CARBOHYDRATE POLYMERS
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2022
·
IF 10.723
Jun Wang,Justin Liu,Dao-Qiang Lu,Lijing Chen,Rujia Yang,Dahai Liu,Bin Zhang
In this paper, we report a simple approach to fabricate diselenide-crosslinked carboxymethyl chitosan nanoparticles (DSe-CMC NPs) for doxorubicin (DOX) delivery, with disulfide analogs (DS-CMC NPs) as control. DS-CMC NPs and DSe-CMC NPs featured a spherical morphology and narrow size distribution with the average size about 200 nm. Carboxymethyl chitosan (CMC) as the starting material not only improved the biocompatibility of the nanocarriers but also enhanced physiological stability. Due to electrostatic interactions between DOX and CMC, the nanoparticles had high drug encapsulation efficiency (∼25 %). The nanoparticles disintegration and drug release were accelerated by the cleavage of diselenide bonds through oxidation by H 2 O 2 or reduction by GSH. In vitro cell experiments revealed that DOX-loaded DSe-CMC NPs possessed the highest drug accumulation and cytotoxicity in tumor cells. Moreover, DOX-loaded DSe-CMC NPs performed the enhanced growth inhibition in vivo than that of DS-CMC NPs. Thus, the diselenide-crosslinked nanoparticles possess great potentials for DOX delivery.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2022
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IF 6.51
Jinfeng He,Shuqian Yu,Ziyi Ma,Haotian Sun,Qinghua Yang,Zhiwei Liu,Xuan Wang,Xiaoyu Zhang,Longgang Wang
Gold nanoparticles are a kind of good photothermal agents. However, gold nanoparticle photothermal agents have low photothermal conversion efficiency and low tumor inhibiting ability. To overcome these problems, polymyxin E (PE) biomineralized and doxorubicin-loaded gold nanoflowers (DOX-SH@AuNFs) nanodrug was synthesized by the green synthesis method using the biological antimicrobial peptide PE as a stabilizer and grower of crystal seed, and doxorubicin-thiol (DOX-SH) was further loaded on the gold nanoparticles through the Au-S bond. The final DOX-SH@AuNFs displayed a wide absorption band in the UV–Vis spectra, and their photothermal conversion efficiency was 33.9%. Furthermore, the inhibition rate of DOX-SH@AuNFs on A549 cells was as high as 80.1% under the irradiation of near-infrared light at 808 nm. The tumor inhibition rate of DOX-SH@AuNFs was as high as 87.81% in vivo experiments. The high tumor suppression rate was attributed to the high photothermal conversion ability of DOX-SH@AuNFs and the delivery of doxorubicin. Taken together, the method of preparing DOX-SH@AuNFs provides a new idea for the treatment of cancer by photothermal therapy and chemotherapy synergistic system.
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CHINESE JOURNAL OF POLYMER SCIENCE
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2022
·Vol. 41
·期 4
·525-537
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IF 3.815
Zhou Meng-Xue,Zhang Jia-Yu,Cai Xiao-Meng,Dou Rui,Ruan Li-Fo,Yang Wen-Jiang,Lin Wen-Chu,Chen Jun,Hu Yi
As one of the major challenges in tumor chemotherapy, multidrug resistance typically correlates with the poor drug penetration within tumor tissues and drug efflux by the ATP-driven efflux pumps in tumor cells. Herein, we design a kind of near-infrared (NIR) light- and acidity-activated micellar iPUTDN nanoparticle for mitochondria-targeting doxorubicin (DOX) delivery to combat DOX resistance in small-cell lung cancer. While the PEGylated iPUTDN nanoparticles can keep stealth in blood circulation, NIR irradiation at the tumor region can peel off the PEG shell from the nanoparticles, and the exposed iRGD can facilitate deep tumor penetration of the nanoparticles. After being internalized by DOX-resistant H69AR cells, the poly(β-aminoester)s (PAE)-based nanoparticles can release the triphenylphosphonium (TPP)-conjugated DOX (TDOX) into the cytosol, which can further accumulate in mitochondria with the aid of TPP. Consequently, the mitochondrial membrane potential and ATP content are both reduced in DOX-resistant H69AR cells. The in vivo therapeutic results show that TDOX-loaded nanoparticles with the aid of NIR light irradiation can effectively suppress the DOX-resistant small-cell lung cancer without noticeable adverse effects.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2022
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IF 5.518
Yaling Ye,Longwei Yin,Gary Owens,Zuliang Chen
Controlling the slow release of drugs in carriers and reducing environmental pollution and damage from antibiotics is important and challenging research. In this paper, a novel composite material of carbonized FeNPs@ZIF-8 (C-Fe 3 O 4 @ZIF-8) was used to load and release doxorubicin hydrochloride (DOX). Compared with conventional ZIFs materials, greatly enhancing the magnetic properties , drug loading capacity and controlled drug release of the carrier agent. Interestingly, by establishing a dual stimulus response system with environmental factors of pH and temperature, results showed release rate of 61.6 % at a pH of 3 and a temperature of 37 °C. In addition, the SEM-EDS results showed that the surface of C-Fe 3 O 4 @ZIF-8 was partially broken but maintained a stable morphology before and after release. Meanwhile the nitrogen absorption desorption curve (BET) and hysteresis loop reveal that C-Fe 3 O 4 @ZIF-8 can maintain a large specific surface area and a magnetization intensity of 12.4 emu g −1 after release. X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR), on the other hand, reveal the presence of partial ligand and hydrogen bond breaks during the release of DOX from DOX-loaded C-Fe 3 O 4 @ZIF-8. Finally, the release of DOX from C-Fe 3 O 4 @ZIF-8 at different pH and temperature is consistent with the Higuch and Bhaskas models, where the latter dominates and proposes a release mechanism. Therefore, the magnetic composite C-Fe 3 O 4 @ZIF-8 in this study has great potential for DOX to effectively control drug release and targeted cancer therapy.
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Nanomedicine
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2021
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IF 5.307
Chaoqi Li,Xiangbo Gou,Hui Gao
Aim: The authors aimed to develop Dox@Rg1 nanoparticles with decreased cardiotoxicity to expand their application in cancer. Materials & methods: Dox@Rg1 nanoparticles were developed by encapsulating doxorubicin (Dox) in a self-assembled Rg1. The antitumor effect of the nanoparticles was estimated using 4T1 tumor-bearing mice and the protective effect on the heart was investigated in vitro and in vivo. Results: Different from Dox, the Dox@Rg1 nanoparticles induced increased cytotoxicity to tumor cells, which was decreased in cardiomyocytes by the inhibition of apoptosis. The study in vivo revealed that the Dox@Rg1 nanoparticles presented a perfect tumor-targeting ability and improved antitumor effects. Conclusion: Dox@Rg1 nanoparticles could enhance the antitumor effects and decrease the cardiotoxicity of Dox.Lay abstractDoxorubicin (Dox) is a drug used to treat cancer; however, it can be toxic to the heart. In this study, researchers made nanoparticles containing Dox and a component of ginseng, a root similar to ginger. They tested the nanoparticles in mice with tumors. The nanoparticles appeared to gather at the tumor site in greater amounts than free Dox. In healthy mice, the nanoparticles gathered less in the heart than free Dox. This means that putting Dox into nanoparticles such as these could improve their anticancer effect and decrease harm to the heart.Graphical abstract
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JOURNAL OF NANOBIOTECHNOLOGY
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2021
·Vol. 19
·期 1
·1-16
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IF 10.435
Xu Jiangkang,Yang Xiaoye,Ji Jianbo,Gao Yuan,Qiu Na,Xi Yanwei,Liu Anchang,Zhai Guangxi
Background Glioblastoma is a lethal neoplasm with few effective therapy options. As a mainstay in the current treatment of glioma at present, chemotherapeutic agents usually show inadequate therapeutic efficiency due to their low blood brain barrier traversal and brain targeting, together with tumor multidrug resistance. Novel treatment strategies are thus urgently needed to improve chemotherapy outcomes. Results Here, we report that nanomedicines developed by functionalizing the neurotropic rabies virus-derived polypeptide, RVG, and loading reduction-sensitive nanomicelles (polymer and doxorubicin) enable a highly specific and efficacious drug accumulation in the brain. Interestingly, curcumin serves as the hydrophobic core of the polymer, while suppressing the major efflux proteins in doxorubicin-resistant glioma cells. Studies on doxorubicin-resistant rat glioma cells demonstrate that the RVG-modified micelles exhibit superior cell entry and antitumor activity. In vivo research further showed that RVG modified nanomicelles significantly enhanced brain accumulation and tumor inhibition rate in mice, leading to a higher survival rate with negligible systemic toxicity. Moreover, effective suppression of recurrence and pulmonary metastatic nodules were also determined after the RVG-modified nanomicelles treatment. Conclusions The potential of RVG-modified nanomicelles for glioma was demonstrated. Brain accumulation was markedly enhanced after intravenous administration. This unique drug delivery nanoplatform to the brain provides a novel and powerful therapeutic strategy for the treatment of central nervous system disorders including glioma. Graphic abstract
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Asian Journal of Pharmaceutical Sciences
·
2021
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IF 6.598
Yinxian Yang,Shiyi Zuo,Linxiao Li,Xiao Kuang,Jinbo Li,Bingjun Sun,Shujun Wang,Zhonggui He,Jin Sun
Ferroptosis is a new mode of cell death, which can be induced by Fenton reaction-mediated lipid peroxidation. However, the insufficient H 2 O 2 and high GSH in tumor cells restrict the efficiency of Fenton reaction-dependent ferroptosis. Herein, a self-supplying lipid peroxide nanoreactor was developed to co-delivery of doxorubicin (DOX), iron and unsaturated lipid for efficient ferroptosis. By leveraging the coordination effect between DOX and Fe 3+ , trisulfide bond-bridged DOX dimeric prodrug was actively loaded into the core of the unsaturated lipids-rich liposome via iron ion gradient method. First, Fe 3+ could react with the overexpressed GSH in tumor cells, inducing the GSH depletion and Fe 2+ generation. Second, the cleavage of trisulfide bond could also consume GSH, and the released DOX induces the generation of H 2 O 2, which would react with the generated Fe 2+ in step one to induce efficient Fenton reaction-dependent ferroptosis. Third, the formed Fe 3+ /Fe 2+ couple could directly catalyze peroxidation of unsaturated lipids to boost Fenton reaction-independent ferroptosis. This iron-prodrug liposome nanoreactor precisely programs multimodal ferroptosis by integrating GSH depletion, ROS generation and lipid peroxidation, providing new sights for efficient cancer therapy.
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JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS
·
2020
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IF 2.717
Lihua He,Rong Zheng,Jie Min,Fulin Lu,Changqiang Wu,Yunfei Zhi,Shaoyun Shan,Hongying Su
Hydrogel nanocomposites incorporated with magnetic nanoparticles (MNPs) were widely researched as promising candidate for environment-responsive drug delivery, due to their unique magnetic properties and quick response to an external magnetic field. In this study, dextran-coated iron oxide nanoparticles (Fe 3 O 4 ) with various particle size were prepared and embedded physically into dextran microgels formed via Schiff base reactions between aldehyded dextran and diamine in W/O inverse microemulsion, leading to a series of magnetic microgels with MNPs content of 3, 6, 9% by weight percentage. Similar superparamagnetic properties of as prepared microgels with Fe 3 O 4 nanoparticles were proved, and their saturation magnetization increased with the increasing particle size or content of the MNPs. Antitumor drug doxorubicin (DOX) was encapsulated into the magnetic dextran microgels, and pH/magnetic field dual-responsive release profiles of DOX were demonstrated. Moreover, the release rate of DOX decreased obviously with the increasing MNPs content, probably due to the diffusion barrier for drug movement resulted from the reduced pore size of hydrogel matrix in respond to external magnetic field. These results indicate that the magnetic dextran microgels can serve as stimuli-sensitive drug delivery systems.
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Pharmaceuticals
·
2021
·Vol. 14
·期 2
·101
·
IF 5.863
Lin-Song Li,Bin Ren,Xiaojing Yang,Zhong-Chao Cai,Xue-Jie Zhao,Mei-Xia Zhao
Functionalized gold nanoparticles (AuNPs) have been successfully used in many fields as a result of having low cytotoxicity, good biocompatibility, excellent optical properties, and their ability to target cancer cells. Here, we synthesized AuNP carriers that were modified by hyaluronic acid (HA), polyethylene glycol (PEG), and adipic dihydrazide (ADH). The antitumor drug doxorubicin (Dox) was loaded into AuNP carriers and attached chemically. The Au nanocomposite AuNPs@MPA-PEG-HA-ADH-Dox was able to disperse uniformly in aqueous solution, with a diameter of 15 nm. The results of a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that AuNP carriers displayed very little toxicity toward cells in high doses, although the antitumor properties of Au nanocomposites were significantly enhanced. Cellular uptake experiments demonstrated that AuNPs modified with hyaluronic acid were more readily ingested by HepG2 and HCT-116 cells, as they have a large number of CD44 receptors. A series of experiments measuring apoptosis such as Rh123 and annexin V-FITC staining, and analysis of mitochondrial membrane potential (MMP) analysis, indicated that apoptosis played a role in the inhibition of cell proliferation by AuNPs@MPA-PEG-HA-ADH-Dox. Excessive production of reactive oxygen species (ROS) was the principal mechanism by which the Au nanocomposites inhibited cell proliferation, leading to apoptosis. Thus, the Au nanocomposites, which allowed cell imaging in real-time and induced apoptosis in specific cell types, represent theragnostic agents with potential for future clinical applications in bowel cancer.Keywords:hyaluronic acid;gold nanoparticles;drug carriers;theragnostic agents;imaging
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Biomaterials Science
·
2021
·Vol. 9
·期 7
·2598-2607
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IF 6.843
Linhua Liao,Qiang Chu,Chao Fang,Xiang Li,Gaorong Han
In this study, fine hollow nanocapsules, consisting of NiFe hydroxides (denoted as H–NiFe(OH)x), are designed and synthesized for the delivery of an anticancer drug (Doxorubicin, DOX) and tumour depletion. Owing to its fascinating characteristics of “Fe2+ preservation and regeneration”, H–NiFe(OH)x presents considerable Fenton activity for hydroxyl radical (˙OH) induction. Efficient delivery of DOX is ensured due to its hollow microstructure, and a typical pH-responsive drug release is enabled. More importantly, the intracellular DOX, in addition to its intrinsic antitumour properties, induces extra exogenous H2O2 which favors the production of ˙OH by H–NiFe(OH)x in tumour cells. In consequence, remarkable in vitro and in vivo antitumour properties are successfully achieved. This drug delivery system is particularly inspirational to further studies in the exploration of intelligent therapeutic platforms for combinational tumour therapy.
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DRUG DELIVERY
·
2020
·
IF 4.902
Renna Qiu,Denghua Sun,Yuzhuo Bai,Jiannan Li,Lizhe Wang
Osteosarcoma is the most common primary malignant bone tumor in childhood and adolescence. Currently, surgery combined with chemotherapy is the main treatment for osteosarcoma. However, the long-term survival of patients with metastatic osteosarcoma is unsatisfactory. Therefore, new treatment methods to improve the prognosis of patients with osteosarcoma are required. The present study aimed to develop nanocarriers with both tumor targeting and reduction responsiveness abilities, and to improve the therapeutic effect and reduce toxicity by loading traditional small molecule antitumor drugs. The tumor targeting peptide-decorated, doxorubicin (DOX)-loaded mPEG-P(Phe-co-Cys) nanoparticles were developed successfully through the ring-opening polymerization of amino acids. The peptide VATANST (STP) can specifically bind with vimentin, which is highly expressed on the osteosarcoma cell surface, resulting in tumor targeting effects. The nanoparticle is core–shell structured to protect the loaded DOX during blood flow. The disulfide bonds within the nanoparticles are sensitive to the osteosarcoma microenvironment, which has high glutathione (GSH) levels. Under the enhanced permeability and retention and active tumor targeting effects, the STP-decorated DOX-loaded nanoparticles accumulated in tumor tissues. High GSH levels can rupture disulfide bonds, resulting in the controlled release of DOX, which will cause necrosis of tumor cells. The characteristics of the synthesized nanoparticles, DOX release profiles in vitro and in vivo, cytotoxicity analysis, animal study, and safety evaluation were performed. The nanoparticles could increase the tumor inhibition efficiency against osteosarcoma and reduce the side effects of DOX to major organs. The STP-decorated mPEG-P(Phe-co-Cys) nanoparticles might be a suitable drug delivery system for DOX to treat osteosarcoma.
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OPTICAL MATERIALS
·
2022
·
IF 3.754
Yinyin Chen,Xinying She,Zhouping Yang,Changfang Lu,Wei Zhang,Dongju Feng,Wei Wu,Xianxiang Wang
Doxorubicin hydrochloride (DOX), an anthraquinone-based antibiotic, is widely used in human tumors treatment. However, the residues of DOX in body would pose a threat to the health of heart and liver. Herein, a photochemical sensor NaYF 4 :Yb/Tm@NaYF 4 :Yb-Cit-CD (UCNPs) for detecting DOX has been developed in this paper. The fluorescence emission spectrum of UCNPs under 980 nm laser excitation has a wide range overlap with UV–vis absorption spectrum of DOX. Therefore, the fluorescence emission of UCNPs at 480 nm can be quenched by DOX. The UCNPs sensor has displayed a linear range of 0.05–20 μg/mL with a detection limit (LOD) of 0.005 μg/mL for DOX. Furthermore, the results of recovery for DOX in human serum samples is 98.68–104.20% and in accord with those obtained by HPLC and UV–vis.
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