidrug resistance. However, the adverse effects and poor stability impede its clinical applications; therefore, we synthesized a new block copolymer (MPEG 2k -PCL 10k ) to prepare CTX nanoparticle formulations to enhance its biocompatibility and bioavailability. Compared with the CTX preparation Jevtana®, the drug loading, stability and antitumor efficacy of the nanoparticles were significantly improved, while the cytoxicity was notably reduced. The results indicate that CTX-MPEG 2k -PCL 10k nanoparticle preparations have high security and excellent anti-tumor effects, and has great application potential in the colorectal cancer therapy.
研究领域:
肿瘤学
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药剂学
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生物医学工程
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产品关联
DOI
高影响因子
Advanced Science
·
2024
·Vol. 11
·期 33
·2404800
·
IF 14.3
Yu Chen,Liqun Dai,Kun Shi,Meng Pan,Liping Yuan,Zhiyong Qian
The treatment of colorectal cancer is always a major challenge in the field of cancer research. The number of estimated new cases of colorectal cancer worldwide in 2020 is 1 148 515, and the estimated number of deaths is 576 858, revealing that mortality accounted for approximately half of the disease incidence. The development of new drugs and strategies for colorectal cancer treatment is urgently needed. Thermosensitive injectable hydrogel PDLLA-PEG-PDLLA (PLEL) loaded with cabazitaxel (CTX) is used to explore its anti-tumor effect on mice with orthotopic colorectal cancer. CTX/PLEL is characterized by a solution state at room temperature and a hydrogel state at physiologic temperature. The excipients MPEG-PCL and PDLLA-PEG-PDLLA have good biocompatibility and biodegradability. The simple material synthesis and preparation process renders this system cost-effective and more conducive to clinical transformation. An orthotopic colorectal cancer model is established by transplantation subcutaneous tumors onto the cecum of mice. According to the results of experiments in vivo, CTX/PLEL significantly inhibits orthotopic colorectal cancer and liver metastasis in mice. The results indicate that CTX/PLEL nanoparticle preparations have high security and excellent anti-tumor effects, and have great application potential in colorectal cancer therapy.
研究领域:
肿瘤学
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药剂学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
·
2018
·Vol. 20
·期 2
·1-15
·
IF 2.127
Han Xiaoxiong,Gong Feirong,Sun Jing,Li Yueqi,Liu XiaoFei,Chen Dan,Liu Jianwen,Shen Yaling
Stimulus-responsive polymeric micelles (PMs) have recently received attention due to the controlled delivery of drug or gene for application in cancer diagnosis and treatment. In this work, novel glutathione-responsive PMs were prepared to encapsulate hydrophobic antineoplastic drug, cabazitaxel (CTX), to improve its solubility and toxicity. These CTX-loaded micelles core cross-linked by disulfide bonds (DCL-CTX micelles) were prepared by a novel copolymer, lipoic acid grafted mPEG-PLA. These micelles had regular spherical shape, homogeneous diameter of 18.97 ± 0.23 nm, and a narrow size distribution. The DCL-CTX micelles showed high encapsulation efficiency of 98.65 ± 1.77%, and the aqueous solubility of CTX was improved by a factor of 1:1200. In vitro release investigation showed that DCL-CTX micelles were stable in the medium without glutathione (GSH), whereas the micelles had burst CTX release in the medium with 10 mM GSH. Cell uptake results implied that DCL-CTX micelles were internalized into MCF-7 cells through clathrin-mediated endocytosis and released cargo more effectively than Jevtana (commercially available CTX) owing to GSH-stimulated degradation. In MTT assay against MCF-7 cells, these micelles inhibited tumor cell proliferation more effectively than Jevtana due to their GSH-responsive CTX release. All results revealed the potency of GSH-responsive DCL-CTX micelles for stable delivery in blood circulation and for intracellular GSH-trigged release of CTX. Therefore, DCL-CTX micelles show potential as safe and effective CTX delivery carriers and as a cancer chemotherapy formulation.
研究领域:
药学
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纳米医学
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肿瘤学
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产品关联
DOI
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 1
·262
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IF 5.4
Yuting Liu,Xinhui Wang,Zhe Wang,Rui Liao,Qian Qiu,Yuequan Wang,Cong Luo
Cabazitaxel (CTX) has distinct therapeutic merits for advanced and metastatic cancer. However, the present clinical formulation (Jevtana®) has several defects, especially for undesirable tumor-targeting and serious side effects, greatly limiting the therapeutic efficacy. Small-molecule prodrug-based nanoassemblies integrate the advantages of both prodrug strategy and nanotechnology, emerging as a promising treatment modality. Herein, disulfide bonds with different lengths were employed as linkages to elaborately synthesize three redox-sensitive stearyl alcohol (SAT)-CTX prodrug-based nanoassemblies (SAC NPs, SBC NPs and SGC NPs) for seeking optimal chemotherapeutical treatment. All the prodrug-based nanoassemblies exhibited impressive drug-loading efficiency, superior self-assembly capability and excellent colloidal stability. Interestingly, the drug release behaviors of three prodrug-nanoassemblies in the same reductive environment were different owing to tiny changes in the carbon chain length of disulfide bonds, resulting in disparate cytotoxicity effects, pharmacokinetic outcomes and in vivo antitumor efficacies. Among them, SAC NPs displayed rapid drug release, excellent cytotoxicity, long blood circulation and enhanced tumor accumulation, thus showing strong tumor inhibition in the 4T1-bearing mouse model. Our study shed light on the vital role of connecting bonds in designing high-efficiency, low-toxicity prodrug nanoassemblies.Keywords:cabazitaxel;disulfide bond;prodrug nanoassemblies;reduction-responsive;cancer therapy
研究领域:
药学
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Acupuncture and Herbal Medicine
·
2024
·Vol. 4
·期 1
·113
·
IF 0
Huang Dandan,Tang Zhongjie,Pu Xiao,Wang Tianqi,Gao Feiyan,Li Chong
Objective: In this study, we aim to enhance the anti-prostate cancer efficacy of cabazitaxel (CTX) and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1 (Rk1/CTX-Lip). Methods: Physical and chemical properties of Rk1/CTX-Lip were investigated. We evaluated the biological functions of Rk1/CTX-Lip, both in vitro and in vivo . A subcutaneous prostate cancer (RM-1)-bearing mouse model was established to study the efficacy of Rk1/CTX-Lip inhibition in tumors. Simultaneously, a Candida albicans infection model was established in tumor-bearing mice to study the infection-relieving efficacy of Rk1/CTX-Lip. Finally, biocompatibility and in vivo safety of Rk1/CTX-Lip were evaluated. Results: We successfully prepared Rk1/CTX-Lip, achieving high CTX encapsulation efficiency (97.24 ± 0.75)% and physical stability. Rk1/CTX-Lip demonstrated evasion of macrophage phagocytosis, effective tumor tissue targeting, and a significant reduction (>50%) in average tumor volume compared with Chol/CTX-Lip. Moreover, it relieved the concurrent infection burden and effectively regulated immune organs and cells, demonstrating superior biocompatibility. Conclusion: Rk1/CTX-Lip presents a promising new therapy for prostate cancer and holds potential for relieving concurrent fungal infections in cancer patients with low immunity. Export
研究领域:
药剂学
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肿瘤学
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免疫学
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微生物学
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DOI
NANOTECHNOLOGY
·
2018
·Vol. 30
·期 5
·055601
·
IF 3.404
Xiaoxiong Han,Feirong Gong,Lili Chi,Caochuan Feng,Jing Sun,Yiyang Chen,Jianwen Liu,Yaling Shen
Novel type of multifunctional polymeric micelles (PMs) designated as HM-PMss/CTX micelles were developed in the present study for tumor-targeted and glutathione (GSH)-responsive delivery of cabazitaxel (CTX). The surface of the vehicles was modified with piloting molecules (HM-3 peptide), which targets αvβ3 integrin overexpressed on cancer cells, and the micelle core was cross-linked by GSH-disintegrable disulfide linkages for controlled drug release. HM-PMss/CTX micelles were prepared using a mixture of two functionalized amphiphilic block copolymers and found to physically encapsulate CTX with excellent entrapment efficiency (93.94 ± 4.19%), drug-loading capacity (8.39 ± 2.28%), and a narrow size distribution. In vitro release profiles showed that CTX remained stably entrapped in the micelles in a release medium without GSH or with GSH of low concentration, while undergoing a rapid release in a highly reductive environment. Cellular uptake experiments showed that the conjugation of the targeting peptide, containing an arginine-glycine-aspartate sequence, enhanced the cellular uptake of HM-PMss/CTX micelles via αvβ3 integrin-mediated endocytosis. In vitro cell viability measurements revealed that blank micelles were biocompatible, while HM-PMss/CTX micelles, owing to their tumor-targeting ability and GSH sensitivity, effectively inhibited the proliferation of MDA-MB-231 breast cancer cells. These results indicate that HM-PMss/CTX micelles could be a promising platform for future intelligent drug delivery in cancer therapy.
研究领域:
药剂学
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肿瘤学
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生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Nano
·
2024
·
IF 8.2
Baoyue Zhang,Jiang Yu,Ruiping Huang,Jianying Ye,Fanlin Meng,Zhaochu Xu,Wenwen Cui,Jia Song,Siqi Wang,Yanjun Du,Qingzhi Lv,Wanling Zhu,Dan Liu,Yongjun Wang
Liposomes, particularly those designed for remote drug loading, have achieved remarkable success as drug-delivery vehicles in clinical settings. However, the lack of ionizable or coordinative groups prevents many promising drugs from being remotely loaded into liposomes for cancer therapy. Herein, to provide a universal remote loading approach, we chose cabazitaxel (CTX) as a model drug to modify galloyl group bridged by different lengths of alkyl chain. Fortunately, all the synthesized prodrugs could be actively loaded into liposomes via Fe 3+ gradient with high encapsulation efficiency and loading capacity. As the intraliposomal aqueous phase, Fe 3+ was not only served as the driving force of prodrugs remote loading, but also regarded as an exogenous replenishment to strengthen iron-dependent ferroptosis for multimodal therapy. The length of linkage between CTX and galloyl group played a crucial role in the chemical stability of prodrugs, in vitro drug release rate and in vivo pharmacokinetics behavior of prodrug liposomes. Among three prodrug liposomes, only decylene glycol-bridged CTX-gallic acid (CTX-DC-GA) liposomes kept a good balance between drug leakage during circulation and specific drug release under tumor microenvironment. Ultimately, CTX-DC-GA liposomes displayed optimal antitumor efficacy with good safety. We proposed Fe 3+ -based galloylated prodrug liposomes give new horizons for achieving the combination of ferroptosis and chemotherapy.
研究领域:
药剂学
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肿瘤学
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生物化学
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产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
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IF 10.8
Hezhen Xu,Shiyi Zuo,Danping Wang,Yu Zhang,Wenxiao Li,Lingxiao Li,Tian Liu,Yuanhao Yu,Qingzhi Lv,Zhonggui He,Jin Sun,Bingjun Sun
The clinical application of cabazitaxel (CTX) is restricted by severe dose-related toxicity, failing to considering therapeutic efficacy and safety together. Self-assembled prodrugs promote new drug delivery paradigms as they can self-deliver and self-formulate. However, the current studies mainly focused on the use of straight chains to construct self-assembled prodrugs, and the role of branched chains in prodrug nanoassemblies remains to be clarified. In this study, we systematically explored the structure–function relationship of prodrug nanoassemblies using four CTX prodrugs that contained branched chain aliphatic alcohols (BAs) with different alkyl lengths. Overall, CTX-SS-BA 20 NPs with the proper alkyl length exhibited significant improvements in both antitumor efficacy and biosafety. Furthermore, compared with straight chain (SC) modified prodrug nanoassemblies (CTX-SS-SC 20 NPs), CTX-SS-BA 20 NPs still hold great therapeutic promise due to its good biosafety. These findings illustrated the significance of BAs as modified chains in designing prodrug nanoassemblies for narrowing the efficacy-to-safety gap of cancer therapy.
研究领域:
药学
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纳米技术
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2026
·Vol. 16
·期 12
·6843
·
IF 14.9
Li Yang,Tingchao Liu,Meng Huo,Weiping Jia,Yu Chen,Maoxu Ge,Yan Pan,Jianfei Shi,Xiaohai Li,Si Wang,Yikang Shi
Background High expression of prostate-specific membrane antigen (PSMA) is observed in advanced prostate cancer, supplying a promising target for precision therapeutic interventions. Despite its efficacy in metastatic castration-resistant disease, cabazitaxel (CTX) is limited by severe systemic toxicity and a narrow therapeutic index, underscoring the urgent demand for tumor-selective delivery systems. Methods A novel PSMA-targeted dextran-based conjugate, Dextran-CTX-GLA-EuK, was synthesized via click chemistry by conjugating CTX, γ-linolenic acid (GLA), and a Glu-urea-Lys (EuK) PSMA-targeting ligand to bifunctionalized dextran. Critical in vitro and in vivo PSMA blocking experiments (using the PSMA inhibitor 2-PMPA) were performed to validate its targeting specificity. A thorough myelosuppression study was performed in murine models to evaluate the systemic hematological safety profile. The biodistribution profile and in vivo antitumor efficacy of the conjugate were evaluated in murine xenograft models. Results The conjugate Dextran-CTX-GLA-EuK exhibited favorable physicochemical properties, high water solubility, and strong PSMA-binding affinity. In vitro and in vivo PSMA blocking experiments conclusively verifying its PSMA-mediated specific cellular internalization and tumor accumulation. In PSMA-overexpressing xenograft models, the conjugate demonstrated selective tumor enrichment, with intratumoral CTX levels up to 98.3-fold higher than those of parent CTX, while reducing exposure in normal tissues. Dextran-CTX-GLA-EuK exerted prominent dose-dependent tumor growth inhibition, attaining a 96.6% suppression rate at a 10 mg/kg dosage in PC-3/PSMA tumors and prolonging the survival of 22Rv1 tumor-bearing mice. Importantly, comprehensive myelosuppression assays revealed that the conjugate only induced a transient reduction in white blood cell and neutrophil counts (which rapidly recovered to baseline) without impairing bone marrow hematopoietic function; unlike CTX, the conjugate did not cause significant weight loss, organ toxicity, or hematological abnormalities in tumor-bearing mice. Conclusions These findings demonstrate that Dextran-CTX-GLA-EuK synergizes active targeting with dextran-based delivery, enhancing antitumor efficacy while abolishing dose-limiting toxicities. This strategy offers a clinically translatable approach for PSMA-directed therapy in prostate cancer.
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DOI
PubMed
高影响因子
BIOCONJUGATE CHEMISTRY
·
2016
·
IF 4.5
Peng Xue,Dan Liu,Jing Wang,Na Zhang,Jiahua Zhou,Lin Li,Weiling Guo,Mengchi Sun,Xiangfei Han,Yongjun Wang
Citronellol-cabazitaxel (CIT-ss-CTX) conjugate self-assembled nanoparticles (CSNPs) were designed and prepared by conjugating cabazitaxel with citronellol via the disulfide bond that is redox-sensitive to the high concentration of glutathione within tumor cells. Notably, the CSNPs maintained in the cell cytotoxicity. Moreover, the AUC0-t of CSNPs was 6.5-fold higher than that of cabazitaxel solutions and the t1/2 was prolonged 2.3 times. Furthermore, we found that CSNPs could be employed as an efficient carrier for other hydrophobic drugs or imaging agents. Thus, the in vivo targeting study was implemented via using 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR)-loaded CSNPs as imaging agent, which showed CSNPs could effectively accumulate at the tumor site. Curcumin, a hydrophobic anticancer drug, was successfully loaded in CSNPs which exhibits good stability and synergistic antitumor effects. The citronellol–cabazitaxel conjugate therefore has a promising perspective as a multifunctional nanomedicine for combination therapy and theranostics attributed to its long-circulation property, redox-sensitive mechanism, and high drug coloading capability.
研究领域:
药学
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纳米技术
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肿瘤学
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药物递送系统
·
诊疗一体化
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2025
·
IF 5.4
Yuanli Yang,Chenqian Feng,Xiaoling Li,Min Mu,Hui Li,Bo Chen,Rangrang Fan,Haifeng Chen,Gang Guo
Biomaterial-based modulation of the microenvironment represents a promising neuroprotective strategy for spinal cord injury (SCI). We first fabricated hyaluronic acid (HA)-graft-epigallocatechin gallate (EGCG) nanoparticles (HEN). These nanoparticles can synergistically exert anti-inflammatory and antioxidant effects, while HA can modulate the immune microenvironment. To further enhance therapeutic efficacy, Cabazitaxel (Cab) was incorporated into HEN to generate multifunctional Cabazitaxel-loaded HA-EGCG nanoparticles (Cab-HEN), which inhibited scar formation and modulated microtubule homeostasis, thereby promoting the beneficial regeneration of nerve axons in a rat SCI model. Through in situ injection at the T9 injury site, Cab-HEN significantly downregulated the expression of inflammatory factors, effectively mitigated oxidative damage induced by excessive reactive oxygen species (ROS), and reduced fibrin deposition and scar formation. Furthermore, Cab-HEN regulated microtubules and enhanced the regeneration of nerve fibers. Evaluations based on electrophysiological assessments, Basso, Beattie, and Bresnahan (BBB) scores, and bladder function recovery revealed the nanoparticles’ remarkable therapeutic efficacy in SCI. Therefore, biomaterials can facilitate axonal regeneration, tissue remodeling, and functional restoration following injury.
研究领域:
纳米医学
·
神经科学
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生物材料
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再生医学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2016
·
IF 1.733
Xiaoxiong Han,Dan Chen,Jing Sun,Jinsong Zhou,Duan Li,Feirong Gong,Yaling Shen
Cabazitaxel (CTX) is a second-generation semisynthetic taxane that demonstrates antitumor activity superior to docetaxel. However, the low aqueous solubility of CTX has hampered its use as a therapeutic agent. In this work, CTX-loaded N-t-butoxycarbonyl-L-phenylalanine end-capped monomethyl poly (ethylene glycol)-block-poly (D,L-lactide) (mPEG-PLA-Phe(Boc)/CTX) micelles were prepared to improve the solubility of CTX while retaining its superior stability before accessing the tumor site. The mPEG-PLA-Phe(Boc)/CTX micelles showed excellent stability in vitro compared with mPEG-PLA/CTX micelles. When stored at 25 °C, the mPEG-PLA/CTX micelles tended to aggregate within 1 h, whereas the mPEG-PLA-Phe(Boc)/CTX micelles were uniformly transparent even after three weeks. Dilution of mPEG-PLA/CTX micelles widened their size distribution and decreased the encapsulation efficiency, while significant change was not found in mPEG-PLA-Phe(Boc)/CTX micelles, even when diluted 1000-fold. Pharmacokinetic results in Sprague–Dawley rats indicated that, compared with Jevtana®, intravenous administration of mPEG-PLA-Phe(Boc)/CTX micelles stably retained the CTX in plasma with 26.03-fold larger of the area under the time–concentration curve, 2.13-fold longer of the half-life, and 9.99-fold higher of the maximum concentration. In conclusion, mPEG-PLA-Phe(Boc) micelle may be a potential nanocarrier not only to improve the solubility of CTX but also to prolong the blood circulation time, which results in improved biological activity.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）