Journal of Materials Chemistry C
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2020
·Vol. 8
·期 21
·7113-7119
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IF 7.059
Fei Yan,Jie Chen,Qifan Jin,Huaxu Zhou,Ajabkhan Sailjoi,Jiyang Liu,Weizhong Tang
Developing ordered mesoporous silica-based membranes with highly sensitive detection performance is of great significance for direct electrochemical detection in biological fluids against surface biofouling. Herein, we describe a facile one-step approach for the integration of a vertically-ordered mesoporous silica-nanochannel film (VMSF) with electrochemically reduced graphene oxide (ErGO) by an electrochemically assisted self-assembly (EASA) method. Electrochemical reduction of GO and growth of the VMSF simultaneously occur in a simple one-step process, forming a VMSF/ErGO layer on the glassy carbon electrode (GCE). Arising from the oxygen-containing groups, hydrophobic π-conjugated structure, and the two-dimensional planar structure of ErGO, the VMSF could be stably grown on the GCE surface and it further acted as a protective layer to prevent the internal ErGO electroactive layer from falling off the electrode surface over prolonged use. In comparison with a bare GCE, the present VMSF/ErGO/GCE sensor exhibits an excellent response to doxorubicin with a wide linear range (1 nM−20 μM), a high sensitivity (7.815 μA μM−1) and a low limit of detection (0.77 nM), due to the cooperative signal amplification originating from the electrocatalytic activity and π–π interaction of ErGO and electrostatic preconcentration effect of the VMSF. Furthermore, considering the outstanding anti-fouling and anti-interference ability of the VMSF, direct determination and long-term monitoring of doxorubicin in human whole blood was successfully achieved by the sensor.
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Artificial Cells Nanomedicine and Biotechnology
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2018
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IF 3.026
Yuwei Ma,Huiyi Zhou,Fan Hu,Zhichao Pei,Yongqian Xu,Qi Shuai
Nanogels exhibit potential application values in drug delivery systems because of their tunable properties and biocompatibility. In this study, multifunctional hyaluronic-based nanogels (HNPs), all-trans retinoid acid (ATRA)/aggregation-induced emission luminogen (AIEgen) fluorophores (TPENH2)-grafted hyaluronic acid (HA) with disulfide bonds as linkers of (HA-ss-ATRA/TPENH2), were successfully developed for doxorubicin hydrochloride (DOX) delivery. Besides, the controls of HA-ATRA/TPENH2 were also developed for comparison. The HNPs with nanoscale particle sizes possessed an excellent DOX-loading capacity. As expected, the DOX-loaded HNPs exhibited the higher stability in a normal physiological environment (10 µM GSH), but rapidly disintegrated in the cancer microenvironment (20 mM GSH) according to an in vitro drug release study. The intracellular observation of HNPs by the fluorescence microscopy indicated that the self-fluorescent DOX-loaded HNPs with unique AIEgen characteristic transported DOX into the cancer cells and visibly accumulated within the cytoplasm. Importantly, the accumulation of DOX-loaded HNPs was largely increased due to the targeted reorganization of CD44 or LYCE-1 receptors by HA moieties on the surface of HNPs. Based on in vitro cytotoxicity analyses, the DOX-loaded HNPs displayed dramatically enhanced virulence to cancer cells compared to the controls and free DOX. This is the first study to achieve combined functionalities of targeted delivery, controllable release and real-time intracellular imaging on HA-base nanogels with enhanced antitumor efficiency. Therefore, the multifunctional HA-ss-ATRA/TPENH2 HNPs have good potential to develop a novel drug delivery platform for the targeted delivery and controlled release of DOX to achieve enhanced antitumor efficiency as well as real-time intracellular imaging.
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Journal of Materials Chemistry B
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2017
·Vol. 5
·期 46
·9157-9164
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IF 4.543
Long Xu,Mingying Zhao,Yidi Yang,Yan Liang,Changzhen Sun,Wenxia Gao,Sai Li,Bin He,Yuji Pu
Low molecular weight gels (LMWGs) have significant advantages in drug delivery such as high drug loading capacity, in situ delivery of drug to the lesion site, sustaining drug release with excellent bioavailability, and minimized side effects. Here, we synthesized a reactive oxygen species (ROS)-responsive gelator to prepare an injectable gel. An anticancer drug, doxorubicin hydrochloride (DOX), and a photosensitizer, Zn(II) phthalocyanine tetrasulfonic acid (ZnPCS4), were loaded into the gel for combined chemo-photodynamic therapy. The ROS-responsive gelator was characterized by proton nuclear magnetic resonance (1H NMR) and the morphology of gels was investigated by scanning electron microscopy (SEM). The rheological properties and destruction–recovery capability of both blank and drug-loaded gels were studied. The cytotoxicity of LMWGs against 3T3 fibroblasts and 4T1 breast cancer cells was tested. The in vitro drug release of both drugs was studied and the in vivo anticancer activities of DOX–ZnPCS4-coloaded LMWGs were investigated in tumor-bearing mice. The results revealed that the injectable ROS-responsive DOX–ZnPCS4-coloaded LMWGs exhibited excellent anti-tumor efficacy by a synergistic therapy.
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BIOMACROMOLECULES
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2015
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IF 5.75
Jianming Pan,Runrun Wu,Xiaohui Dai,Yijie Yin,Guoqing Pan,Minjia Meng,Weidong Shi,Yongsheng Yan
We chemically integrated mesoporous silica nanoparticles (MSNs) and macroporous bowl-like polylactic acid (pBPLA) matrix, for noninvasive electrostatic loading and long-term controlled doxorubicin (DOX) release, to prepare a hierarchical porous bowl-like pBPLA@MSNs-COOH composite with a nonspherical and hierarchical porous structure. Strong electrostatic interaction with DOX rendered excellent encapsulation efficiency (up to 90.14%) to the composite. DOX release showed pH-dominated drug release kinetics; thus, maintaining a weak acidic pH (e.g., 5.0) triggered sustained release, suggesting the composite’s great potential for long-term therapeutic approaches. In-vitro cell viability assays further confirmed that the composite was biocompatible and that the loaded drugs were pharmacologically active, exhibiting dosage-dependent cytotoxicity. Additionally, a wound-healing assay revealed the composite’s intrinsic ability to inhibit cell migration. Moreover, pH- and time-dependent leaching of the integrated MSNs due to pBPLA matrix degradation allow us to infer that the leached (and drug loaded) MSNs may be engulfed by cancer cells contributing to a second wave of DOX-mediated cytotoxicity following pH-triggered DOX release.
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JOURNAL OF ETHNOPHARMACOLOGY
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2024
·
IF 4.8
Peijun Sun,Huixian Chen,Xiaoyu Fan,Jiayi Wang,Lujie Lu,Guangchao Yang,Jining Liu,Weifeng Yao,Feng Ding,Jie Ding,Jianmei Liu,Tulin Lu,Lihong Chen
Ethnopharmacological relevance Licorice is widely used clinically as one of the most famous traditional Chinese herbs. Its herb roasted with honey is called honey-processed licorice (HPL). Modern studies have shown that HPL has a stronger cardioprotective ability compared to raw licorice (RL), however the material basis and mechanism of action of the potential cardioprotection have not been fully elucidated. Aim of the study To screen and validate the material basis of cardioprotection exerted by HPL and to preliminarily predict the potential mechanism of action. Materials and methods UPLC-QTOF-MS/MS was used to analyze HPL samples with different processing levels, and differential compounds were screened out through principal component analysis. Network pharmacology and molecular docking were applied to explore the association between differential compounds and doxorubicin cardiomyopathy and their mechanisms of action were predicted. An in vitro model was established to verify the cardioprotective effects of differential compounds. Results Six differential compounds were screened as key components of HPL for potential cardioprotection. Based on network pharmacology, 113 potential important targets for the treatment of Dox-induced cardiotoxicity were screened. KEGG enrichment analysis predicted that the PI3K-Akt pathway was closely related to the mechanism of action of active ingredients. Molecular docking results showed that the six differential compounds all had good binding activity with Nrf2 protein. In addition, in vitro experiments had shown that five of the active ingredients (liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, and licochalcone A) can significantly increase Dox-induced H9c2 cell viability, SOD activity, and mitochondrial membrane potential, significantly reduces MDA levels and inhibits ROS generation. Conclusion Liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin and licochalcone A are key components of HPL with potential cardioprotective capabilities. Five active ingredients can alleviate Dox-induced cardiotoxicity by inhibiting oxidative stress and mitochondrial damage.
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ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Hui Li,Yuan Fan,Yizhe Shen,Huashan Xu,Huijie Zhang,Fuxue Chen,Shini Feng
The evolution of nano-drug delivery systems addresses the limitations of conventional cancer treatments with stimulus-responsive nanomaterial-based delivery systems presenting temporal and spatial advantages. Among various nanomaterials, boron nitride nanoparticles (BNNs) demonstrate significant potential in drug delivery and cancer treatment, providing a high drug loading capacity, multifunctionality, and low toxicity. However, the challenge lies in augmenting nanomaterial accumulation exclusively within tumors while preserving healthy tissues. To address this, we introduce a novel approach involving cancer cell membrane-functionalized BNNs (CM-BIDdT) for the codelivery of doxorubicin (Dox) and indocyanine green to treat homologous tumor. The cancer cell membrane biomimetic CM-BIDdT nanoparticles possess highly efficient homologous targeting capabilities toward tumor cells. The surface modification with acylated TAT peptides (dTAT) further enhances the nanoparticle intracellular accumulation. Consequently, CM-BIDdT nanoparticles, responsive to the acidic tumor microenvironment, hydrolyze amide bonds, activate the transmembrane penetrating function, and achieve precise targeting with substantial accumulation at the tumor site. Additionally, the photothermal effect of CM-BIDdT under laser irradiation not only kills cells through thermal ablation but also destroys the membrane on the surface of the nanoparticles, facilitating Dox release. Therefore, the fabricated CM-BIDdT nanoparticles orchestrate chemo–photothermal combination therapy and effectively inhibit tumor growth with minimal adverse effects, holding promise as a new modality for synergistic cancer treatment.
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Nanoscale
·
2015
·Vol. 8
·期 5
·3100-3118
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IF 7.394
Di Jiang,Xiaoling Gao,Ting Kang,Xingye Feng,Jianhui Yao,Mengshi Yang,Yixian Jing,Qianqian Zhu,Jingxian Feng,Jun Chen
Drug resistance is the major reason for therapeutic failure during cancer treatment. Chemo-photodynamic combination therapy has potential to improve the treatment efficiency in drug-resistant cancers, but is limited by the incompatible physical properties of the photosensitizer with a chemo-drug and poor accumulation of both drugs into the inner areas of the tumor. Herein, a novel drug delivery system was designed by incorporating the photosensitizer, chlorine 6, chemically in the shell and the chemo-drug, doxorubicin, physically in the core of D-α-tocopheryl polyethylene glycol 1000 succinate-poly(lactic acid) (TPGS-PLA) nanoparticles with a targeting ligand, tLyp-1 peptide, decorated over the surface (tLyp-1-NP). This nanoparticle with a high drug loading capacity of both the photosensitizer and chemo-drug is expected to realize chemo-photodynamic combination therapy of drug-resistant cancer and simultaneously achieve the specific deep penetration and accumulation of drugs into the inner areas of tumor. tLyp-1-NP was prepared via a nanoprecipitation method and it exhibited a uniformly spherical morphology with a size of approximately 130 nm. After appropriate irradiation, tLyp-1-NP showed high cellular uptake and strong cytotoxicity in both human umbilical vein endothelial cells (HUVEC cells) and doxorubicin-resistant human breast adenocarcinoma cells (MCF-7/ADR cells) in vitro. After intravenous administration, compared with the unmodified NPs, tLyp-1-NP was found to have superior tumor targeting ability and more potent reversion of doxorubicin-resistant cancer. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and the hematoxylin and eosin staining of the treated tumors further demonstrated the anti-tumor efficacy of tLyp-1-NP in the presence of a laser. These observations collectively suggest the potential of tLyp-1-NP for the actively targeting chemo-photodynamic combination therapy of drug-resistant cancer.
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RSC Advances
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2016
·Vol. 6
·期 56
·50993-51004
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IF 3.289
Beibei Lu,Lei Li,Lulu Wei,Xuhong Guo,Jun Hou,Zhiyong Liu
Well-defined amphiphilic β-cyclodextrin (β-CD) star-shaped copolymers with poly(ε-caprolactone)–poly(2-(2-methoxyethoxy)ethyl methacrylate)-co-poly(ethylene glycol)methacrylate) (β-CD–(PCL–P(MEO2MA-co-PEGMA))21 were synthesized via ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP). These thermo-responsive copolymers exhibited a lower critical solution temperature (LCST) in water, which could be finely tuned by changing the feed ratio of PEGMA and MEO2MA. The LCST of star-shaped β-CD–(PCL–P(MEO2MA-co-PEGMA))21 increased from 26 to 62 °C with the increasing PEGMA content, the copolymers were characterized using Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H NMR) and gel permeation chromatography (GPC). The star-shaped copolymers could self-assemble into micelles in aqueous solution due to their amphiphilic properties resulting from the hydrophobic β-CD and PCL core and the hydrophilic P(MEO2MA-co-PEGMA) segments, which was investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The in vitro DOX release studies showed that DOX released from drug-loaded micelles in a thermo-sensitive manner. CCK-8 assays demonstrated that these star-shaped copolymers could possess low cytotoxicity against HeLa cells, and the DOX-loaded micelles exhibited a higher inhibition of the proliferation of HeLa cells in comparison with free DOX. Moreover, the results from confocal laser scanning microscopy (CLSM) revealed that these polymeric micelles could efficiently deliver and release DOX into the nuclei of HeLa cells. This kind of biodegradable, biocompatible and stimuli-responsive copolymer could serve as a promising material for drug delivery.
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JOURNAL OF CHROMATOGRAPHY A
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2011
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IF 4.194
Shun Shen,Jinfeng Ren,Jun Chen,Xiaohui Lu,Chunhui Deng,Xinguo Jiang
For the first time, magnetic multiwalled carbon nanotubes (MWNTs) combined with near-infrared radiation-assisted desorption (NIRAD) was successfully developed for the determination of tissue distribution of doxorubicin liposome injects (DOXLI) in rats. The magnetic MWNTs nanomaterials were synthesized via a simple hydrothermal process. Magnetic Fe 3 O 4 beads, with average diameters of ca. 200 nm and narrow size distribution, were decorated along MWNTs to form octopus-like nanostructures. The hybrid nanocomposites provided an efficient way for the extraction and enrichment of doxorubicin (DOX) via π–π stacking of DOX molecules onto the polyaromatic surface of MWNTs. DOX adsorbed with magnetic MWNTs could be simply and rapidly isolated through a magnetic field . In addition, due to the near-infrared radiation (NIR) absorption property of MWNTs, irradiation with NIR laser was employed to induce photothermal conversion, which could trigger rapid DOX desorption from DOX-loaded magnetic MWNTs. Extraction conditions such as amount of magnetic MWNTs added, pH values, adsorption time, desorption solvent and NIR time were investigated and optimized. Method validations including linear range, detection limit, precision, and recovery were also studied. The results showed that the proposed method based on magnetic MWNTs coupled to NIRAD was a simple, rapid and high efficient approach for the analysis of DOXLI in rat tissues.
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ACS Applied Materials & Interfaces
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2026
·
IF 7.8
Xiaomeng Zou,Shiyu Li,Zhiying Jin,Sisi Huang,Ruilan Niu,Naiqin Fu,Wenqing Li,Jianbo Gao,Zhili Wang
Immunogenic cell death (ICD) represents a promising strategy to stimulate antitumor immunity. Doxorubicin (DOX) is one drug that can trigger ICD. However, DOX has limitations for treating triple-negative breast cancer (TNBC). Its ability to stimulate a strong immune response is weak. The drug also promotes an immunosuppressive tumor microenvironment. This suppression hinders the antitumor immune response. Since reactive oxygen species (ROS) generation is a pivotal ICD trigger, we therefore hypothesized that nintedanib, a triple tyrosine kinase inhibitor known to promote immune cell infiltration and activation within tumors, potentiates DOX-induced ICD by augmenting intratumoral ROS generation. To address this, we engineered a targeted nanoenhancer for TNBC by coencapsulating liquid nintedanib and perfluoropentane (PFP), within a peptide-functionalized (tLyp-1) liposomal shell, creating tLyp-1-Nintedanib-PFP Nanoparticles (tNP-NPs) for use in sonodynamic therapy. This tNP-NP platform is intended for combination therapy with DOX in a chemoimmunotherapeutic strategy. With the assistance of low-intensity focused ultrasound (LIFU), tNP-NPs exhibited potent targeting and penetrating capabilities toward 4T1 TNBC cells, enhanced drug cytotoxicity, ROS production, and ICD markers in vitro. Subsequently, for the in vivo study, to mitigate systemic toxicity, an injectable thermosensitive hydrogel coencapsulating tNP-NPs and DOX was applied for local peritumoral injection. In orthotopic 4T1 TNBC models, this combination elicited potent ICD, promoting dendritic cell (DC) cells maturation and cytotoxic T lymphocyte activation within tumors and draining lymph nodes. This approach achieved exceptional antitumor efficacy and systemic immunity while reversing the immunosuppressive tumor microenvironment, without observable organ toxicity, presenting a robust chemoimmunotherapeutic strategy for TNBC.
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International Journal of Nanomedicine
·
2026
·
IF 8.7
Zhibo Gu,Hua Zhu,Yong Zhang,Jie Jiang,Donghua Gu,Jiangang Chen
Objective This study developed a multifunctional MnFe2O4/TiVNbMoC3-cRGD (MXenes) nanocomposite for targeted photothermal- photodynamic therapy against bladder cancer.Methods A multifunctional MXene-based nanocomposite was constructed by integrating MnFe2O4 nanoparticles onto TiVNbMoC3 MXene nanosheets to form a layer-on-layer Schottky junction, followed by conjugation of cRGD peptides for tumor targeting. Successful synthesis, colloidal stability, broad optical absorption, efficient photothermal conversion and ROS generation under 808 nm laser were confirmed. In vitro assays were conducted using 5637 bladder cancer cells, and a murine bladder tumor model was established to evaluate the anticancer efficacy. Biocompatibility assessments were also carried out.Results The composite was constructed by integrating MnFe2O4 nanoparticles onto TiVNbMoC3 MXene nanosheets, which formed a layer - on - layer Schottky junction. Then, cRGD peptides were conjugated to the surface for tumor targeting. Comprehensive characterization confirmed successful synthesis, favorable colloidal stability, broad optical absorption, and efficient photothermal conversion and reactive oxygen species (ROS) generation under 808 nm laser irradiation. In vitro, the cRGD-targeted nanocomposite was efficiently internalized by 5637 bladder cancer cells and showed significantly higher anticancer efficacy than doxorubicin (DOX), including inhibition of proliferation, migration, colony formation, and induction of apoptosis and immunogenic cell death. In a murine bladder tumor model, the nanocomposite achieved the strongest tumor growth suppression and reduced final tumor volume more effectively than DOX. Biocompatibility assessments showed minimal hemolysis and no major organ damage at therapeutic doses.Conclusion This MXene-based Schottky junction nanocomposite represents a promising targeted platform for dual-modal photothermal/photodynamic therapy combined with immune activation in bladder cancer, warranting further translational investigation.
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BIOPHARMACEUTICS & DRUG DISPOSITION
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2026
·
IF 2.2
Xue-ting Huang,Jing-jing Liu,Xi-yang Tang,Guo Yin,Yi Dai,Xiao-wei Wang
Doxorubicin hydrochloride liposome injection represents a complex nano-drug delivery system with significant clinical advantages, yet its quality evaluation remains challenging. Traditional static release methods often fail to simulate the physiological environment, which leads to poor in vivo predictions. The flow-through cell method provides distinct advantages by simulating hemodynamic characteristics and maintaining stable sink conditions. This study utilizes the flow-through cell method to simulate the release process of doxorubicin hydrochloride liposomes and establishes a Level A in vitro-in vivo correlation (IVIVC) based on the in vivo data of three commercial brands to develop a biorelevant in vitro release method. The in vivo cumulative release fraction is derived from the plasma concentration data of three commercial products using the fractional area (AUC) method for deconvolution, which serves as the target reference for the in vitro release profile. In vitro release experiments are conducted using a phosphate buffer containing 0.3% SDS and 15% artificial plasma as the release medium, which is optimized through single-factor analysis and an L 9 (3 4 ) orthogonal experimental design. The experimental setup employs a dialysis membrane with a 300 KDa molecular weight cutoff and a flow rate of 4 mL/min. High-performance liquid chromatography (HPLC) determines the concentration of the released drug to calculate the in vitro cumulative release fraction. A Level A IVIVC model is established between the cumulative in vitro and in vivo release fractions of doxorubicin hydrochloride liposome injection, which is subsequently confirmed through internal validation. The IVIVC model demonstrates robust predictive capability, and the developed in vitro release method exhibits high sensitivity in distinguishing the release characteristics of products from different manufacturers. This study provides a scientific reference for the in vitro-in vivo correlation and quality evaluation of long-acting injections.
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