Pharmaceutics
·
2025
·Vol. 17
·期 3
·316
·
IF 5.5
Yang Chen,Shuang Liang,Binglin Chen,Fei Jiao,Xuliang Deng,Xinyu Liu
Background/Objectives : Paclitaxel (PTX) is a potent anticancer drug that is poorly soluble in water. To enhance its delivery efficiency in aqueous environments, amphiphilic polymer micelles are often used as nanocarriers for PTX in clinical settings. However, the hydrophilic polymer segments on the surface of these micelles may possess potential immunogenicity, posing risks in clinical applications. To address this issue, nanomicelles based on human serum albumin (HSA)–hydrophobic polymer conjugates constructed via site-specific in situ polymerization-induced self-assembly (SI-PISA) are considered a promising alternative. The HSA shell not only ensures good biocompatibility but also enhances cellular uptake because of endogenous albumin trafficking pathways. Moreover, compared to traditional methods of creating protein–hydrophobic polymer conjugates, SI-PISA demonstrates higher reaction efficiency and better preservation of protein functionality. Methods : We synthesized HSA-PMEMA nanomicelles via SI-PISA using HSA and methoxyethyl methacrylate (MEMA)—a novel hydrophobic monomer with a well-defined and stable chemical structure. The protein activity and the PTX intracellular delivery efficiency of HSA-PMEMA nanomicelles were evaluated. Results : The CD spectra of HSA and HSA-PMEMA exhibited similar shapes, and the relative esterase-like activity of HSA-PMEMA was 94% that of unmodified HSA. Flow cytometry results showed that Cy7 fluorescence intensity in cells treated with HSA-PMEMA-Cy7 was approximately 1.35 times that in cells treated with HSA-Cy7; meanwhile, HPLC results indicated that, under the same conditions, the PTX loading per unit protein mass on HSA-PMEMA was approximately 1.43 times that of HSA. These collectively contributed to a 1.78-fold overall PTX intracellular delivery efficiency of HSA-PMEMA compared to that of HSA. Conclusions : In comparison with HSA, HSA-PMEMA nanomicelles exhibit improved cellular uptake and higher loading efficiency for PTX, effectively promoting the intracellular delivery of PTX. Tremendous potential lies in these micelles for developing safer and more efficient next-generation PTX formulations for tumor treatment.
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高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2017
·
IF 2.714
Jie Yang,Le Yun,Guowei Zhao,Feng Zhang,Yashao Chen,Changhao Wang
A pH-responsive surfactant system has been self-assembled between a cationic gemini surfactant hexamethylene-1,6-bis(dodecyldimethylammonium bromide) (12-6-12) and sodium octanedioate (C 8 Na 2 ), which was characterized by surface tension, proton nuclear magnetic resonance ( 1 H NMR), dynamic light scattering (DLS), transmission electronic microscopy (TEM) and fluorescence probe spectroscopy. The interaction between 12 and 6–12 and C 8 Na 2 are based on the electrostatic and hydrophobic interaction as evidenced by surface tension and 1 H NMR. The self-assembled 12-6-12/C 8 Na 2 system has been demonstrated to be concentration dependence and pH dependence. With increasing the concentration of C 8 Na 2 , the vesicle form of 12-6-12 can transform to micelles. Vesicle-to-micelle transition of the 12-6-12/C 8 Na 2 aggregates is reversible with tuning the pH values. The micropolarity inside the 12-6-12/C 8 Na 2 aggregates was characterized by fluorescence spectroscopy using pyrene as probe, indicating that the micropolarity is enhanced with the increased pH. Furthermore, the release assay of an oil-soluble drug paclitaxel performs well in this pH-responsive surfactant system and the drug releasing rate could be controlled by pH values.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Huiwen Hou,Yan Li,Wen Tang,Didi Gao,Zengmei Liu,Feiyan Zhao,Xinqing Gao,Peixue Ling,Fengshan Wang,Feng Sun,Haining Tan
Blocking the tumor nutrient supply through angiogenic inhibitors is an effective treatment approach for malignant tumors. However, using angiogenic inhibitors alone may not be enough to achieve a significant tumor response. Therefore, we recently designed a universal drug delivery system combining chemotherapy and anti-angiogenic therapy to target tumor cells while minimizing drug-related side effects. This system (termed as PCCE) is composed of biomaterial chondroitin sulfate (CS), the anti-angiogenic peptide ES2, and paclitaxel (PTX), which collectively enhance antitumor properties. Interestingly, the PCCE system is conferred exceptional cell membrane permeability due to inherent characteristics of CS, including CD44 receptor-mediated endocytosis. The PCCE could respond to the acidic and high glutathione conditions, thereby releasing PTX and ES2. PCCE could effectively inhibit the proliferation, migration, and invasion of tumor cells and cause apoptosis, while PCCE can affect the endothelial cells tube formation and exert anti-angiogenic function. Consistently, more potent in vivo antitumor efficacy and non-toxic sides were demonstrated in B16F10 xenograft mouse models. PCCE can achieve excellent antitumor activity via modulating angiogenic and apoptosis-related factors. In summary, we have successfully developed an intelligent and responsive CS-based nanocarrier known as PCCE for delivering various antitumor drugs, offering a promising strategy for treating malignant tumors.
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MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Huiling Li,Li Tian,Shuning Yang,Chao Li,Yujia Song,Ruidan Li,Yanjia Guo,Juan Lu
A signal-on solid-state electrochemiluminescence (ECL) sensor based on luminol@carbon nanotubes (luminol@CNTs) and CdTe-ZnS@hydroxyapatite (CdTe-ZnS@HAP) was constructed for the detection of paclitaxel (PTX). In this sensing platform, luminol was used as the main luminophore and CdTe-ZnS was used as a co-reaction accelerator. CNTs and HAP were acted as carriers to adsorb more luminophores and co-reaction promoters. In addition, due to the enhanced effect of PTX on the ECL intensity of the luminol-O 2 system, PTX was introduced as the final detection target. Under the optimal experimental conditions, the ECL intensity change values (ΔI) of the sensor showed a good linear relationship with the logarithm of PTX concentration in the range of 3 × 10 -12 − 3 × 10 -7 molL -1 , and the limit of detection was 1 × 10 -12 mol L -1 (S/N = 3). This method was successfully applied to the determination of trace PTX concentration in serum.
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Advanced Science
·
2024
·
IF 14.3
Haisi Wu,Xianbao Sun,Kaiming Li,Jinyu Li,Hui Jiang,Dan Yan,Ya Lin,Yan Ding,Yawen Lu,Xiaole Zhu,Xufeng Chen,Xiaolin Li,Gaolin Liang,Huae Xu
Paclitaxel (PTX) is a first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC) but it can induce indoleamine 2,3-dioxygenase (IDO) activation, which severely lowers down its immuno-chemotherapeutic effect. To address this issue, a smart peptide hydrogelator Nap–Phe–Phe–Phe–Lys–Ser–Thr–Gly–Gly–Lys–Ala–Pro–Arg–OH ( Nap-T ), which co-assembles with PTX and an IDO inhibitor GDC0919 to form a hydrogel GP@Gel Nap-T, is rationally designed. Upon specific phosphorylation by pyruvate kinase M2 (PKM2), an overexpressed biomarker of NSCLC, Nap-T is gradually converted to Nap–Phe–Phe–Phe–Lys–Ser–Thr(H 2 PO 3 )–Gly–Gly–Lys–Ala–Pro–Arg–OH ( Nap-Tp ), leading to dehydrogelation and sustained release of PTX and GDC0919 within NSCLC tissues. The released PTX exerts chemotherapy on NSCLC cells as well as immunogenic cell death induction, while GDC0919 promotes the immuno-chemotherapeutic effect of PTX through IDO inhibition. We find that GP@Gel Nap-T enhances the infiltration of tumor-infiltrating immune cells and reduces the number of immunosuppressive cells in either tumor tissues or tumor-draining lymph nodes, thus enhancing the immuno-chemotherapy of PTX toward NSCLC. With this PKM2-responsive drug release strategy, the smart peptide hydrogel platform might be applied for NSCLC treatment in clinic in near future.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2025
·
IF 5.4
Xiaotong Zhang,Siying Yang,Tingting Mo,Yingshi Zhou,Haoyu Xue,Jinying Yuan,Lei Tao,Mei Tian,Yen Wei,Zengfang Huang
Aggregation-induced emission (AIE) materials can emit fluorescence with higher photoluminescence efficiency when aggregated or in the solid state, making them widely used in many fields recently. In this study, several novel N-substituted phenothiazine (PhT) derivatives HPMAD (HPMAC, HPMAN, HPMAP) with D-A structure were prepared by chemoenzymatic transesterification , Vilsmeier-Haack reaction and Knoevenagel condensation reaction , etc. Subsequently, the effects of functional groups with different natures on the optical properties of fluorescent molecules were investigated in detail. As compared with FPMA with an emission wavelength at 543 nm, the emission wavelengths of HPMAC, HPMAN and HPMAP were significantly red-shifted with the increase of electron-withdrawing and conjugation degree, and their maximum emission wavelengths were respectively at 595 nm, 599 nm and 649 nm. The quantum calculations also indicated that energy band gaps ΔE of HPMAC, HPMAN and HPMAP were obviously lower than that of the substrate FPMA, among which HPMAP had low ΔE of 3.04 eV due to the conjugation structure. Afterwards, amphiphilic copolymers PEG-HCC1, PEG-HCC2 and PEG-HCN were prepared by RAFT polymerization using PEGMA , HPMAC and HPMAN as monomers with different molar ratios, and their molar ratios in the copolymers were respectively about 23.7 %, 31.4 % and 30.8 %. Among them, PEG-HCN copolymers were easily dispersed in H 2 O solutions through self-assembly with a diameter of 100–200 nm, and exhibit significant aggregation-induced emission enhancement (AEE) phenomenon. Moreover, PEG-HCN FONs had excellent biocompatibility , lower toxicity, and good cellular endocytosis, which can be further used as a carrier for the anticancer drug of paclitaxel (PTX). Thus, drugs-carrying nanoparticles HCN-PTX FONs were constructed for drugs release and simultaneous imaging to track intracellular drug delivery , which demonstrates the potential for development in bioimaging, drugs delivery and medical diagnostics.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2014
·
IF 3.785
Qian Li,Shixian Lv,Zhaohui Tang,Muhua Liu,Dawei Zhang,Yan Yang,Xuesi Chen
Herein, we develop a co-delivery system of paclitaxel (PTX) and doxorubicin hydrochloride (DOX·HCl) based on methoxypoly(ethylene glycol)- block -poly( l -glutamic acid) (mPEG- b -PLG) for cancer treatment. PTX was grafted to the mPEG- b -PLG by esterification to give mPEG- b -PLG- g -PTX. DOX·HCl was encapsulated via electrostatic interaction and hydrophobic stack between the DOX·HCl and mPEG- b -PLG- g -PTX in aqueous solution. The release rate of DOX·HCl from the drug-loaded nanoparticles (mPEG- b -PLG- g -PTX-DOX) was slow at blood pH (pH 7.4), but obviously increased at endosome pH (pH 5.4). The mPEG- b -PLG- g -PTX-DOX exhibited slight synergistic effect in inhibition of proliferation of A549 and MCF-7 human cancer cells. For in vivo treatment of xenograft human breast tumor (MCF-7), the mPEG- b -PLG- g -PTX-DOX nanoparticles exhibited remarkable tumor inhibition effect with a 95.5% tumor-suppression-rate which was significantly higher than those of related single anticancer agents such as free DOX·HCl and mPEG- b -PLG- g -PTX. These results indicated that the mPEG- b -PLG- g -PTX-DOX would have great potential in cancer therapy.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
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高影响因子
BIOMATERIALS
·
2011
·
IF 7.883
Feihu Wang,Dianrui Zhang,Qiang Zhang,Yuxuan Chen,Dandan Zheng,Leilei Hao,Cunxian Duan,Lejiao Jia,Guangpu Liu,Yue Liu
Multidrug resistance (MDR) in tumor cells is a significant obstacle for successful cancer chemotherapy. Overexpression of drug efflux transporters such as P-glycoprotein (P-gp) is a key factor contributing to the development of tumor drug resistance. Verapamil (VRP), a P-gp inhibitor, has been reported to be able to reverse completely the resistance caused by P-gp. For optimal synergy, the drug and inhibitor combination may need to be temporally colocalized in the tumor cells. Herein, we investigated the effectiveness of simultaneous and targeted delivery of anticancer drug, paclitaxel (PTX), along with VRP, using DOMC-FA micelles to overcome tumor drug resistance. The floate-functionalized dual agent loaded micelles resulted in the similar cytotoxicity to PTX-loaded micelles/free VRP combination and co-administration of two single-agent loaded micelles, which was higher than that of PTX-loaded micelles. Enhanced therapeutic efficacy of dual agent micelles could be ascribe to increased accumulation of PTX in drug-resistant tumor cells. We suggest that the synergistic effect of folate receptor-mediated internalization and VRP-mediated overcoming MDR could be beneficial in treatment of MDR solid tumors by targeting delivery of micellar PTX into tumor cells. As a result, the difunctional micelle systems is a very promising approach to overcome tumor drug resistance.
研究领域:
药学科学
·
肿瘤学
·
药物递送系统
·
癌症治疗
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高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2017
·
IF 3.981
Pengfei Li,Ting Wang,Fuhou Lei,Xiaoyu Peng,Haiyang Wang,Liting Qin,Jianxin Jiang
In this study, molecularly imprinted polymer (MIP) microspheres for paclitaxel (PTX) were prepared by microsuspension polymerization and used as a stationary phase in high-performance liquid chromatography (HPLC) for the separation of PTX and its structural analog docetaxel (DOC). For MIP synthesis, ethylene glycol maleic rosinate acrylate and 2-vinylpyridine were used as the cross-linker and functional monomer, respectively. MIP microspheres were characterized by scanning electron microscopy, laser granulometry, nitrogen sorption porosimetry, and thermogravimetric analysis. Results indicated the formation of regular MIPs with an even pore size distribution; furthermore, these MIPs exhibited excellent thermal stability. These MIP microspheres were packed into a stainless steel column for the selective separation of PTX and DOC. Under optimum chromatographic conditions, a separation factor of 2.54 and an imprinting factor of 2.37 were obtained. In addition, thermodynamic data obtained from van’t Hoff plots revealed enthalpy-driven separation and higher contribution from functional group interactions as compared with that from steric complementary interactions. Microcalorimetry was employed to investigate the binding mechanisms of the analytes on the MIP surface.
研究领域:
分析化学
·
药物分析
·
材料科学
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Pharmaceuticals
·
2022
·Vol. 16
·期 1
·9
·
IF 5.215
Chunyu Wu,Chenping Sun,Xianghui Han,Yiyi Ye,Yuenong Qin,Sheng Liu
Sanyin formula (SYF) is used as a complementary treatment for triple-negative breast cancer (TNBC). The purpose of this study was to identify the potential functional components and clarify the underlying molecular mechanisms of SYF in TNBC. High-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) was used to identify the main components of SYF extracts. Network pharmacology and bioinformatic analyses were carried out to identify potential candidate targets of SYF in TNBC. Cell proliferation was determined with a Celigo imaging cytometer. Wound-healing and Transwell assays were adopted to evaluate cell migration. A Transwell cell-invasion assay was performed with Matrigel-coated membranes. In vivo bioluminescence imaging (BLI) and pathological analyses illustrated the effect of SYF on cancer cell metastasis in tumour-bearing mice. The inhibitory mechanism of SYF was investigated via quantitative PCR (qPCR) and Western blotting. We found that 3,4-dihydroxyphenyllactic acid, kaempferol, p-coumaric acid, and vanillic acid may be the active components of SYF. Molecular docking confirmed that kaempferol, p-coumaric acid, vanillic acid, and 3,4-dihydroxyphenyllactic acid bound stably to proteins such as AKR1C3, MMPs, and STAT3. SYF extract suppressed TNBC cell proliferation, migration, invasion, and metastasis by inhibiting JAK/STAT3 signalling and then regulating downstream genes, such as MMP-2/MMP-9. SYF regulates the expression of genes involved in cell proliferation, migration, and invasion by regulating the JAK/STAT3 signalling pathway and finally inhibits tumour cell metastasis in TNBC. The present study clarifies the mechanism by which SYF inhibits TNBC metastasis and lays an experimental foundation for the continued clinical development of SYF targeting the JAK/STAT3 pathway.Keywords:Sanyin formula (SYF);triple-negative breast cancer (TNBC);signal transducer and activator of transcription 3 (STAT3) pathway;cancer cell metastasis;network pharmacology
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症研究
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PubMed
高影响因子
Molecular BioSystems
·
2017
·Vol. 13
·期 10
·2125-2134
·
IF 2.781
Qianqian Wang,Fei Lu,Rongfeng Lan
Overcoming chemoresistance will prevent cancer relapse and contribute to clinical chemotherapy. In order to explore the underlying mechanism of chemoresistance, we firstly incubated cancer cells with a combination of cisplatin + paclitaxel (C + P) or cisplatin + paclitaxel + docetaxel (C + P + D) to mimic the treatment of cancer therapy in the laboratory. We found that polyploidy is a recurring strategy that cells adopt in response to cisplatin-based treatments. RNA-sequencing was performed to identify differentially expressed genes (DEGs) that may contribute to drug resistance. 4830 and 5518 DEGs were discovered in C + P and C + P + D resistant cells, respectively, and 4384 (73.40%) genes were shared. Possible drug resistance genes like Atg14, Abcb1b, Tbx2, Slc2a9, Slc10a3 and Slc22a18 were up-regulated while Foxm1, Bcl2, Brca1, Chek1, Hiatl1 and Abcb9 were down regulated. Genes involved in the pathways of p53 signaling, lysosomes and apoptosis were up-regulated, and in contrast, genes in the cell cycle, DNA replication, and mismatch repair pathways were down-regulated. Moreover, representative proteins relative to DEGs were examined to validate the results of RNA-seq and RT-PCR. Taken together, these results will contribute to revealing the mechanism of chemoresistance and discovering potential prognostic factors for cancer medication.
研究领域:
肿瘤学
·
分子生物学
·
基因组学
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Nanomaterials
·
2026
·Vol. 16
·期 6
·378
·
IF 4.8
Hao Li,Lin Zhang,You Long,Chao Shen,Song Zhang,Fang Chen,Nan Chen,Chenghong Huang
Paclitaxel is a first-line anticancer drug, but its low water solubility impedes bioavailability. The purpose of this study is to estalish a delivery strategy via carboxymethyl chitosan (CMCS)-encapsulated 6-deoxy-6-mercapto-β-cyclodextrins (dmβCDs)-modified concave cubic gold (CCGs) to achieve PTX release. CCGs were initially synthesized by the one-pot method and further modified by dmβCDs, the dmβCDs can effectively capture PTX molecules, followed by encapsulation with CMCS, and then prepare pH-responsive CMCS/dmβCDs/CCGs nanocarriers after lyophilization. Results indicated that desirable hexagonal CCGs with 50 ± 5 nm size can be obtained by adjusting H 2 O 2 and HClO concentration. FT-IR, Raman and XRD spectra had confirmed dmβCDs successfully grafted to the surface of CCGs. Drug loading experiments demonstrated that the nanocarrier encapsulated PTX in amorphous powder or molecular form have a capacity of 55.05 µg/mL. Drug release experiments revealed PTX release from CMCS/dmβCDs/CCGs nanocarriers carrying a typical pH-responsive profile and indicating earlier release in an acidic environment than in a neutral or alkaline environment. The proposed method can be utilized to effectually achieve high-efficiency solubilization and targeted release inside tumor cells of PTX.
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