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Micro & Nano Letters · 2019 ·Vol. 14 ·期 5 ·520-525 · IF 0.975

Magnetic/pH dual-responsive nanocomposites loading doxorubicin hydrochloride for cancer therapy

Tingting Zhang,Kun Zhang,Feng Jiang,Jianfeng Zhang,Xin Song,Jinshun Zhao

Development of stimuli-responsive nanocomposites for the delivery anticancer drug has attracted considerable attention. A magnetic/pH dual-responsive nanocomposite was synthesised by amide condensation reaction and developed for cancer therapy. The PEGylated citric-coated Fe 3 O 4 (PCI)–graphene oxide (GO) nanocomposites was constructed by a three-step process. Fe 3 O 4 magnetic nanoparticles were firstly coated with citric acid, and then covalently linked to aminated polyethylene glycol (NH 2 –PEG–NH 2 ); lastly, the PCI was covalently conjugated to graphite oxide to obtain PCI–GO nanocomposites. The PCI–GO nanocomposites were characterised by X-ray diffraction, scanning electron microscopy, Fourier transform-infrared, ultraviolet–visible, and thermogravimetry. The magnetic of nanocomposites was confirmed by a vibrating sample magnetometer. Due to the hydrogen bond, π – π stacking and electrostatic interaction between the doxorubicin (DOX) hydrochloride and PCI–GO nanocomposites, the PCI–GO nanocomposites could load DOX effectively and with a high drug loading content (about 87.6%). The DOX-loaded PCI–GO (DOX/PCI–GO) nanocomposites exhibited pH-responsive release behaviour. The DOX/PCI–GO nanocomposites could effectively inhibit tumour growth in vitro, which was comparable to the antitumour effect of free DOX. The result indicates that the PCI–GO nanocomposites exhibit great potential for a magnetic targeted drug delivery system in multimodal and synergistic cancer therapy.

研究领域: 纳米技术 · 癌症研究 · 材料科学 · 药剂学
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ACS Applied Bio Materials · 2020 · IF 0

Preparation, Characterization, and Release Behavior of Doxorubicin hydrochloride from Dual Cross-Linked Chitosan/Alginate Hydrogel Beads

Ting Wu,Shaobin Yu,Dongzi Lin,Zhimin Wu,Jun Xu,Jinglin Zhang,Zefen Ding,Ying Miao,Tao Liu,Tao Chen,Xiang Cai

With double cross-linking of chitosan (CS) and sodium alginate (SALG), a colon-targeting CS/SALG hydrogel bead was prepared and used for the colon-targeted release of doxorubicin hydrochloride (DOX). The CS/SALG hydrogel bead showed the improved mechanical property to withstand the simulated colon intestinal fluid (SCF), small intestinal fluid (SIF), as well as gastric fluid (SGF). DOX was released slightly in SGF and SIF and rapidly in SCF, showing a controlled DOX release from the CS/SALG hydrogel bead under different physiological conditions. In vitro cytotoxicity and in vivo toxicity assays indicated that the DOX-loaded CS/SALG hydrogel bead displayed obvious inhibition to tumor cells. These results suggested that the CS/SALG hydrogel bead had the potential application as a colon-targeting oral formulation for DOX transport.

研究领域: 药物学 · 材料科学 · 药物递送系统
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2016 · IF 3.902

Alternate release of different target species based on the same gold nanorods and monitored by cell imaging

Shenna Chen,Haowen Huang,Lingyang Zhang,Yun Chen,Xuanyong Liu

In this study, a strategy for load and release of different kinds of molecules on the same gold nanorods (GNRs) was developed. An anticancer drug, doxorubicin hydrochloride (DOX), was firstly chemically conjugated on the GNRs. To efficiently load another type of target molecules DNA on the same GNRs, a polyelectrolyte Poly (ethylene imine) (PEI) was adsorbed on the [email protected] to form [email protected] @PEI. Then, the positive charge [email protected] @PEI allows the GNR conjugates to interact with negative charged DNA by an electrostatic interaction, enabling their full conjugation. A platform to load two kinds of target molecules conjugated on the same GNRs was fabricated. On the other hand, selective and sequential release of the different target species may be triggered by chemical reaction and near infrared (NIR) laser. The release of DOX was achieved by Na 2 S 2 O 3 reacting with GNRs and the discharge of DNA conjugated on the [email protected] @PEI was accomplished by local-heating using NIR laser triggered release. Furthermore, the selective and alternate release of different target species from the GNRs inside MCF-7 cells was monitored by fluorescent imaging, providing a potential synergistic cancer treatment.

研究领域: 纳米技术 · 癌症研究 · 生物医学工程 · 分子生物学
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FOOD HYDROCOLLOIDS · 2018 · IF 5.089

Preparation and characterization of pectin/chitosan beads containing porous starch embedded with doxorubicin hydrochloride: A novel and simple colon targeted drug delivery system

Jianzhong Zhu,Li Zhong,Wenxue Chen,Yizhe Song,Zhengming Qian,Xianying Cao,Qiang Huang,Bin Zhang,Haiming Chen,Weijun Chen

The objective of this study was to design a simple, colon targeted drug delivery system by using porous starch (PS), pectin and chitosan. Porous maize starch was prepared by hydrolysis with a combination of α-amylase and amyloglucosidase, and it was characterized by scanning electron microscopy, revealing the formation of porous structures in the starch granules. A Brunauer-Emmett-Teller (BET) specific surface area analysis indicated that the specific surface area of the PS (0.8768–0.9448 m 2 /g) was 19.88–21.42 times larger than that of native maize starch (0.0441 m 2 /g). The average pore diameter of the PS granules, as calculated by the Barrett-Joiner-Halenda (BJH) method, was 40.52–62.42 nm. A favorable adsorptive potential of the PS granules was verified by water and soybean oil tests. Doxorubicin was loaded into PS granules, which were then coated with a pectin/chitosan complex solution. The results of confocal laser scanning microscopy (CLSM) demonstrated that doxorubicin was successfully absorbed into the PS granules. In addition, an in vitro simulated digestion method demonstrated the effectiveness of this delivery design, as only a 13.80% release rate of doxorubicin was observed in the upper gastrointestinal tract, whereas release rates of 17.56% and 67.04% were observed for pectin/PS/doxorubicin and pectin/doxorubicin beads, respectively. It was concluded that the use of PS and a pectin/chitosan coating is an effective method for colon targeted drug delivery compared with the simple polysaccharide system.

研究领域: 药学 · 材料科学 · 生物技术
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Nanomaterials · 2019 ·Vol. 9 ·期 2 ·188 · IF 4.034

Preparation of Targeted Lignin–Based Hollow Nanoparticles for the Delivery of Doxorubicin

Yu Zhou,Yanming Han,Gaiyun Li,Sheng Yang,Fuquan Xiong,Fuxiang Chu

Due to their exceptional absorption capacity, biodegradability, and non-toxicity, nanoparticles (NPs) from lignin have emerged as vehicles for inorganic particles and drug molecules. However, the method for preparing targeted lignin particles is still complex and lacks sufficient research. Herein, a succinct strategy was proposed for the preparation of targeted lignin-based drug delivery NPs to load Doxorubicin Hydrochloride (DOX). The lignin hollow NPs (LHNPs) were used as a platform for the preparation of targeted delivery material by incorporating magnetic NPs and folic acid (FA) via layer-by-layer self-assembling. The results showed that the surface of LHNPs was covered uniformly by Fe3O4NPs and grafted with folic acid. The folic-magnetic-functionalized lignin hollow NPs (FA-MLHNPs) could respond to magnetic field and folic acid receptors. In addition, the targeting performance of the FA-MLHNPs increased the cellular uptake of NPs in the case of HeLa cells. This research not only supported the modified NPs platform as a highly efficient nano-delivery method but also provided a facile approach to utilize renewable lignin biomaterials.Keywords:lignin;nanoparticles;targeted materials;drug delivery

CAS / MDL: 26062-79-3
研究领域: 药学 · 材料科学 · 生物技术 · 纳米技术
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JOURNAL OF NANOBIOTECHNOLOGY · 2021 ·Vol. 19 ·期 1 ·1-14 · IF 10.435

Au-siRNA@ aptamer nanocages as a high-efficiency drug and gene delivery system for targeted lung cancer therapy

Yang Yuming,Han Yu,Sun Qiuyang,Cheng Jin,Yue Caixia,Liu Yanlei,Song Jie,Jin Weilin,Ding Xianting,de la Fuente Jesús M.,Ni Jian,Wang Xiaoqiang,Cui Daxiang

Background Gene and chemical therapy has become one of the rising stars in the field of molecular medicine during the last two decades. However, there are still numerous challenges in the development of efficient, targeted, and safe delivery systems that can avoid siRNA degradation and reduce the toxicity and adverse effects of chemotherapy medicine.Results In this paper, a highly efficient AS1411 aptamer modified, dsDNA and MMP-2 cleavable peptide-fabricated gold nanocage vehicle, which could load doxorubicin hydrochloride (DOX) and siRNAs to achieve a combination of tumor responsive genetic therapy, chemotherapy, and photothermal treatment is presented. Our results show that this combined treatment achieved targeted gene silencing and tumor inhibition. After nearly one month of treatment with DOX-loaded Au-siRNA-PAA-AS1411 nanoparticles with one dose every three days in mice, a synergistic effect promoting the eradication of long-lived tumors was observed along with an increased survival rate of mice. The combined genetic, chemotherapeutic, and photothermal treatment group exhibited more than 90% tumor inhibition ratio (tumor signal) and a ~ 67% survival rate compared with a 30% tumor inhibition ratio and a 0% survival rate in the passive genetic treatment group.Conclusion sThe development of nanocarriers with double-stranded DNA and MMP-2 cleavable peptides provides a new strategy for the combined delivery of gene and chemotherapy medicine. Au-siRNA-PAA-AS1411 exerts high anticancer activities on lung cancer, indicating immense potentials for clinical application.

研究领域: 纳米技术 · 肿瘤学 · 药学 · 分子医学
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Nanoscale · 2020 ·Vol. 12 ·期 36 ·18682-18691 · IF 6.895

A facile and efficient approach for hypertrophic scar therapy via DNA-based transdermal drug delivery

Kai Jiang,Yunsheng Chen,Di Zhao,Jin Cheng,Fangli Mo,Bin Ji,Chao Gao,Chuan Zhang,Jie Song

The transdermal drug delivery approach has been considered a potential therapy for human hypertrophic scars (HSs) instead of current uncomfortable surgical excision, local injection and laser therapy. However, a facile and efficient drug delivery method is urgently needed to overcome the skin barrier of transdermal administration. Herein, we employed a DNA-Fe nanoparticle delivery system via Fe ion driven self-assembly to satisfy the requirement of transdermal administration for HS therapy. Doxorubicin hydrochloride (DOX) as one of the widely used anticancer drugs was employed to treat the hyperplasia of abnormal skin fibrous tissue. Both in vitro and in vivo experiments of the DOX loaded DNA-Fe nanoparticles (DOX@DNA-Fe NPs) were performed to demonstrate the penetration ability, rapid drug release, and scar-inhibiting effects. This facile and efficient approach for HS therapy via a DNA-based transdermal drug delivery system may provide more possibilities for the development of transdermal administration.

研究领域: 药学 · 纳米技术 · 皮肤病学
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Journal of Materials Chemistry B · 2023 ·Vol. 11 ·期 24 ·5406-5415 · IF 7

A photocatalytic carbon monoxide-generating effervescent microneedle patch for improved transdermal chemotherapy

Junzhe Fu,Weijiang Yu,Xuedan Qian,Youxiang Wang,Jian Ji

Carbon monoxide (CO) is regarded as a promising therapeutic agent for chemotherapy sensitization. To simultaneously achieve controllable in situ CO production and efficient chemotherapeutics delivery is of great significance. Here, we presented a polyvinylpyrrolidone (PVP) core–shell microneedle (MN) system that encapsulated the effervescent component, photocatalyst, and doxorubicin hydrochloride (Dox·HCl) for CO-sensitized chemotherapy. Upon the insertion of MNs, the effervescent component, composed of sodium bicarbonate and tartaric acid, was exposed to interstitial fluid, leading to the burst release of carbon dioxide (CO2). The generated gas not only enhanced the diffusion of Dox·HCl but also served as a substrate for the photocatalytic generation of CO. From the experimental results, the photocatalyst CuS atomic layers (CAL) displayed an effective CO2 photoreduction performance, which could realize an irradiation time/intensity-dependent CO-controlled release. Ex vivo permeation studies demonstrated that effervescent CO2 production markedly enhanced the intradermal diffusion of Dox·HCl. Eventually, the robust antitumor efficacy of this versatile MN platform was proved in B16F10-bearing nude mice. This CO-sensitized chemotherapeutic MN system offered a novel strategy for transdermal gas/drug delivery, which might provide a new direction in tumor suppression.

研究领域: 药学 · 生物医学工程 · 癌症治疗
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CARBOHYDRATE POLYMERS · 2017 · IF 4.811

Engineering pectin-based hollow nanocapsules for delivery of anticancer drug

Feng Ji,Junjie Li,Zhihui Qin,Boguang Yang,Ershuai Zhang,Dianyu Dong,Jinmei Wang,Yan Wen,Liang Tian,Fanglian Yao

Multifunctional capsules have great applications in biomedical fields. In this study, novel polysaccharide-based nanocapsules were prepared via a layer-by-layer technique using silica as the templates. The shell was constructed based on the electrostatic interactions between pectin and chitosan. The pectin-chitosan nanocapsules ((Pec/Cs) 3 Pec) could keep good colloidal stability within 96   h in PBS solution and 48   h in BSA solution. Meanwhile, the nanocapsules exhibited a high drug loading and pH-sensitive release property for doxorubicin hydrochloride. Moreover, (Pec/Cs) 3 Pec nanocapsules had no cytotoxicity to both human hepatocellular carcinoma cells (HepG2 cells) and mouse fibroblast cells (L929 cells). More importantly, (Pec/Cs) 3 Pec nanocapsules could be more easily uptaken by HepG2 cells when compared with L929 cells. In vitro anticancer activity tests indicated the carriers could effectively kill HepG2 cells. Overall, (Pec/Cs) 3 Pec nanocapsules have great potential as a novel anticancer drug carrier as a result of their pH-sensitivity, good colloidal stability and anticancer activity.

CAS / MDL: 3326-32-7 7664-39-3
研究领域: 生物医学工程 · 药剂学 · 纳米技术 · 癌症研究
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Materials Today Chemistry · 2022 · IF 7.613

Industrially synthesized biosafe vaterite hollow CaCO3 for controllable delivery of anticancer drugs

Zongqi Feng,Tingyu Yang,Shichao Dong,Ting Wu,Wen Jin,Zhouying Wu,Bingping Wang,Tiantian Liang,Lei Cao,Lan Yu

Calcium carbonate (CaCO 3 ) has been widely studied as a drug delivery system (DDS), but it still has some limitations in its clinical application in tumor chemotherapy, such as difficult industrialization, complex synthesis methods, time-consuming and labor-intensive, and low drug loading. Here, we developed an industrialized method for the simple, rapid and controllable synthesis of high drug-loaded vaterite hollow CaCO 3 (VHC). The VHC was successfully prepared by adding L-Leucine (Leu) in the process of preparing CaCO 3 in an industrial method. The effects of different reaction conditions on VHC were studied in detail, and a possible formation mechanism of VHC was proposed. As an industrially synthesized DDS, the VHC had low cytotoxicity and good biocompatibility, and had higher loading capacity (39.68%) and encapsulation efficiency (90.17%) for doxorubicin hydrochloride (DOX) due to the existence of hollow nano-cavity. Meanwhile, DOX@VHC showed good pH responsiveness, which can achieve sustained release of DOX. And, DOX@VHC could significantly inhibit tumor cells (cell inhibitory rate: 91.73%) and reduce the toxicity to normal cells. The high drug-loaded VHC synthesized rapidly by industrial methods can achieve controllable drug delivery and high-efficiency inhibition of tumor cells, and has a good application prospect in tumor therapy.

CAS / MDL: 25316-40-9 61-90-5
研究领域: 药学 · 材料科学 · 生物医学工程 · 肿瘤学
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2023 · IF 5.8

Injectable rhein-assisted crosslinked hydrogel for efficient local osteosarcoma chemotherapy

Lei Zhang,Ying-Xuan Liu,Ya-Ting Yao,Tian-Jiao Zhou,Hu-Lin Jiang,Cheng-jun Li

Osteosarcoma (OS) is the most common malignant tumor of the bone that affects children and adolescents, and its treatment usually involves doxorubicin hydrochloride (DOX). However, the drug resistance and side effects caused by high-dose DOX infusion greatly hinder its therapeutic effects. To achieve efficient OS treatment with low toxicity, an injectable rhein (RH)-assisted crosslinked hydrogel ( [email protected] @DOX hydrogel, PRDH) was designed, which was prepared by loading DOX and RH into a polyvinyl alcohol (PVA) solution. The cytotoxicity assay and live/dead staining results showed that the combination of RH and DOX more effectively killed OS cells, producing excellent effects at low concentrations of DOX. The wound healing and transwell test results proved that PRDH could significantly inhibit the metastasis and invasion of OS cells. PRDH showed a long-lasting antitumor effect after injection of a single dose, significantly suppressing the proliferation and metastasis of OS and achieving the strategy of a single administration for long-term treatment. Excitingly, RH facilitated hydrogel formation by assisting with PVA crosslinking. This system provides an alternative regimen and broadens the horizon for the clinical treatment of OS.

CAS / MDL: 25316-40-9 478-43-3
研究领域: 药学 · 肿瘤学 · 材料科学
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Materials Today Communications · 2024 · IF 3.7

Simulation of in vitro embolization effect of drug-loaded microspheres

Lan Zhang,Baoqu Zhang,Rongkang Yu,Shuyue Wu,Shugao Han,Rui Tang,Ruibo Zhao,Xiangdong Kong

Drug-loaded microspheres are widely used in transcatheter arterial chemoembolization (TACE). Controlled drug release from drug-loaded microspheres reduces systemic toxicity, thus necessitating the development of microspheres with controlled release properties. In this study, three different sizes of sodium hyaluronate microspheres (SH) were prepared by a one-step solution drying method using 1,4-butanediol diglycidyl ether (BDDE) as a crosslinking agent. The average sizes of the three SH microspheres (small, medium and large) were 410 μm, 550 μm and 750 μm, respectively. The morphology of the small-sized SH microspheres (SS-SH) was solid spherical; the medium-sized SH microspheres (MS-SH) were semi-hollow spherical; and the large-sized SH microspheres (LS-SH) had a bowl with an opening on one side and a cavity inside. A drug-loaded microsphere (DOX@SH) was prepared by immersing SH microspheres in a doxorubicin hydrochloride (DOX) solution. The average size of the three DOX@SH microspheres increased to 607 μm, 876 μm and 1187 μm, respectively. The encapsulation efficiencies of small, medium and large-sized SH microspheres reached 97.09 %, 96.73 % and 74.87 % at 2 h in a 2 mg/mL DOX solution. The maximum drug loadings of the small, medium and large-sized SH microspheres were 0.38, 0.38 and 0.33 mg DOX/mg SH, respectively. All sizes of DOX@SH microspheres could be controlled and sustained to release and reach equilibrium after 48 h. The cumulative release rates of small, medium and large-sized DOX@SH microspheres (SS-DOX@SH, MS-DOX@SH and LS-DOX@SH) at 72 h were 24.3 %, 28.1 % and 33.8 % in a release medium of pH 6.5, respectively. Blood compatibility and cytotoxicity tests demonstrated that SH microspheres exhibit good biocompatibility. The cytotoxicity of DOX@SH microspheres to HepG2 cells and the uptake of DOX in HepG2 cells showed effective anti-tumor activity. Simulated embolization in vitro experiments indicated that the small-sized DOX@SH microspheres had a good embolization effect for 500–800 μm and 300–500 μm blood vessels. These findings indicate that the newly developed DOX@SH microspheres can be used as a promising drug-loaded embolization agent to enhance the treatment of hepatocellular carcinoma.

研究领域: 药学 · 生物医学工程 · 肿瘤学
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