JOURNAL OF POLYMER RESEARCH
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2017
·Vol. 24
·期 6
·1-11
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IF 1.615
Xia Shan,Gao Yang,Yu Zhe,Duan Lijie,Gao Guang Hui
A novel pH-sensitive charge reversal and self-fluorescent polymeric micelle is designed and synthesized successfully. The smart micelle is prepared based on MPEG-polyurethane multi-block copolymer, which is synthesized by polycondensation, with 1, 4-bis (hydroxyethyl) piperazine (HEP) and hydroxyl-sulfamethazine (Hydroxyl-SM) as pH-sensitive molecules and fluorescein isothiocyanate (FITC) as fluorescent segment. The resulting MPEG-polyurethane multi-block copolymer is examined by 1 H–NMR, UV-vis spectra, fluorescence spectra and an acid-base titration. Moreover, the diameter, morphology and cytotoxicity of obtained polymer micelle are measured by dynamic light scattering (DLS), transmission electron microscopy (TEM) and MTT assay. The results indicate that the micelle has a small diameter of less than 200 nm and can remain unchanged within two weeks. Zeta-potential measurement shows that the negative charge of micelle can switch into positive charge as the pH value decreasing from 9.0 to 3.0. Subsequently, the fluorescence intensity decreases significantly with the reducing of pH values. The MTT assay shows the low cytotoxicity and good biocompatibility of the MPEG-polyurethane polymeric micelles. Finally, doxorubicin (DOX) is loaded into micelles to detect in vitro release behavior. The drug loaded micelles show a faster release behavior at pH 5.0 than that at pH 7.4. Therefore, the pH-sensitive charge reversal and self-fluorescent micelle can be a potential smart carrier for delivery and controlled release of protein drug.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2025
·
IF 9.7
Fang Wang,Ke Wang,BaoRu Fang,SiQi Geng,Ying Li,HuiFeng Qian,YiNuo Lin,ZhangSen Yu
Doxorubicin-induced cardiomyopathy (DIC) is a toxic side effect that cannot be ignored during chemotherapy for malignant tumors. In this work, we synthesized a novel nano-chemotherapeutic drug based on Prussian blue nanozyme to alleviate DIC. Hollow mesoporous Prussian blue (HmPB) nanoparticles were used as a carrier to load doxorubicin (DOX) through electrostatic adsorption and obtain a novel chemotherapy drug, HmPB(DOX). I n vivo and in vitro chemotherapy efficacy and acute toxicity evaluation experiments were conducted. The results suggest that HmPB(DOX) exhibits pH-responsive characteristics and minimizes the release of DOX from within HmPB(DOX) in cardiomyocytes. However, in the acidic tumor microenvironment, the release of DOX from HmPB(DOX) is notably enhanced. More importantly, HmPB(DOX) possesses excellent antioxidant enzyme activity, effectively clearing DOX-induced reactive oxygen species (ROS) and alleviating oxidative stress in cardiomyocytes. Doxorubicin is pivotal in the chemotherapy of malignant tumors. This study presents novel insights for mitigating the toxic and side effects of DOX, offering new strategies to enhance tolerance to chemotherapy.
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BIOMEDICINE & PHARMACOTHERAPY
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2024
·
IF 6.9
Jingmou Yu,Yifei Zhang,Meilin Xu,Dengzhao Jiang,Wenbo Liu,Hongguang Jin,Pu Chen,Jing Xu,Lei Zhang
Herein, we constructed innovative reduction-sensitive and targeted gelatin-based micelles for doxorubicin (DOX) delivery in tumor therapy. AS1411 aptamer-modified gelatin-ss-tocopherol succinate (AGSST) and the control GSST without AS1411 modification were synthesized and characterized. Antitumor drug DOX-containing AGSST (AGSST-D) and GSST-D nanoparticles were prepared, and their shapes were almost spherical. Reduction-responsive characteristics of DOX release in vitro were revealed in AGSST-D and GSST-D. Compared with non-targeted GSST-D, AGSST-D demonstrated better intracellular uptake and stronger cytotoxicity against nucleolin-overexpressed A549 cells. Importantly, AGSST-D micelles showed more effective killing activity in A549-bearing mice than GSST-D and DOX⋅HCl. It was revealed that AGSST-D micelles had no obvious systemic toxicity. Overall, AGSST micelles would have the potential to be an effective drug carrier for targeted tumor therapy.
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Nanomaterials
·
2018
·Vol. 8
·期 3
·167
·
IF 3.504
Muyang Yang,Lixia Yu,Ruiwei Guo,Anjie Dong,Cunguo Lin,Jianhua Zhang
Synergistic combination therapy by integrating chemotherapeutics and chemosensitizers into nanoparticles has demonstrated great potential to reduce side effects, overcome multidrug resistance (MDR), and thus improve therapeutic efficacy. However, with regard to the nanocarriers for multidrug codelivery, it remains a strong challenge to maintain design simplicity, while incorporating the desirable multifunctionalities, such as coloaded high payloads, targeted delivery, hemodynamic stability, and also to ensure low drug leakage before reaching the tumor site, but simultaneously the corelease of drugs in the same cancer cell. Herein, we developed a facile modular coassembly approach to construct an all-in-one multifunctional multidrug delivery system for the synergistic codelivery of doxorubicin (DOX, chemotherapeutic agent) and curcumin (CUR, MDR modulator). The acid-cleavable PEGylated polymeric prodrug (DOX-h-PCEC), tumor cell-specific targeting peptide (CRGDK-PEG-PCL), and natural chemosensitizer (CUR) were ratiometrically assembled into in one single nanocarrier (CUR/DOX-h[email protected]NPs). The resulting CUR/DOX-h[email protected]NPs exhibited several desirable characteristics, such as efficient and ratiometric drug loading, high hemodynamic stability and low drug leakage, tumor intracellular acid-triggered cleavage, and subsequent intracellular simultaneous drug corelease, which are expected to maximize a synergistic effect of chemotherapy and chemosensitization. Collectively, the multifunctional nanocarrier is feasible for the creation of a robust nanoplatform for targeted multidrug codelivery and efficient MDR modulation.Keywords:modular coassemble;synergistic codelivery;polymeric prodrug;stimulisensitive release;biocompatibility
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2018
·
IF 2.297
Hailiang Feng,Yu Sun,Jianhua Zhang,Liandong Deng,Anjie Dong
Undesired physiological instability remains a major limitation for nanoparticle-based drug delivery. To overcome this issue, a dual pH-responsive supramolecular layer-crosslinked nanoparticles (PCB- b -PCD/PBM- b -PDPA NPs, PDM NPs), which consisted of pH-responsive hydrophobic poly(diisopropylethyl methacrylate) (pKa ≈6.3) as the core, hydrophilic poly((methacrylic acid betaine) methyl methacrylate) as the shell and pH-responsive supramolecular crosslinked layer based on β-cyclodextrin and benzimidazole (pKa <6.0), was prepared. Effects of this supramolecular layer-crosslinked structure on dilution and stored stability, protein adsorption, and pH-responsibility were investigated. PDM NPs exhibited lower critical aggregation concentrations, good unimodal distribution and better dilution stability in comparison with non-crosslinked PCB-PDPA NPs. Moreover this pH-responsive supramolecular layer-crosslinked structure did not only influence the anti-protein adsorption ability, but also reduced the disintegrated pH (from 6.3 to below 6.0) of PDM NPs, which leads to the DOX was released from PDM NPs at the mildly acid condition effectively and sustainably in vitro . Therefore, this pH-responsive layer-crosslinked NPs held promising potentials as a smart nanocarriers for drug delivery.
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Artificial Cells Nanomedicine and Biotechnology
·
2018
·
IF 3.026
Shunxiu Cao,Jiamin Guo,Yujing He,Murad Alahdal,Shanshan Tang,Yuekui Zhao,Zhaocong Yang,Huashan Gao,Wenjun Hu,Hulin Jiang,Lianju Qin,Liang Jin
The main challenge of anticancer drugs is poor tumor targeting. Now cellular carriers are widely investigated to deliver anticancer agents. As an ideal cellular candidate, human umbilical cord derived mesenchymal stem cells (hUC-MSCs) possess inherent tropism potential to tumor. Here, we constructed hUC-MSCs carrying transferrin-inspired-nanoparticles that contain doxorubicin(hUC-MSCs-Tf-inspired-NPs) to achieve enhanced anti-tumor efficacy and made an evaluation. Results represented that hUC-MSCs-Tf-inspired-NPs not only exhibit the controlled-release property of Tf-inspired-NPs, but also integrate tumor tropism and penetrative abilities of MSCs. The tumor volume of nude mice bearing breast cancer MCF-7 treated with hUC-MSCs-Tf-inspired-NPs, was remarkably reduced compared to those treated with free drug or Tf-inspired-NPs. Thus, Tf-inspired-NPs loaded hUC-MSCs have a potential to deliver anticancer drugs.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xin Chen,Fulin Luo,Mengting Yuan,Chongbin Bai,Qian Chen,Kui Zhang,Yaohua Fan,Chenxi Cao,Lei Wang,Fei Ye,Jia Jin
In clinical solid tumor treatment, intraoperative bleeding, compromised postoperative recovery, and increased non-specific toxicity from chemotherapy are always challenges. To address these limitations, we developed and well characterized novel alginate/chitosan-based hemostatic microspheres loaded with doxorubicin liposomes. The multifunctional microspheres exhibited optimal drug loading capacity and excellent drug encapsulation efficiency. Remarkably, this unique structural composition enhanced the hemostatic performance by improving their swelling and adhesion properties, surpassing those of commercial hemostatic microspheres CELOX® in both rat tail amputation and hepatic injury models. In a tumor recurrence model, SCs-lip microspheres, designed with a multi-release in situ drug delivery system, achieved sustained release of doxorubicin over an extended period, effectively reducing its toxic side effects while enhancing therapeutic efficacy. Biocompatibility experiments further validated the safety profile of this multifunctional materials. The development of this drug delivery system presents a promising opportunity to bridge the “treatment gap” between solid tumor resection surgery and chemotherapy, offering a potentially transformative approach for the application of anti-tumor drugs.
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PHYTOMEDICINE
·
2024
·
IF 6.7
Xuan Jiang,Manli Wang,Guoliang Cui,Yuanyuan Wu,Zhonghong Wei,Suyun Yu,Aiyun Wang,Wei Zou,Yanhong Pan,Xiaoman Li,Yin Lu
Background Tetramethylpyrazine (TMP), a key bioactive constituent derived from Ligusticum wallichii Franchat , has demonstrated efficacy in mitigating multidrug resistance (MDR) in human breast cancer (BC) cells. However, the precise mechanisms underlying its action remain poorly understood. Purpose Cancer stem cells (CSCs) are widely recognized as the primary contributors to MDR. This investigation seeks to elucidate the role and mechanisms through which TMP counteracts MDR by attenuating CSC-like characteristics. Methods Various assays, including flow cytometry, sphere formation, and Western blotting, were employed to evaluate TMP's effects on breast cancer stem cell (BCSC)-like phenotypes in vitro. In vivo , extreme limiting dilution assays and immunohistochemistry (IHC) were executed to assess the impacts of TMP on BCSC frequency and the levels of stemness markers. Mechanistically, RNA sequencing was performed to uncover the key biological processes involved in TMP's effects on BCSCs. Further experiments, encompassing micro scale thermophoresis (MST), drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA) and amino acid mutation analyses, were utilized to identify the essential targets and corresponding binding sites of TMP. Finally, the effects of TMP on BCSC-like phenotypes were confirmed using cells with mutated amino acid residues, which allowed us to investigate the specificity of TMP's binding sites. To further evaluate the impact of TMP on drug resistance, doxorubicin-resistant MCF7 (MCF-7 ADR ) cells, along with corresponding cell lines harboring mutated amino acid residues, were employed. Results TMP was found to inhibit BCSC-like properties both in vitro and in vivo , evidenced by a reduction in the CD44 + /CD24 - population, sphere formation capability, and expression of stemness markers. Mechanistic studies revealed that TMP targets 3‑hydroxy-3-methylglutaryl-CoA reductase (HMGCR), a rate-limiting enzyme in cholesterol biosynthesis. TMP binds to Asp-767 of HMGCR, thereby inhibiting its activity and reducing cholesterol synthesis. The influence of TMP on BCSC-like phenotypes was nullified by overexpression of wild-type HMGCR, while mutations in the binding site of HMGCR had no effect on TMP's inhibition of BCSC-like properties. Additionally, TMP mitigated MDR by targeting HMGCR. Conclusion These findings suggest that TMP alleviates MDR by reducing BCSC-like traits through targeting HMGCR and disruption of cholesterol biosynthesis in BC. This provides new insights into the mechanisms through which TMP alleviates MDR and offers new lead compound for exploring HMCGR antagonists.
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Alexandria Engineering Journal
·
2024
·
IF 6.2
Zhenjun Wang,Zongtao Xie,Chuanxin Liu,Xiaojun Zhang
The active ingredient in traditional Chinese medicine, silybin (SBN), is known to inhibit the proliferation of cancer cells and synergistically enhance the anticancer effects of the chemotherapy drug doxorubicin (DOX). However, the combination of SBN and DOX faces challenges such as a lack of targeting, short half-lives, different administration routes, and pharmacokinetic processes, which prevent the drug combination from effectively targeting tumors and diminish their synergistic potential, thereby limiting their in vivo antitumor effects. In response, this study proposes the development of a novel nanocarrier system based on molybdenum disulfide (MoS₂) modified with polyethylene glycol (PEG) and sialic acid (SA) to co-deliver SBN and DOX. This system is designed to trigger the release of the drugs in response to dual stimuli of pH and near-infrared light, increasing the intracellular concentration of the drugs and enhancing their synergistic interaction. The MoS₂-LPN-SBN/DOX nanosystem circulates within the body and specifically accumulates at tumor sites due to the enhanced permeability and retention (EPR) effect and SA-mediated active targeting. Upon exposure to near-infrared light, the system provides combined chemo- and photothermal therapy, leading to significant tumor suppression. This research offers a new approach and strategy for the clinical treatment of lung cancer, suggesting a promising pathway for enhancing the efficacy of traditional therapies.
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MICROCHIMICA ACTA
·
2025
·Vol. 192
·期 9
·1-15
·
IF 5.3
Xue Boyang,Li Qiang,Xing Yanjiao,Mu Hongkai,Yang Yongzhen,Chen Lin,Yu Shiping,Guo Rongrong
To overcome the dual challenges of suboptimal therapeutic outcomes and delayed detection in hepatocellular carcinoma (HCC), a nucleus-targeting theranostic nanoplatform based on gadolinium-functionalized carbon dots (GdCDs) is presented. GdCDs were synthesized via a one-step hydrothermal method utilizing neutral red and citric acid as carbon precursors and gadolinium chloride hexahydrate as the paramagnetic source, showing good fluorescence (FL) and magnetic resonance imaging (MRI) capabilities. After modified with a nuclear localization sequence (NLS), GdCDs were loaded with doxorubicin (DOX) to yield the integrated theranostic platform: Nucleus-targeting gadolinium-functionalized carbon dot drug delivery system (NT-GdCDs-DDS) for FL/MRI dual-modality imaging and nucleus-targeting drug delivery. NT-GdCDs-DDS exhibited optimal excitation/emission wavelengths at 497/596 nm, a high longitudinal relaxivity (r 1 ) of 23.11 mM −1 s −1 , and a DOX loading efficiency of 61.9%. Results of antitumor activity assays in vitro demonstrated the viability of HepG2 cells incubated with 400 μg/mL NT-GdCDs-DDS for 24 h was 8.12%, demonstrating strong antitumor activity. Furthermore, a significant tumor growth suppression in mice was observed by treated with NT-GdCDs-DDS over a 15-day period, showing superiority to free DOX. These findings establish NT-GdCDs-DDS as a potent theranostic nanoplatform for simultaneous HCC imaging and therapy. Graphical abstract
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Materials Today Communications
·
2025
·
IF 4.5
Rongkang Yu,Shuyue Wu,Ruibo Zhao,Han Zhang,Yao Li,Xiangdong Kong
Transcatheter arterial chemoembolization (TACE) is considered a critical treatment for hepatocellular carcinoma, but conventional embolic agents remain challenging in drug release profiles and embolization precision. Herein, we fabricated polyvinyl alcohol (PVA) concave round cake-like microspheres crosslinked with boric acid (H 3 BO 3 ) for enhanced drug delivery and embolization. PVA microspheres loaded with doxorubicin (DOX) were constructed using a crosslinking-assisted solvent evaporation method, with size control through calibrated needles. The microspheres were characterized for morphology, drug loading, release kinetics, and mechanical properties using techniques such as SEM, FTIR, TGA, XRD, and compression tests. The microspheres demonstrated over 85 % drug encapsulation efficiency and a maximum drug loading of 66.8 % w/w. In vitro cytotoxicity assays showed significant dose-dependent anticancer activity against HepG2 cells. Furthermore, the concave round cake-like microspheres exhibited excellent biocompatibility with human umbilical vein endothelial cells (HUVECs) and minimal hemolytic activity. Embolization simulations confirmed effective vascular occlusion. These results suggest that DOX-loaded PVA microspheres, with controlled drug release and robust embolic efficacy, represent a promising dual-function agent for TACE.
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Chemistry-An Asian Journal
·
2025
·
IF 3.3
Xiaoqing Jia,Yingfeng Wei,Xinyuan Zhang,Qiuping Gu,Youshun Liu,Shige Wang,Chunping Zhu
A dual-drug-loaded γ-polyglutamic acid (γ-PGA) hydrogel was synthesized, integrating third-generation dendrimers (G3) as cross-linkers for the simultaneous encapsulation of hydrophilic doxorubicin (DOX) and hydrophobic camptothecin (CPT). This hydrogel, formed via an efficient EDC/NHS-mediated reaction, demonstrated a biocompatible, porous, and pH-responsive network. The hydrophobic core of G3 significantly enhanced CPT loading, while γ-PGA facilitated effective DOX incorporation. Controlled drug release was observed, with DOX releasing faster in acidic tumor-like environments, optimizing therapeutic impact at the tumor site. In vitro studies highlighted the hydrogel's high biocompatibility and synergistic anticancer efficacy, reducing CT26 colon cancer cell viability more effectively than single-drug systems. In vivo experiments confirmed substantial tumor suppression, prolonged survival, and the absence of systemic toxicity in murine models. These results underscore the potential of this dual-drug delivery platform as a robust, multifunctional system for cancer therapy. The biocompatibility, degradability, and tailored drug release characteristics make this hydrogel a promising candidate for clinical translation, offering a novel solution for enhancing cancer treatment efficacy while minimizing side effects.
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