CURRENT TOPICS IN MEDICINAL CHEMISTRY
·
2021
·Vol. 21
·期 14
·1268-1284
·
IF 3.295
Zhao Ling,Liang Leyi,Guo Mimi,Li Ming,Yu Xuesong,Wang Ying,Wang Yan
Aims: Research on developing targeted delivery of anticancer drugs for the treatment of hepatocellular carcinoma (HCC) is ongoing. This study aimed to synthesize nanoliposomes modified by glycyrrhetinic acid (GA) and ferric tetroxide (Fe3O4) for targeted delivery of paclitaxel for selective
and specific therapy of HCC. Objective: During this project, GA and Fe3O4 were used to jointly modify the active targeting and magnetic orientation of paclitaxel nanoliposomes for enhanced targeting of HCC to improve the efficacy, while reducing the systemic toxicity and side effects
of the drug. Methods: In this study, liposomes were prepared utilizing a thin film dispersion method, in which the average particle size of GA/Fe3O4-PTX-LP was 148.9 ± 2.3 nm, and the average Zeta potential was -23.2 ± 3 mV. Based on TEM characterization, GA/Fe3O4-PTX-LP
is a closed particle with bilayer membranes. In vitro release assessments of the drug indicated that the release of GA/Fe3O4- PTX-LP was sustained. Results: In vitro cell tests have demonstrated that GA/Fe3O 4-PTX-LP can inhibit the proliferation, affect the morphology, migration and
invasion, and interfere with the cycle of HCC cells. Uptake tests have confirmed that GA/Fe3O4-PTX-LP can promote the uptake of the drug in HCC cells. Conclusion: In vivo targeting experiments have shown that GA/Fe3O4-PTX-LP has a strong ability to target tumors. In vivo antitumor assessments
have proven that GA/Fe3O4-PTX-LP can inhibit tumor growth without obvious toxicity. This project provides a promising nano-targeted drug delivery system for the treatment of HCC.
研究领域:
药学
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癌症研究
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纳米技术
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF MICROENCAPSULATION
·
2020
·
IF 2.287
Manling Du,Zhenjiang Yang,Wenping Lu,Bingyue Wang,Qi Wang,Zhen Chen,Lianyu Chen,Shuyan Han,Tiange Cai,Yu Cai
Aims: In this study, we prepared spirulina polysaccharides into spirulina polysaccharide-loaded nanoemulsions (SPS-NEs), and determined the antitumor effect of SPS-NEs, when combined with paclitaxel (PTX).Methods: SPS-NEs were prepared by a phase transformation method. The Characterisation and stability of SPS-NEs was measured. The antitumor effect of SPS-NEs combined with PTX was determined by S180 cells or RAW 264.7 macrophages and S180 tumour-bearing mice.Results: SPS-NEs were spherical and stable, the particle size of SPS-NEs was 84.6 ± 3.31 nm, PDI = 0.235 ± 0.02. PTX + SPS-NEs exhibited a much greater toxicity against RAW 264.7 cells than PTX. PTX + SPS-NEs increased the release of NO, IL-6 and TNF-α, and the expression of p-p65 NF-κB, p-I-κB, TLR4. In addition, PTX + SPS-NEs significantly inhibited tumour growth by 72.82% and increased the secretion of serum IL-2, TNF-α and IFN-γ.Conclusions: SPS-NEs can regulate immunity through TLR4/NF-κB signalling pathways, which enhances the anti-tumour effect of PTX.
研究领域:
药学
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癌症研究
·
纳米技术
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
·
2021
·Vol. 26
·期 9
·517-532
·
IF 4.009
Wang Y,Cui S,Wu B,Zhang Q,Jiang W
Purpose : In the present study, to achieve high paclitaxel (PTX) loading in a conjugated drug delivery system with minimal long-term side effects, we formulated a novel degradable stereocomplexed micelle-like particle with a core-shell structure. Materials and methods : In this system, methoxy polyethylene glycol (MPEG) acted as the hydrophilic shell, and the stereocomplex of polylactic acid with PTX (SCPLA-PTX) acted as the hydrophobic core. The MPEG-SCPLA-PTX micelle-like particles were synthesized via the self-assembly of a MPEG-poly L-lactic acid (PLLA) copolymer with a PTX-poly D-lactic acid-PTX copolymer. The resultant copolymers and their intermediates were characterized using 1 H nuclear magnetic resonance and GPC. Micelle-like particles with different molecular weight ratios of MPEG and PLLA were synthesized to demonstrate the functions of both components. Results : PTX loading into MPEG2000Da-PLLA6000Da particles reached as high as 20.11%. At 216 h, the cumulative release from MPEG5000Da-PLLA6000Da, MPEG2000Da-PLLA6000Da, and MPEG5000Da-PLLA22000Da particles were 51.5%, 37.7%, and 52.0%, respectively. Conclusions : According to the cell uptake experiments, inhibition of tumor cell growth was satisfactory, indicating that the stereocomplexed particles developed in the present study can be employed as a promising nanocarrier for PTX delivery.
研究领域:
药学
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纳米技术
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药物递送系统
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癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2020
·Vol. 16
·期 7
·1160-1168
·
IF 4.483
Liu Qiaoming,Cheng Meng,Liang Jianqin,Jin Yi,Feng Jianfang,Tu Liangxing
The oral administration of paclitaxel suffering obstacles like poorly solubility and low permeability, causing extremely low oral bioavailability. In this study, we aim to study the role of transmembrane pathway on the absorption mechanisms of PTX-Micelles. In addition, we will further
study the permeability of PTX-Micelles by employing in situ perfusion model. The results showed the PTX-Micelles could be up taken by caco-2 intact. In addition, we found that the endocytosis pathway and M cells pathway attended, while paracellular pathway absented in the transport
process of PTX-Micelles. The study on in situ perfusion showed the absorption rate constant (Ka) of PTX was enhanced from 6.3, 6.1, 10.6 and 13.6 × 10–2/min to 15.1, 18.4, 45.6 and 42.9 × 10–2/min by micelles in duodenum, jejunum, ileum
and colon, respectively, indicating the PTX-Micelles could enhance the permeability of PTX in intestinal membrane. This study indicating that transmembrane pathway-mediated transport is an important part in the transport process of polymeric micelles, and designing formulation based on transmembrane
pathways may be a promising route for oral bioavailability enhancement of poor-soluble drugs.
研究领域:
药学
·
药理学
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药物递送系统
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生物药剂学
✓ 已验证
DOI
PubMed
高影响因子
ANNALS OF CLINICAL AND LABORATORY SCIENCE
·
2023
·Vol. 53
·期 1
·116-125
·
IF 0.8
Yunfang Cai,Ting Zhang,Guiying Chen,Chunxi Liu
Objective Flap endonuclease 1 (FEN1) has been confirmed to involve the drug resistance of multiple cancers including breast cancer.However, the effect of miRNA-mediated FEN1 on breast cancer cell resistance is still ambiguous and needs further research. Methods Firstly, we used GEPIA2 to predict the FEN1 expression in breast cancer. Next, we used quantitative real-time polymerasechain reaction (qRT-PCR) and western blot to evaluate the FEN1 level of cells. After parental cells or MDA-MB-231-paclitaxel(PTX) cells being transfected with or without siFEN1, the apoptosis, migration, and protein levels of FEN1, Bcl-2, and resistance-relatedgenes were examined by flow cytometry, wound healing assay, and western blot, respectively. Then, the putative miRNA targetingFEN1 was predicted using StarBase V3.0, and further confirmed by qRT-PCR. The targeted binding of FEN1 to miR-26a-5p was detectedby dual-luciferase reporter assay. After parental cells or MDA-MB-231-PTX cells being transfected with or without miR-26a-5pmimic, the apoptosis, migration, and protein levels of FEN1, Bcl-2, and resistance-related genes were tested again. Results FEN1 expression was enhanced in breast cancer and MDA-MB-231-PTX cells. The combined application of FEN1 knockdown and PTXenhanced apoptosis in MDA-MB-231-PTX cells but suppressed cell migration and expressions of FEN1, Bcl-2, and resistance-relatedgenes. Then, we confirmed that FEN1 was targeted by miR-26a-5p. The combined application of miR-26a-5p mimic and PTX largelyfacilitated apoptosis in MDA-MB-231-PTX cells but restrained cell migration and expressions of FEN1, Bcl-2, and resistance-relatedgenes. Conclusion MiR-26a-5p contributes to the sensitivity of breast cancer cells to paclitaxel via restraining FEN1.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Nanoscale Horizons
·
2025
·
IF 6.6
Lin Li,Pengyao Wei,Tong Kong,Bo Yuan,Pan Fu,Yong Li,Yuhui Wang,Jianping Zheng,Kaizhe Wang
Triple-negative breast cancer (TNBC) is highly invasive with a poor prognosis, and chemotherapy remains the clinical treatment of choice. Paclitaxel is a commonly used first-line chemotherapy drug, but its untargeted distribution poses clinical challenges. Inspired by antibody–drug conjugates, we develop a precisely structured framework nucleic acid-programmed aptamer–paclitaxel conjugate (FAPC) with chemically well-defined paclitaxel loading dosing, enabling the regulation of receptor–aptamer affinity to facilitate tumor-targeted chemotherapy. Utilizing framework nucleic acids as a precise addressing scaffold, we organize the AS1411 aptamer with accurate intermolecular spacing and find that an inter-aptamer spacing of 19.04 nm could enhance the affinity of the FAPC for tumor cells. Then, the multifunctional FAPC can disrupt actin reorganization to achieve cytotoxicity in tumor cells. Furthermore, the AS1411-specifically modified FAPC further enhances the structure-dependent selective accumulation of drugs at tumor sites in a human xenograft model of triple-negative breast cancer, subsequently leading to significantly improved antitumor efficacy and reduced toxicity. The FAPC provides a precisely programmable platform for efficient targeted delivery of chemotherapeutic agents to malignancies.
研究领域:
肿瘤学
·
分子生物学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2025
·
IF 5.1
Ruicheng Rui,Yi Li,Yiming Liu,Xiaocui Li,Gaochao Zhou,Chunai Zhao,Yang Han
Natural products have attracted attention owing to their multiple antitumor effects, improved chemotherapy sensitivity, and fewer side effects. The combination of natural active ingredients and chemotherapy drugs could be an effective strategy for synergistic antitumor therapy by preserving their activity to inhibit the growth of tumor while reducing the side effects of chemotherapy drugs at relatively low doses. Although the feasibility of the delivery of natural products and chemotherapy drugs has been proven, most current carriers cannot be efficiently loaded, thus leading to a discrepancy in the drug release ratio compared to the predefined loading ratio. In this study, simple nanoassemblies with controllable drug release profiles were constructed to co-deliver paclitaxel (PTX) and dihydroartemisinin (DHA) for synergistic treatment of breast cancer. The nanoassemblies demonstrated a notable capacity for loading efficiency, micro-environmental triggering of drug release, and activation of the homodimeric prodrug at the tumor site, thereby facilitating successful combination therapy. The in vitro and in vivo antitumor effects were synergistically improved by combining DHA and PTX through prodrug modifications and nanoassemblies. Our findings provide a simple and efficient strategy for the development of nanoassemblies combining natural active ingredients with chemotherapeutic drugs.
研究领域:
药理学
·
纳米技术
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF CHEMICAL ENGINEERING
·
2026
·
IF 3.5
Minghong Feng,Teng He,Haiqian Zhao,Tao Chen,Wenjing Lin,Chufen Yang
To address the challenges of poor stability and weak targeting capability in polymeric micelles, which negatively impact controlled drug release performance, pH-responsive polymers PCL-PDEAEMA-PHEMA-PPEGMA (P1, P2, and P3) with distinct block lengths were designed and synthesized in this work. These copolymers were rigorously characterized using 1 H NMR, FT-IR, and GPC. Subsequently, polymer P3 was selected for modification based on comparative analyses of critical micelle concentrations (CMC) and drug-loading performance. Polymer P3 underwent esterification with lipoic acid (LA) and folic acid (FA) to yield LA-P3 and FA-P3, respectively. These derivatives were blended at a mass ratio of 1:1 (LA-P3:FA-P3), and dithiothreitol was employed to initiate self-crosslinking, resulting in the preparation of actively targeted crosslinked mixed micelles (C-MIX). The results revealed that C-MIX@PTX drug-loaded micelles prepared at a feeding ratio of 15 mg PTX/30 mg polymer exhibited a smaller size (134.7 nm) compared to non-crosslinked micelles, with a drug-loading content of 15.31 ± 1.79% and an encapsulation efficiency of 38.42 ± 5.22%. In vitro release studies demonstrated that under neutral conditions, C-MIX@PTX achieved a cumulative drug release of 16.8% at 120 h, significantly lower than non-crosslinked micelles. Under acidic/reductive conditions, C-MIX@PTX showed a cumulative drug release of 77.1% at 120 h, slightly lower compared to non-crosslinked micelles. Cytotoxicity assays confirmed that both MIX and C-MIX were biocompatible low-toxicity carrier materials, while LA-P3@PTX, FA-P3@PTX, MIX@PTX, and C-MIX@PTX exhibited inhibitory effects on HepG2 cells, FA-P3@PTX with folate-modified demonstrated enhanced efficacy.
✓ 已验证
产品关联
DOI
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
Materials Science & Engineering C-Materials for Biological Applications
·
2019
·
IF 4.959
Zhang-Qi Feng,Ke Yan,Jiacheng Li,Xuran Xu,Tao Yuan,Ting Wang,Jie Zheng
Paclitaxel is broad-spectrum anticancer drug which has been widely used in clinic. However, traditional drug delivery often suffers from the scarcity of resources and systemic toxic side effects caused by the localization to non-tumor areas, rendering cancer treatment extremely challenging. To address this problem, we developed a novel multifunctional drug delivery system of a poly(lactic- co -glycolic acid) (PLGA) drug-loaded magnetic Janus particles (DMJPs) using electrohydrodynamic (EDH) co-jetting. The DMJPs were loaded with three compartments each with distinct function, i.e. paclitaxel for killing cancer cell, Fe 3 O 4 nanoparticles for target location, and rhodamine B for fluorescence tracing, respectively. The Janus structure of the DMJPs, as demonstrated by the loaded nano-quantum dots CdS/ZnS and CdSe/ZnS in different compartments, enhanced not only the drug loading and encapsulation efficiency but also the cumulative release rate of the loaded drugs from DMJPs in different media. More importantly, DMJPs exhibited specific and high toxicity only to human breast cancer cells (MDA-MB-231), but not to mouse embryonic fibroblasts (NIH-3 T3). Consistently, DMJPs induced the higher lethal effect on cancer cells than paclitaxel suspension of high concentrations. Under guidance of external magnetic field, DMJPs can readily target and accumulate on and inside cancer cells for cell elimination. The specific targetability, selectivity, and toxicity of DMJPs on cancer cells would greatly avoid any potential side effects and reduce the overdose of drugs for conventional drug delivery. This work hopefully provides a new drug delivery system for the development of anticancer drug systems for clinical and precision medicine treatment.
研究领域:
药学
·
肿瘤学
·
纳米医学
✓ 已验证
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Han Liu,Wei Xia,Yujue Meng,Quangang Xu,Zihan Xia,Bahtiyor Muhitdinov,Ergang Liu,Huan Shen,Yongzhuo Huang
Psoriasis is a chronic inflammatory skin disease, notably characterized by the hyperproliferation of epidermal cells and infiltration of inflammatory cells. Paclitaxel (PTX), beyond its canonical roles in microtubule inhibition and proliferation suppression, has recently garnered increasing attention for its promising therapeutic potential in inflammatory diseases. However, PTX is constrained by its low solubility and poor permeability in topical applications. Based on the applications of Hansen Solubility Parameters in predicting coassembled systems, we herein identified a series of herb-derived small molecules with anti-inflammatory and antioxidant properties that enhance the solubility of PTX. Among them, glycyrrhizic acid not only enhanced the solubility of PTX by nearly 400-fold but also coassembled with PTX to form nanoparticles (PGNs). PGNs featured a high PTX payload (over 30%) and notable skin retention free of excipients and surfactants. PGNs were loaded into a gel, and the resultant PGN@Gel exhibited superior therapeutic efficacy against psoriasis while concomitantly mitigating cutaneous irritation. This coassembly system provides a simple yet efficient approach for solubilizing poorly soluble drugs, thereby broadening the application of PTX-based topical delivery formulations in psoriasis treatment.
研究领域:
药剂学
·
皮肤科学
·
纳米技术
·
药理学
·
炎症性疾病
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药物递送系统
·
分子组装
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2025
·Vol. 86
·期 2
·e70047
·
IF 4.2
Kangmin Chen,Yanni Zhao,Tianyang Jin,Tingxin Xu,Conglun Zhu,Hui Shen,Xiaohong Xu,Yongsheng Jiang,Yi Wang,Shihang Xue
Triple-negative breast cancer (TNBC) is difficult to treat due to the lack of clear therapeutic targets. Paclitaxel (PTX) is commonly used to treat TNBC, but drug resistance limits its effectiveness. Myeloid differentiation protein 2 (MD2) and serum amyloid A1 (SAA1) are involved in various diseases, including infections, inflammatory diseases, and cancer. We investigated their role in PTX resistance to identify potential anti-TNBC drugs. In this study, we investigated the changes of SAA1 in TNBC tissues and its role in PTX-induced TNBC cells. Our study revealed SAA1 expressed in the human TNBC subtype and TNBC cells. PTX and CIS induce SAA1 in TNBC cells, and PTX induces inflammatory response via SAA1 in TNBC cells. MD2 blockade increased the sensitivity of TNBC cells to PTX, which was related to the expression of SAA1 during PTX-caused damage of TNBC cells. In further research, SAA1 binds to MD2, promotes the combination of TLR4/MD2 and TLR4/MyD88, activates the NF-κB signaling pathway, and creates the inflammatory microenvironment for cancer cells. Our study reports for the first time that the PTX/SAA1/MD2 axis exists in the PTX-resistance process, which could be a potential treatment target of PTX-resistance.
研究领域:
肿瘤学
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）