Pharmaceuticals
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2022
·Vol. 15
·期 7
·881
·
IF 5.215
Tianyu Chen,Hui Chen,Yichun Jiang,Qi Yan,Shuling Zheng,Min Wu
In this research, KLA-modified liposomes co-loaded with 5-fluorouracil and paclitaxel (KLA-5-FU/PTX Lps) were developed, and their antitumor activity against triple-negative breast cancer (TNBC) was evaluated. KLA-5-FU/PTX Lps were prepared using the thin-film dispersion method, and their in vitro anticancer efficacy was assessed in human breast cancer cells (MDA-MB-231). An MDA-MB-231 tumor-bearing mouse model was also established to evaluate their antitumor efficacy in vivo. KLA-5-FU/PTX Lps showed enhanced cytotoxicity against MDA-MB-231 cells, improved drug delivery to mitochondria, and induced mitochondria-mediated apoptosis. The modified liposomes also showed favorable antitumor activity in vivo due to their strong ability to target tumors and mitochondria. The liposomes showed no obvious systemic toxicity. Our results suggest that KLA-5-FU/PTX Lps are a promising system with which to target the delivery of antitumor drugs to mitochondria as a treatment for TNBC.Keywords:5-fluorouracil;paclitaxel;liposomes;mitochondrial targeting;TNBC
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Materials Research Express
·
2021
·Vol. 8
·期 4
·045012
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IF 1.62
Fei Ge,Rui Qiao,Ping Song,Yugui Tao,Longbao Zhu,Weiwei Zhang,Wanzhen Li,Lin Gui
Tumors area common cause of morbidity and mortality. High treatment efficiency and low drug toxicity are key for effective tumor treatment. Here, the pH-sensitive material ZIF-90 was synthesized by the liquid-phase diffusion method for loading paclitaxel (PTX), and the targeting peptide (RGD) was prepared by the solid-phase synthesis method to modify it (RGD/PTX@ZIF-90). The skeleton of RGD/PTX@ZIF-90 collapses in the acidic tumor microenvironment, thereby releasing PTX and mediating the controlled release of the drug. ZIF-90 below 300 nm was obtained by adjusting the ratio of metal ions and organic ligands in the characterization experiment. In addition, in vitro drug release experiments showed that the drug release rate was greater at pH = 5.5 than at pH = 7.4. The lethal rate of RGD/PTX@ZIF-90 to human breast cancer cells (MCF-7) was 44.5%, which was higher than the lethal rate of PTX alone (37.3%) in the cytotoxicity experiment and apoptosis experiment. Uptake experiments revealed that RGD/PTX@ZIF-90 mainly existed in the cytoplasm of MCF-7, which suggests that the drug had successfully entered the cell to achieve the therapeutic effect. The loading of the nano-medicine carrier ZIF-90 and the modification of the targeting peptide RGD significantly improve the therapeutic effect of PTX and indicate that this system could be used to treat breast cancer.
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Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 30
·6037-6043
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IF 6.331
Xingwei Ding,Wenyan Jiang,Lina Dong,Can Hong,Zhong Luo,Yan Hu,Kaiyong Cai
To reduce the side effect of paclitaxel and enhance accumulation at the tumor site, a novel redox-responsive nanovector with excellent biocompatibility based on disulfide-linked amphiphilic polymer and magnetic nanoparticle was prepared. The system would realize PTX release due to breakage of the disulfide bond when being targeted to the tumor site by the external magnetic field. The nanovector significantly improved endocytosis and enhanced accumulation at the tumor site, with an effective inhibition of tumor cells in vitro and in vivo.
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Aging-US
·
2021
·
IF 5.682
Jianhao Xu,Liwei Ni,Fenglun Zhao,Xiaoxiao Dai,Jialong Tao,Jia Pan,Aiming Shi,Zhu Shen,Cunjin Su,Yusong Zhang
Background: This study aimed to investigate the aberrant expression of hsa_circ_0002874 in non-small cell lung cancer (NSCLC) and elucidate associated molecular mechanisms that influence apoptosis and induce paclitaxel (PTX) resistance. Methods: Inhibitors were used to downregulate circRNA or miRNA expression. pCDNA plasmid transfection and mimics were used to upregulate circRNA or miRNA expression. Dual-luciferase reporter assays were conducted to evaluate interactions between miR1273f and MDM2. Xenograft tumor models were used to assess the effect of hsa_circ_0002874 and miR1273f on tumor growth. NSCLC tissues and matched non-cancerous tissues were also collected for correlation analysis. Results: hsa_circ_0002874 acts as a sponge for miR1273f which targets MDM2/P53. The stability of the hsa_circ_0002874/miR1273f/MDM2/P53 pathway was verified by upregulating and downregulating the expression of hsa_circ_0002874 and miR1273f. hsa_circ_0002874 downregulation or miR1273f upregulation reversed the resistance of the A549/Taxol cells in xenograft models. The expression of hsa_circ_0002874 was high, and the level of MDM2 was low in NSCLC tissues. P53 was only weakly expressed in NSCLC tissues with high expression of MDM2. Conclusions: hsa_circ_0002874 is strongly expressed in NSCLC tissues and maybe a potential marker for PTX resistance. hsa_circ_0002874 downregulation could regulate miR1273f/MDM2/P53 signaling pathway to reverse the PTX resistance of NSCLC and induce apoptosis in vitro and vivo .
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Natural Product Communications
·
2020
·
IF 0.468
Ling-Li Zheng,Guan Wen,Yun-Xin Yao,Xiao-Huan Li,Feng Gao
Based on the strong activity dependence of paclitaxel (PTX; Taxol) or docetaxel (Taxotere) on the C-13 side chain, a small library of dehydroepiandrosterone, cholesterol, vitamin D2, and alkaloids talatisamine and songorine-PTX hybrids have been synthesized and evaluated for in vitro anticancer activity by MTT assay against human breast (MCF-7), colon (HCT116), lung carcinoma (A549), and renal adenocarcinoma (786-0) cancer cell lines. Most hybrids (11b, 12b, 13b, 15b, and 18b) reduced the growth of MCF-7 and 786-0 cells with low PTX sensitivity in vitro. Among the synthesized compounds, hybrid 11b was better in inhibiting the growth of the 4 cells than PTX. A relatively low IC50 value of compound 11b (8.16 ± 0.04 μM) was also examined after exposure for 48 hours. Hybrid 11b showed a proapoptotic effect in HCT116 cells evaluated by Annexin V/propidium iodide binding assay. The level of hybrid 11b leading to protective cell death in HCT116 cells was detected using western blot and not easily observed in our basic examinations.
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Pharmaceutics
·
2019
·Vol. 11
·期 12
·683
·
IF 4.773
Hongyan Zhu,Weili Han,Ye Gan,Qiaofeng Li,Xiaolan Li,Lanlan Shao,Dan Zhu,Hongwei Guo
In this study, we prepared gold nanostar (GNS) composite nanoparticles containing siRNA of cyclooxygenase-2(siCOX-2) that were modified by tumor targeting ligand 2-deoxyglucose (DG) and transmembrane peptide 9-poly-D-arginine (9R) to form siCOX-2(9R/DG-GNS). Paclitaxel loaded temperature sensitive liposomes (PTX-TSL) were surface-modified to produce PTX-TSL-siCOX-2(9R/DG-GNS) displaying homogeneous star-shaped structures of suitable size (293.93 nm ± 3.21) and zeta potentials (2.47 mV ± 0.22). PTX-TSL-siCOX-2(9R/DG-GNS) had a high thermal conversion efficiency under 808 nm laser radiation and a superior transfection efficiency, which may be related to the targeting effects of DG and increased heat induced membrane permeability. COX-2 expression in HepG2/PTX cells was significantly suppressed by PTX-TSL-siCOX-2(9R/DG-GNS) in high temperatures. The co-delivery system inhibited drug-resistant cell growth rates by ≥77% and increased the cell apoptosis rate about 47% at elevated temperatures. PTX-TSL and siCOX-2 loaded gold nanostar particles, therefore, show promise for overcoming tumor resistance.Keywords:gold nanostars;temperature sensitive liposome;siCOX-2;paclitaxel-resistance;hepatic carcinoma
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RSC Advances
·
2019
·Vol. 9
·期 60
·34837-34846
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IF 3.049
Jingjing Li,Qing Li,Meijuan He,Fan Ding,Lulu Cai,Mingming Zhao,Lina Dong,Qi Wang,Kai Xu
With the advantages and development of MRI nano-contrast agents (CAs), increasing number of MRI-based theranostic nanoparticles have emerged. Liposome, as a biosafe nanocarrier has been used phase III trial for cancer treatment. In this study, liposome was employed as a nanocarrier to co-encapsulate MRI nano-contrast agent poly(ethylene glycol)-grafted manganese oxide (PEG-MnO) and anticancer drug paclitaxel (PTX) for the fabrication of a novel theranostic nanocomplex. After being further modified with AS1411 aptamer, the obtained nanoprobe AS1411-liposome-PEG-MnO-PTX displayed the potential of simultaneous MRI diagnosis and therapy of renal carcinoma in vitro and in vivo. It was found that compared with PEG-MnO nano-CA, liposome-PEG-MnO and AS1411-liposome-PEG-MnO presented a stronger MR contrast enhancement effect in the tumor and longer retention time in the tumor region. More importantly, the introduction of AS1411 aptamer further enhanced the MRI effect and the tumor growth inhibition effect, showing its potential use as a theranostic nanoprobe for renal carcinoma.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
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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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JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2017
·Vol. 69
·期 8
·967-977
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IF 2.405
Shu Chang,Sabi-mouka Eboka M B,Wang Xiaoliang,Ding Li
ObjectivesIn this work, we designed the self-assembly peptide hydrogels to multiply therapeutic agents for improving anticancer effect and lowering adverse reaction of paclitaxel (PTX).MethodsThe folate (FA)-peptide-PTX hydrogels consist of self-assemble peptide hydrogel as nanoscale carrier, FA and RGD peptide as targeting moieties and paclitaxel as anticancer drug. The properties of hydrogels, such as morphology, size distribution, zeta potential and rheology, were investigated. Targeted specificity, biodistribution and anticancer effect were studied both in vitro and in vivo.Key findingsFolate-peptide-PTX hydrogel nanoparticles were spherical in shape with hydrodynamic diameter of approximately 137.3 ± 15.2 nm. The hydrogels could only target monolayer cancer cells but also penetrated the nuclei of cells in vitro. The in-vivo real-time imaging further demonstrated that the hydrogels preferentially accumulated in tumour and sustained release. Compared to free paclitaxel, the FA-peptide-PTX hydrogels had higher anticancer effect and lower side effect.ConclusionsThe dual-targeted drug delivery possessed strong capability of synergistic targeted delivery, long-term drug release and better biocompatibility than paclitaxel both in vitro and in vivo. The results obtained demonstrated a high potential of the proposed drug delivery system in improving the therapeutic efficacy of paclitaxel.
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2024
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IF 4.5
Huilin Lei,Yanling Liu,Shubing Fang,Weibin Chen,Zhigang Huang,Haoshi Gao,Cancheng Liao,Bohong Guo
In order to improve the targeted delivery of the drug, a novel folic acid-modified paclitaxel nanosuspensions (FA-PEG-PTX NCs) delivery system was designed in the present study, and its target delivery ability was verified in vitro and in vivo models. Paclitaxel nanosuspensions were prepared by antisolvent precipitation using folic acid-modified polyethylene glycol monostearate (FA-PEG-MA) and D - α-tocopherol polyethylene glycol succinate (TPGS) as functional stabilizers. The FA-PEG-PTX NCs had an average particle size of 195.33 ± 13.31 nm, a PDI of 0.182 ± 0.022 and a zeta potential of - 12.4 ± 0.62 mV. The drug loading (DL) and encapsulation efficiency (EE) of FA-PEG-PTX NCs were 48.45 ± 3.34 % and 96.90 ± 1.81 %. Particle morphology showed that FA-PEG-PTX NCs had a rod-shaped structure with a smooth surface. XRD and DSC indicated that PTX existed mainly in an amorphous structure in the nanocrystals. FTIR showed no chemical reaction between PTX and stabilizer but rather physical interactions. In vitro dissolution experiments showed that nanocrystals significantly improved the PTX dissolution rate. Cytotoxicity assay and apoptosis assay showed that FA-PEG-PTX NCs had a stronger inhibitory effect on the proliferation and apoptosis of folate receptor-positive cells, Bel-7402 cells, compared with PEG-PTX NCs. In vivo studies showed that FA-PEG-PTX NCs and PEG-PTX NCs had long-lasting and targeted effects. In conclusion, FA-PEG-MA seems to be a promising stabilizer with targeting properties.
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MICROCHEMICAL JOURNAL
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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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