BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Zhenzhen Chen,Qinbiao Huang,Yutong Song,Xianquan Feng,Lingjun Zeng,Zhihong Liu,Xiaomu Hu,Chun Tao,Lie Wang,Yafeng Qi,Hongtao Song
Melanoma is a highly aggressive form of skin cancer with limited therapeutic options. Chemo-photothermal combination therapy has demonstrated potential for effectively treating melanoma, and transdermal administration is considered the optimal route for treating skin diseases due to its ability to bypass first-pass metabolism and enhance drug concentration. However, the stratum corneum presents a formidable challenge as a significant barrier to drug penetration in transdermal drug delivery. Lipid-nanocarriers, particularly cubosomes, have been demonstrated to possess significant potential in augmenting drug permeation across the stratum corneum. Herein, cubosomes co-loaded with doxorubicin (DOX, a chemotherapeutic drug) and indocyanine green (ICG, a photothermal agent) (DOX-ICG-cubo) transdermal drug delivery system was developed to enhance the therapeutic efficiency of melanoma by improving drug permeation. The DOX-ICG-cubo showed high encapsulation efficiency of both DOX and ICG, and exhibited good stability under physiological conditions. In addition, the unique cubic structure of the DOX-ICG-cubo was confirmed through transmission electron microscopy (TEM) images, polarizing microscopy, and small angle X-ray scattering (SAXS). The DOX-ICG-cubo presented high photothermal conversion efficiency, as well as pH and thermo-responsive DOX release. Notably, the DOX-ICG-cubo exhibited enhanced drug permeation efficiency, good biocompatibility, and improved in vivo anti-melanoma efficacy through the synergistic effects of chemo-photothermal therapy. In conclusion, DOX-ICG-cubo presented a promising strategy for melanoma treatment.
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JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
·
2016
·Vol. 16
·期 6
·5740-5745
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IF 1.338
Deng Jiangming,Mo Yunfei,Liu Jianghui,Guo Rui,Zhang Yi,Xue Wei,Zhang Yuanming
Inorganic nanoparticles have been widely used in biomedical field. In this paper, we try to study the use of three types of inorganic nanoparticles (i.e., SnS2, BiOCl and SnS2-incorporated BiOCl (SnS2/BiOCl)) as doxorubicin (DOX) carriers. Firstly, SnS2,
BiOCl and SnS2/BiOCl were synthesised, then were characterized by TEM, nanoparticles size and zeta potential. Next the drug release and cell viability test were carried out. The cell viability test indicated that the drug carriers can effectively kill HeLa cells while maintaining
low cytotoxicity against normal cells-fibroblasts. The results show the potential of SnS2/BiOCl nanoparticles for antitumor applications.
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Nanoscale
·
2022
·Vol. 14
·期 8
·3097-3111
·
IF 8.307
Lu Wang,Genhua Liu,Yunping Hu,Shuangquan Gou,Tingting He,Qian Feng,Kaiyong Cai
The lymphatic system provides a main route for the dissemination of most malignancies, which was related to high mortality in cancer patients. Traditional intravenous chemotherapy is of limited effectiveness on lymphatic metastasis due to the difficulty in accessing the lymphatic system. Herein, a novel lymphatic-targeting nanoplatform is prepared by loading doxorubicin (DOX) into sub-50 nm polypyrrole nanovesicles (PPy NVs). The PPy NVs possessed hollow spherical morphologies and a negative surface charge, leading to high drug loading capacity. These vesicles can also convert near-infrared (NIR) light into heat and thus can be used for tumor thermal ablation. DOX loaded PPy NVs (PPy@DOX NVs) along with NIR illumination are highly effective against 4T1 breast cancer cells in vitro. More importantly, following subcutaneous (SC) injection, a direct lymphatic migration of PPy@DOX NVs is confirmed through fluorescence observation of the isolated draining nodes. The acidic conditions in metastatic nodes might subsequently trigger the release of the encapsulated DOX NVs based on their pH-sensitive release profile. In a mouse model bearing 4T1 breast cancer, lymphatic metastases, as well as lung metastases, are significantly inhibited by nanocarrier-mediated trans-lymphatic drug delivery in combination with photothermal ablation. In conclusion, this platform holds great potential in impeding tumor growth and metastasis.
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ACS Applied Bio Materials
·
2021
·
IF 0
Minjiang Chen,Xiaoling Xu,Gaofeng Shu,Chenying Lu,Jiahui Wu,Xiuling Lv,Jingjing Song,Fazong Wu,Chunmiao Chen,Nannan Zhang,Yuyin Du,Jun Wang,Min Xu,Shiji Fang,Qiaoyou Weng,Yiling Zhu,Yuan Huang,Zhongwei Zhao,Yongzhong Du,Jiansong Ji
Lactic acid in the tumor microenvironment is highly correlated with the prognosis of tumor chemoembolization, but there are limited clinical strategies to deal with it. To improve the efficacy, NaHCO3 nanoparticles are innovatively introduced into drug-loaded microspheres to neutralize lactic acid in the tumor microenvironment. Here we showed that multifunctional ethyl cellulose microspheres dual-loaded with doxorubicin (DOX) and NaHCO3 nanoparticles (DOX/NaHCO3-MS) presented excellent antitumor effects by improving the pH of the tumor microenvironment. The homeostasis of the tumor microenvironment was continuously disturbed due to the sustained release of NaHCO3 nanoparticles, which also led to a significant increase in tumor cell apoptosis (compared with the control and DOX-MS groups). We also showed that the administration of DOX/NaHCO3-MS via the hepatic artery in a rabbit model of VX2 orthotopic liver cancer resulted in optimal antitumor efficacy, and the area of tumor necrosis at the embolization site was significantly increased and the proliferation of tumor cells was significantly weakened. The designed DOX/NaHCO3-MS exhibited strong synergistic antitumor effects of embolization, chemotherapy, and tumor microenvironment improvement. The present microspheres provided a strategy for the enhancement of the chemoembolization of hepatocellular carcinoma, which could also be extended to other clinical embolization treatments for blood-rich solid tumors.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2013
·
IF 3.554
Jiahui Yu,Xiangyang Li,Yu Luo,Wei Lu,Jin Huang,Shiyuan Liu
This research is aimed to develop a kind of poly(ethylene glycol) shell-sheddable magnetic nanomicelle as the carrier of doxorubicin (Dox) in order to enhance its cellular uptake ability, and achieve synchronous magnetic resonance imaging (MRI)-visible function. Firstly, the five-member rings in poly ( l -succinimide) (PSI) were successively opened by the amino terminated disulfide-linked poly(ethylene glycol) monomethyl ether (mPEG-SS-NH 2 ) and dopamine (DA) to produce the graft copolymer of mPEG-SS-NH- graft -PAsp-DA. And then, drug-loaded magnetic nanomicelles of mPEG-SS-NH- graft -PAsp-DA@Fe 3 O 4 .Dox were obtained by the Fe 3 O 4 nanoparticle-induced self-assembly of mPEG-SS-NH- graft -PAsp-DA. These magnetic nanomicelles showed spherical shapes with average particle size of about 120 nm measured by dynamic light scattering (DLS). Due to the detachment of PEG shell in the presence of dithiothreitol (DTT), the magnetic nanomicelles showed accelerated in vitro release of Dox, and enhanced cellular uptake ability. Compared with free Dox, the Dox-loaded magnetic nanomicelles showed essential decreased cytotoxicity against Bel-7402 cell line. If its high r 2 relaxation rate (221 mM −1 s −1 ) and good negative contrast effect for magnetic resonance imaging (MRI) were taken into account, mPEG-SS-NH- graft -PAsp-DA@Fe 3 O 4 .Dox could be used as MRI-detectable drug carrier of Dox with enhanced cellular uptake ability.
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CHINESE JOURNAL OF POLYMER SCIENCE
·
2019
·Vol. 37
·期 12
·1224-1233
·
IF 2.804
Gong Heng-Ye,Chen Yan-Gui,Yu Xing-Su,Xiao Hong,Xiao Jin-Peng,Wang Yong,Shuai Xin-Tao
Drug-resistance and drastic side effects are two major issues of traditional chemotherapy which may result in trail failure even death. Nanoparticle-mediated multidrug combination treatment has been proven to be a feasible strategy to overcome these challenges. In the present study, amphipathic block polymer of methoxyl poly(ethylene glycol)-poly(aspartyl(dibutylethylenediamine)- co -phenylalanine) (mPEG-P(Asp(DBA)- co -Phe)) was synthesized and self-assembled into pH-responsive polymeric vesicle. The vesicle was utilized to co-deliver cancer-associated epidermal growth factor (EGFR) inhibitor of afatinib and DNA-damaging chemotherapeutic doxorubicin hydrochloride (DOX) for enhanced non-small-cell lung cancer (NSCLC) therapy. As evaluated in vitro , the pH-responsive design of nanovesicle resulted in a rapid release of encapsulated drugs into tumor cells and caused enhanced cell apoptosis. In addition, in vivo therapeutic studies were conducted and the results evidenced that the co-delevery of DOX and afatinib using pH-sensitive nanovector was a promising strategy for NSCLC treatment.
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Acta Biomaterialia
·
2021
·
IF 8.947
Dongsheng Yu,Yazhou Wang,Jifeng Chen,Shuang Liu,Shaohui Deng,Chengbo Liu,Iain McCulloch,Wan Yue,Du Cheng
Semiconducting polymer (SP) is a promising photothermal agent in the antitumor application, but the co-delivery of the second near-infrared window (NIR-II)-based SPs with chemotherapeutic drug (e.g., doxorubicin (DOX)) remains a challenge. Here, SPs were firstly improved via backbone and alkyl side-chain engineering, and afterward, SPs and pH-sensitive prodrug copolymer self-assembled into a nanoparticle for a photoacoustic (PA)-imaging guided combination of photothermal therapy and chemotherapy. SP-encapsulated nanoparticles exhibited a high photothermal conversion efficiency of 45% at a relatively low power level of NIR irradiation (0.3 W/cm 2 for 5 min). DOX was rapidly released in response to the acidic lysosomal environment. PA and fluorescence imaging confirmed that the photothermal therapy effectively drove DOX penetration inside tumor tissue, and it resulted in the killing of the surviving tumor cells from hyperthermia. The synergistic effect of SP-based photothermal therapy and DOX-induced chemotherapy was verified in vivo . Overall, the co-delivery of the SP and DOX using pH-sensitive nanoparticles represents a feasible strategy for photothermal therapy with potentially synergistic drug effects. Statement of significance Recent years have yielded great progress in semiconducting polymers (SPs)-based photothermal therapy for anticancer treatment. However, studies about molecular weight and side-chain of SPs on photothermal conversion efficiency are limited, and investigation of controlled codelivery with chemotherapeutic drug is lacking. Here, we improved the SPs performance via backbone and side-chain engineering, and afterward offered a pH-sensitive DOX-conjugated amphiphilic copolymer to encapsulate SPs. SP-encapsulated nanoparticles exhibited high photothermal conversion efficiency at a clinically feasible power level of NIR irradiation. NIR irradiation-generated hyperthermia not only killed tumor cells but also promoted DOX penetration inside the tumor tissue to ablate the tumor cells that survived hyperthermia. The synergistic effect of SP-based photothermal therapy and DOX-induced chemotherapy was verified in vivo .
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Journal of Biomedical Nanotechnology
·
2015
·Vol. 11
·期 10
·1764-1775
·
IF 5.338
Yin Qi,Shen Jianan,Yu Haijun,Huang Yongzhuo,Zhang Zhiwen,Li Yaping
The clinical success of anthracyclines-containing chemotherapy for breast cancer is mainly restricted by cardiac damage and the development of multidrug resistance (MDR). For efficient reversal of drug resistance, doxorubicin (DOX) loaded multifunctional bioreducible micelles were constructed
from a new amphiphilic copolymer consisting of polyethylene glycol and poly[bis(2-hydroxylethyl)-disulfide-diacrylate-β-histamine] and characterized. The introduction of imidazole group endowed the micelles with endosomal buffering capacity and improved the endosomal escape. The
reductionresponsiveness of the micelles promoted DOX release. The activity of P-glycoprotein, one of the most well-described drug-efflux pumps, and glutathione S-transferase, an important detoxification enzyme, were also inhibited by the micelles. The accumulation of DOX in tumor after intravenous
administration of the drug-loading micelles was increased in drug resistant tumor-bearing mice. These results indicated that the micelle was a promising drug delivery system for MDR cancer therapy.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Xinyi Li,Hui Song,Yiwen Yuan,Na Jiang,Wei Duan,Tianzhao Xu,Chang Liu,Xinghui Liu
Cardiovascular diseases have long posed a significant threat to public health. Among them, myocarditis is a major category of cardiovascular disorders that is characterized by high mortality during its acute phase, necessitating urgent medical attention. This study aims to explore the therapeutic effects and underlying mechanisms of Spi1-mediated gene regulation in chemotherapy induced cardiomyopathy. To validate our findings, we employed bioinformatics analysis methods and established myocarditis models using the chemotherapeutic drug doxorubicin in both cellular and animal models. Our results demonstrated that the inhibition of Spi1 significantly suppressed inflammatory factor expression in H9C2 rat cardiomyocytes. Furthermore, in C57BL/6 mouse model, Spi1 inhibition was shown to improve cardiac function and alleviate both myocardial inflammation and fibrosis in mice with doxorubicin-induced myocarditis. Mechanistic investigations revealed that Spi1 suppression altered the expression of genes associated with immune response, cell differentiation and proliferation. Notably, Spi1 modulates the expression of YTHDF2, thereby influencing the PI3K/AKT/mTOR signaling pathway and subsequently regulating the inflammatory response. Collectively, these findings suggest that Spi1 plays a pivotal role in doxorubicin-induced myocarditis by mitigating inflammatory responses and myocardial injury through the regulation of YTHDF2 and the PI3K/AKT/mTOR signaling pathways, offering a promising therapeutic target for the treatment of myocarditis.
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DRUG DELIVERY
·
2025
·
IF 8.1
Yang Wang,Yanan Fu,Meiying Wu,Haoqiang Wan,Xinchun Chen,Lanlan Ge,Chenyan Shi,Yangfan Li,Xiaobin Zeng,Tianqi Wang
The chemotherapeutic drug doxorubicin (DOX) has been demonstrated to trigger pyroptosis in tumor cells at exceptionally high concentrations. Nevertheless, the administration of DOX at suprapharmacological doses could cause acute off-target cytotoxicity and severe adverse effects. Herein, a biflavonoid derivative, F24, was found to improve the sensitivity of hepatocellular carcinoma (HCC) cells to low-dose DOX and reduce the adverse effects of DOX. We demonstrated that F24 synergized with low-dose DOX to increase pyroptosis and autophagy in HCC cells through dual-target CDK6 inhibition/p53 activation at a proper ratio. To achieve this synergistic effect, nanodiscs with large hydrophobic cavities were selected to codeliver the low-dose hydrophobic drugs DOX and F24 (DOX-F24@Nanodisc, DF@N), which improved the tumor accumulation of the two drugs and ensured precise drug ratio integrity within the tumor cells. DF@N can trigger gasdermin-E (GSDME)-based pyroptosis in tumor cells, accompanied by the cleavage of caspase-3. Strikingly, knocking out GSDME or caspase-3 redirected DF@N-driven cellular death from the pyroptosis pathway to the apoptotic pathway. Furthermore, DF@N administration suppressed tumor growth and activated pyroptosis in a Huh7 mouse xenograft tumor model. Overall, F24 was found to induce autophagy by targeting CDK6 and had a synergistic effect on DOX-induced pyroptosis. These results indicate that the pyroptosis-induced DF@N nanodisc system provides an effective and secure therapeutic strategy for treating HCC.
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LANGMUIR
·
2025
·
IF 3.9
Haiqian Zhao,Fang Chen,Minghong Feng,Wenjing Lin,Hangbo Yue,Jianwei Guo,Chufen Yang
To improve the stability and drug-controlled release capability of folic acid-modified pH-responsive polymeric mixed micelles FA-PEG-PHEMA-PDEAEMA (FA-P1)/PCL-PHEMA-PPEGMA (P2), the hydroxyl termini of the PHEMA blocks in polymers FA-P1 and P2 were esterified with selenooctanoic acid (SA) to produce FA-P1-SA and P2-SA, which were capable of self-cross-linking and exhibited reduction responsiveness. Thus, folic acid-modified dual-responsive diselenide-containing mixed cross-linked micelles composed of FA-P1-SA and P2-SA were constructed and employed for the delivery of doxorubicin (DOX). Structural characterization by 1H NMR, FT-IR, Raman spectroscopy, and GPC confirmed successful SA conjugation at an esterification degree of approximately 70%. Experimental and dissipative particle dynamics (DPD) analyses showed that the DOX loading content and encapsulation efficiency of the FA-containing mixed cross-linked micelles (MCLM@DOX) (1:1 mass ratio of FA-P1-SA/P2-SA) were slightly lower than those of non-cross-linked micelles (MMSA@DOX), yet afforded superior retention under physiological conditions (16.11% vs 22.49% release at 120 h) and rapid, stimuli-triggered release (75.20% vs 83.32%) in reductive, acidic conditions. Cytotoxicity assays indicated minimal polymer toxicity after SA modification. Furthermore, FA-containing MCLM@DOX exhibited relatively good tumor-targeting and anticancer efficacy compared with FA-free counterparts (MCLM1@DOX).
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JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE
·
2013
·Vol. 25
·期 3
·723-731
·
IF 2.141
Shi Zhonggen,Guo Rui,Li Weichang,Zhang Yi,Xue Wei,Tang Yu,Zhang Yuanming
Chitosan (CS) was first modified hydrophobically with deoxycholic acid (DCA) and then with polyethylene glycol (PEG) to obtain a novel amphiphilic polymer (CS–DCA–PEG). This was covalently bound to folic acid (FA) to develop nanoparticles (CS–DCA–PEG–FA) with tumor cell targeting property. The structure of the conjugates was characterised using Fourier transform infrared and 1 H nuclear magnetic resonance spectroscopy and X-ray diffraction. Based on self-aggregation, the conjugates formed nanoparticles with a low critical aggregation concentration of 0.035 mg/ml. The anti-cancer drug doxorubicin (DOX) was encapsulated into the nanoparticles with a drug-loading capacity of 30.2 wt%. The mean diameter of the DOX-loaded nanoparticles was about 200 nm, with a narrow size distribution. Transmission electron microscopy images showed that the DOX-loaded nanoparticles were spherical. The drug release was studied under different conditions. Furthermore, the cytotoxic activities of DOX in CS–DCA–PEG–FA nanoparticles against folate receptor (FR)-positive HeLa cells and FR-negative fibroblast 3T3 cells were evaluated. These results suggested that the CS–DCA–PEG–FA nanoparticles may be a promising vehicle for the targeting anticancer drug to tumor cells.
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