PeerJ
·
2023
·
IF 2.7
Liang Chen,Yi Xu
Scalp cooling is the most approved treatment for preventing chemotherapy-induced alopecia (CIA). However, the protective mechanism of scalp cooling has rarely been reported. The goal of the present study was to study the relationship between paclitaxel concentration and temperature and the inhibitory effect of low temperature on paclitaxel-induced alopecia. The results showed that the dose of paclitaxel should not exceed 60–70 mg/mL during scalp cooling treatment, and the optimal cooling temperature under different paclitaxel concentrations was determined. Normal human epidermal keratinocytes (NHEK) cells were analyzed by global transcriptome analysis, functional annotation and pathway analysis of differentially expressed genes (DEGs) and ELISA kit to analyze the mechanism of low temperature therapy. The expression of HSPA8, HSPA1A and HSPA1B, which belongs to HSP70, was up-regulated by low temperature. These genes are important target genes of low temperature treatment, which were confirmed by ELISA. The up-regulation of PLK2 and the down-regulation of TXNIP expression are the upstream of mitochondrial dysfunction and ROS, inhibiting the accumulation of ROS and up-regulating the mitochondrial membrane potential. Our research partially elucidates the therapeutic mechanism of scalp cooling, which provides a new idea on the drug research and development in CIA.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·Vol. 12
·期 19
·2203118
·
IF 10
Yi-fan Miao,Qing Ye,Ming-yang Zhang,Lin Gao,Xi-yan Wang,Wen-xin Zhong,Zi-xuan Wang,Zhong-gui He,Chu-tong Tian,Jin Sun
Owing to the serious clinical side effects of intravenous Taxol, an oral chemotherapeutic strategy is expected to be promising for paclitaxel (PTX) delivery. However, its poor solubility and permeability, high first-pass metabolism, and gastrointestinal toxicity need to be overcome. A triglyceride (TG)-like prodrug strategy facilitates oral drug delivery by bypassing liver metabolism. However, the effect of fatty acids (FAs) in sn-1,3 on the oral absorption of prodrugs remains unclear. Herein, a series of TG-mimetic prodrugs of PTX is explored with different carbon chain lengths and degrees of unsaturation of FAs at the sn-1,3 position in an attempt to enhance oral antitumor effect and to guide the design of TG-like prodrugs. Interestingly, the different FA lengths exhibit great influence on in vitro intestinal digestion behavior, lymph transport efficiency, and up to fourfold differences in plasma pharmacokinetics. The prodrug with long-chain FAs shows a more effective antitumor effect, whereas the degree of unsaturation has a negligible impact. The findings illustrate how FAs structures affect the oral delivery efficiency of TG-like PTX prodrugs and thus provide a theoretical basis for their rational design.
研究领域:
药剂学
·
肿瘤学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineering-Basel
·
2023
·Vol. 10
·期 4
·399
·
IF 4.6
Mengdi Liang,Fang Li,Yongfeng Wang,Hao Chen,Jingjing Tian,Zeyu Zhao,Karl H. Schneider,Gang Li
In-stent restenosis caused by tumor ingrowth increases the risk of secondary surgery for patients with abdominal aortic aneurysms (AAA) because conventional vascular stent grafts suffer from mechanical fatigue, thrombosis, and endothelial hyperplasia. For that, we report a woven vascular stent-graft with robust mechanical properties, biocompatibility, and drug delivery functions to inhibit thrombosis and the growth of AAA. Paclitaxel (PTX)/metformin (MET)-loaded silk fibroin (SF) microspheres were self-assembly synthesized by emulsification-precipitation technology and layer-by-layer coated on the surface of a woven stent via electrostatic bonding. The woven vascular stent-graft before and after coating drug-loaded membranes were characterized and analyzed systematically. The results show that small-sized drug-loaded microspheres increased the specific surface area and promoted the dissolution/release of drugs. The stent-grafts with drug-loaded membranes exhibited a slow drug-release profile more for than 70 h and low water permeability at 158.33 ± 17.56 mL/cm2·min. The combination of PTX and MET inhibited the growth of human umbilical vein endothelial cells. Therefore, it was possible to generate dual-drug-loaded woven vascular stent-grafts to achieve the more effective treatment of AAA.Keywords:stent-graft;silk fibroin;drug release;paclitaxel;metformin
研究领域:
生物医学工程
·
药学
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Analysis and Testing
·
2023
·Vol. 7
·期 3
·204-214
·
IF 4.7
Zhu Qiming,Li Peizhe,Huang Qiwen,Ding Xinpei,Wang Nan,Yao Weijun,Miao Maozhong,Zhang Zhijun
Building self-assembly nanostructures is an important way to overcome the limitations of paclitaxel in tumor therapy. However, this strategy is also faced with challenges, such as difficulties in efficient release and the potential for drug resistance. Herein, we developed a near-infrared light-activatable melanized paclitaxel self-assembly nanoparticles for synergistic anti-tumor therapy. In this strategy, paclitaxel dimer prodrugs were synthesized and paclitaxel nanoparticles were obtained through self-assembly. Finally, the paclitaxel dimer nanoparticles were capped with polydopamine (PDA, melanoidin) and human serum albumin (HSA). The disulfide bonds in paclitaxel dimeric prodrug specifically respond to high concentrations of glutathione (GSH) and reactive oxygen species (ROS) in tumor cells. PDA enhances the biocompatibility of the drug molecules and imparts near-infrared photothermal conversion capability to the nano–self-assemblies. Both the in vitro and in vivo experiments demonstrated that this paclitaxel nanoprodrug exhibited enhanced tumor therapeutic efficacy under near-infrared light irradiation.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
Molecular Medicine Reports
·
2023
·Vol. 28
·期 4
·1-13
·
IF 3.4
Qi Nie,Wenqing Chen,Tianmei Zhang,Shangrong Ye,Zhongyu Ren,Peng Zhang,Jian Wen
In recent years, inhibiting tumor cell activity by triggering cell ferroptosis has become a research hotspot. The development of generic targeted nanotherapeutics might bring new ideas for non‑invasive applications. Currently, the potential mechanism underlying the universal application of paclitaxel (PTX)‑loaded iron oxide nanoparticles (IONP@PTX) to different types of tumors is unclear. The present study aimed to prepare IONP@PTX for targeted cancer therapy and further explore the potential mechanisms underlying the inhibitory effects of this material on the NCI‑H446 human small cell lung cancer and brain M059K malignant glioblastoma cell lines. First, a CCK‑8 assay was performed to determine cell viability, and then the combination index for evaluating drug combination interaction effect was evaluated. Intracellular reactive oxygen species (ROS) and lipid peroxidation levels were monitored using a DCFH‑DA fluorescent probe and a C11‑BODIPY™ fluorescent probe, respectively. Furthermore, western blotting assay was performed to determine the expression of autophagy‑ and iron death‑related proteins. The experimental results showed that, compared with either IONP monotherapy, PTX monotherapy, or IONP + PTX, IONP@PTX exerted a synergistic effect on the viability of both cell types, with significantly increased total iron ion concentration, ROS levels and lipid peroxidation levels. IONP@PTX significantly increased the expression of autophagy‑related proteins Beclin 1 and histone deacetylase 6 (HDAC6) in both cell lines (P<0.05), increased the expression of light chain 3 (LC3)‑II/I in NCI‑H446 cells (P<0.05) and decreased that of sequestosome1 (p62) in M059K cells (P<0.05). Moreover, the addition of rapamycin enhanced the IONP@PTX‑induced the upregulation of Beclin 1, LC3‑II/I and HDAC6 and the downregulation of mTORC1 protein in both cell lines (P<0.05). Moreover, rapamycin enhanced the IONP@PTX‑induced downregulation of p62 protein in NCI‑H446 cells (P<0.05), suggesting that IONP@PTX induces ferroptosis, most likely through autophagy. Collectively, the present findings show that IONP works synergistically with PTX to induce ferroptosis via the autophagic pathway.
研究领域:
纳米技术
·
癌症治疗
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2025
·
IF 5.4
Yingchun Zeng,Jingxuan Yang,Ka Wang,Huan Xu,Yue Zheng,Songxin Guo,Jingwen Luo,Sha Liu,Xin Ming,Xue Ying
Combination therapy is a promising strategy for clinically nonresectable colorectal cancer (CRC) treatment, but its efficacy is compromised by challenges such as cumbersome dosing regimens, poor targeting, high toxicity, and rapid drug clearance. To address these limitations, we designed a functional multitargeted polymeric nanoparticle system (PTX+ATE+BEV-TNPs) modified with octreotide (OCT) and chondroitin sulfate (CS) as targeting ligands to simultaneously encapsulate the chemotherapeutic drug paclitaxel (PTX), the anti-PD-L1 antibody atezolizumab (ATE), and the anti-VEGF antibody bevacizumab (BEV) for triple combination therapy of CRC. The optimized nanoparticles exhibited high endocytosis efficiency and effective lysosome escape, significantly inhibiting the proliferation of tumor cells and promoting their apoptosis. Following systemic administration, PTX+ATE+BEV-TNPs could effectively achieve tumor-targeted codelivery of small-molecule drugs and macromolecular antibodies, promising therapeutic outcomes and displaying good biocompatibility in a CRC mouse model. Overall, PTX+ATE+BEV-TNPs present a viable strategy for CRC and other cancer treatments, demonstrating potential for future translational applications.
研究领域:
纳米医学
·
肿瘤学
·
药物递送
·
癌症免疫治疗
·
药用纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Innovation
·
2025
·Vol. 20
·期 1
·1-18
·
IF 2.7
Wang Kaibin,Li Yanqiang,Zhao Xiaoliang,Zhu Tianke,Luo Li,Zhang Hanwen,Wang Yonggang,Zhang Jing,Wang Cunjin,Zhang Weijie
Purpose Chinese medicine polysaccharide are considered as promising medical materials due to their good biocompatibility and safety. The aim of this study was to develop a novel amphiphilic drug carrier based on astragalus polysaccharide (APS) to optimise the delivery of paclitaxel. Methods The pH-sensitive histidine (His) and hydrophobic stearic acid (SA) were grafted onto astragalus polysaccharide and self-assembled into nanoparticles by ultrasonication. The nanoparticles were characterised by Fourier transform infrared (FTIR), dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), and X-ray diffraction, and tested for encapsulation efficiency (EE%), drug loading capacity(LC%) and in vitro release of paclitaxel. The effects of nanoparticles on the proliferation of immune cells RAW264.7 and breast cancer cells SUM149 were assessed by cck-8 assay, and their effects on SUM149 cell cycle block and apoptotic protein expression were detected. Results The EE% of nanoparticles on paclitaxel was 77.61% and the LC% was 9.96%. Under acidic conditions, the surface charge of nanoparticles was reversed and the structure was swollen to promote drug release. Cellular experiments showed that blank nanoparticles could promote the proliferation of immune cells, and the anticancer effect of drug-loaded nanoparticles was significantly better than that of paclitaxel alone. Conclusion The prepared pH-sensitive nanoparticles can effectively enhance the uptake of paclitaxel by tumour cells and induce apoptosis in breast cancer cells, making them a promising new type of paclitaxel drug carrier.
研究领域:
药剂学
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纳米医学
·
药物递送系统
·
天然产物
·
癌症治疗
✓ 已验证
产品关联
DOI
高影响因子
KEY ENGINEERING MATERIALS
·
2020
·
IF 0
Ming Chun Li,Mei Hua Xin
In this study, a new type of surfactant, N, N-dialkyl-3, 6-O-sulfopropyl chitosan (SPDACS) was prepared with two kinds of chitosan (Mw 10 and 50 kDa) and three kinds of alkyl groups (octyl, decyl and lauryl) respectively. The substitution degree of alkyl chain was around 1.50, and the substitution degree of sulfopropyl was around 1.70. The relationship of structure and surfactivity of chitosan-based surfactants were studied with six different structures of SPDACS.The results showed that the length of alkyl side chain and the molecular weight of chitosan main chain of SPDACS had distinct effect on the surface tension (γ) and the critical micelle concentration (CMC). CMC and γ could be reduced as the length of alkyl and the molecular weight of chitosan increased. For the products with 50 kDa of chitosan, the CMC decreased from 0.014 to 0.006 mg/mL, and γ down to 23.59 from 28.76 mN/m as the length of alkyl increased from 8C to 12C. The similar patterns happened for the products with 10 kDa of chitosan. The mean size of the blank micelles decreased with the growth of the length of alkyl, and the molecular weight of chitosan had little effect on the particle size. The zeta potential of all micelles were above -35mV which meant the micelles had good stability in the solution.The product of 5-SPDLCS (50 kDa, lauryl) with the best surfactivity were selected for the study of PTX solubilization. The optimal ratio of 5-SPDLCS/PTX was determined to be 1/1.1. The results showed the encapsulation effificiency (EE) and loading effificiency (LE) were 92.2 % and 50.36 % respectively. The solubility of PTX in water reached to 6.08 mg/mL. The solubility of PTX was 60,000 times higher than that of PTX (< 0.0001mg/mL) in pure water.
研究领域:
材料科学
·
药学
·
化学工程
✓ 已验证
DOI
Biomaterials Science
·
2016
·Vol. 4
·期 8
·1219-1232
·
IF 3.614
Kongtong Yu,Yulin Zhou,Yuhuan Li,Xiangshi Sun,Fengying Sun,Xinmei Wang,Hongyan Mu,Jie Li,Xiaoyue Liu,Lesheng Teng,Youxin Li
Research on quantitatively controlling the ligand density on the surface of nanocarriers is in the frontier and becomes a technical difficulty for targeted delivery system designing. In this study, we developed an improved pre-conjugation (Imp) strategy, in which herceptin as a ligand was pre-conjugated with DSPE-PEG2000-Mal via chemical cross-linking, followed by conjugation onto the surface of pre-prepared paclitaxel-loaded PLGA/DODMA nanoparticles (PDNs) through hydrophobic interaction and electrostatic attraction for paclitaxel delivery. Compared with the post-conjugation (Pos) strategy, in which the ligand was conjugated onto the nanoparticle surface after the preparation of the nanoparticles, it realized a precise control targeting effect via adjustment of the herceptin density on the surface of the nanoparticles. Within the range of 0–20% of DSPE-PEG2000-herceptin in the blend, it showed a linear relation with the ligand density on the surface of the nanoparticles. The Imp strategy protected the bioactivity of the ligand during the preparation of nanoparticles. At the same time it avoided the waste of an excess amount of herceptin to drive the conjugation reaction in comparison with the post-conjugation (Pos) strategy. The nanoparticles from the Imp strategy showed much better cytotoxicity (p < 0.001), tumor targeting and cellular uptake efficiency (p < 0.001) than that of the other strategies in BT474 cells, in which BT474 cells were HER2 receptor over-expression breast cancer cell lines. A significant reduction in cellular uptake of the nanoparticles from the Imp strategy was observed in the presence of sucrose and cytochalasin D, indicating that clathrin-mediated and caveolae-dependent endocytosis was as a primary mechanism of cellular entry for these antibody-modified nanoparticles.
研究领域:
药剂学
·
肿瘤学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
REACTIVE & FUNCTIONAL POLYMERS
·
2020
·
IF 3.333
Shupeng Li,Wei Zhao,Na Liang,Yingxue Xu,Yoshiaki Kawashima,Shaoping Sun
The clinical application of paclitaxel (PTX) is limited due to its low solubility and severe side effects. In this study, an amphiphilic graft copolymer based on mPEG , deoxycholic acid and N -acetyl- L -cysteine modified hyaluronic acid (mPEG-HA(DCA)-NAC) was synthesized and used as a redox-sensitive nano-sized drug delivery system. The polymer was characterized by Fourier transform infrared (FT-IR) and Proton nuclear magnetic resonance ( 1 H NMR) analysis. As an amphiphilic polymer, mPEG-HA(DCA)-NAC could self-assemble into micelles in aqueous milieu and encapsulate PTX in the hydrophobic core with high drug loading of 15.6% and high encapsulation efficiency of 73.8%. The PTX-loaded micelles had an average size of 147 nm and zeta potential of −38.3 mV. Physicochemical properties of the micelles were measured by TEM and XRD analysis . XRD analysis confirmed the successful encapsulation of PTX in an amorphous state. In vitro drug release study demonstrated the redox-sensitivity of the micelles. In vitro and in vivo antitumor efficacy study indicated that the PTX-loaded mPEG-HA(DCA)-NAC micelles had excellent antitumor effect but with low toxicity to the body. It can be concluded that the mPEG-HA(DCA)-NAC micellar system represents a promising nanocarrier for delivery of PTX.
研究领域:
药剂学
·
肿瘤学
·
生物材料
✓ 已验证
DOI
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2020
·
IF 2.22
Jiyang Liu,Na Liang,Shupeng Li,Yang Han,Pengfei Yan,Yoshiaki Kawashima,Fude Cui,Shaoping Sun
The clinical application of paclitaxel is limited due to its low solubility and severe side effects. A tumor-targeting and redox-sensitive paclitaxel-loaded micellar system could exhibit high drug solubility, excellent antitumor activity and low toxicity to normal tissues. An mPEG and hexadecanol-modified hyaluronic acid with disulfide bridges in the molecules (mPEG-S-S-HA-C16) was designed and synthesized. Using mPEG-S-S-HA-C16 as the carrier, the paclitaxel-loaded micelles were fabricated, and their physicochemical properties were studied deeply. Moreover, the antitumor evaluation of the paclitaxel-loaded micelles was conducted in vitro and in vivo. For the optimized paclitaxel-loaded mPEG-S-S-HA-C16 micelles, the average size and zeta potential were 168.6 nm and −38.2 mV, respectively. In vitro drug release study demonstrated the redox-sensitivity of the micelles that the encapsulated paclitaxel could be released rapidly in the presence of glutathione. MTT assay confirmed the low toxicity of the polymeric material itself and the excellent cytotoxicity of paclitaxel-loaded mPEG-S-S-HA-C16 micelles against MCF-7 cells. Moreover, the in vivo antitumor evaluation demonstrated the superior antitumor efficacy of the paclitaxel-loaded micelles. These results suggested that the paclitaxel-loaded mPEG-S-S-HA-C16 micelles held great promise for targeted delivery of paclitaxel.
研究领域:
药剂学
·
肿瘤学
·
生物材料
✓ 已验证
DOI
PubMed
高影响因子
Biomed Research International
·
2019
·
IF 2.197
Yu Gao,Lili Hu,Ying Liu,Xiaoyan Xu,Chao Wu
Hyaluronic acid functionalized mesoporous hollow alumina nanoparticles (HMHA) were used as a tumor-targeted delivery carrier for liver cancer therapy. Paclitaxel (PAC) incorporated in the carrier by the adsorption method was analyzed by X-ray diffraction and differential scanning calorimetry. PAC was found to be in an amorphous state. The hyaluronic acid coated on the surface of mesoporous hollow alumina nanoparticles (MHA) regulated the drug release rate and the loaded samples obtained a sustained drug release. In vitro experiments demonstrated that paclitaxel-hyaluronic acid functionalized mesoporous hollow alumina nanoparticles (PAC-HMHA) had a high cellular uptake, which increased the drug level in tumor tissues and was beneficial to promote apoptosis. An in vivo tumor inhibition rate study demonstrated that PAC-HMHA (64.633 ± 4.389%) had a better antitumor effect than that of paclitaxel-mesoporous alumina nanoparticles (PAC-MHA, 56.019 ± 6.207%) and pure PAC (25.593 ± 4.115%). Therefore it can be concluded that PAC-HMHA are a prospective tumor-targeted delivery medium and can be useful for future cancer therapy.
研究领域:
药剂学
·
肿瘤学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）