JOURNAL OF NANOBIOTECHNOLOGY
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2023
·Vol. 21
·期 1
·1-19
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IF 10.2
Xu Yanlong,Du Longhai,Han Binxu,Wang Yu,Fei Jichang,Xia Kuo,Zhai Yonghua,Yu Zuochong
Background Osteosarcoma (OS) is the most prevalent primary malignant bone tumor. However, single-agent chemotherapy exhibits limited efficacy against OS and often encounters tumor resistance. Therefore, we designed and constructed an integrated treatment strategy of photothermal therapy (PTT) combined with chemotherapy and used a surface-encapsulated platelet-osteosarcoma hybrid membrane (OPM) that enhances circulation time and enables OS-specific targeting. Results The OPM functions as a shell structure, encapsulating multiple drug-loaded nanocores (BPQDs-DOX) and controlling the release rate of doxorubicin (DOX). Moreover, near-infrared light irradiation accelerates the release of DOX, thereby extending circulation time and enabling photostimulation-responsive release. The OPM encapsulation system improves the stability of BPQDs, enhances their photothermal conversion efficiency, and augments PTT efficacy. In vitro and ex vivo experiments demonstrate that BPQDs-DOX@OPM effectively delivers drugs to tumor sites with prolonged circulation time and specific targeting, resulting in superior anti-tumor activity compared to single-agent chemotherapy. Furthermore, these experiments confirm the favorable biosafety profile of BPQDs-DOX@OPM. Conclusions Compared to single-agent chemotherapy, the combined therapy using BPQDs-DOX@OPM offers prolonged circulation time, targeted drug delivery, enhanced anti-tumor activity, and high biosafety, thereby introducing a novel approach for the clinical treatment of OS.
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MACROMOLECULAR RESEARCH
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2023
·Vol. 31
·期 3
·181-191
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IF 2.4
Li Jiyu,Zhu Li,Wu Shuai,Wang Guixue,Chen Yidan,Wu Wei
Chemotherapy is the main strategy for inhibiting the tumor growth. However, during the therapy, the side effect of anti-cancer drug will injure normal cells. For reducing the toxic of the free drug, stimuli responsive nanoparticles (NPs) have been prepared base on the pathological acidic environment around tumor for safe and efficient anti-tumor applications. In this study, we fabricated the phenylboronic acid (PBA) modified monomethoxy polyethylene glycol (MEPG) for encapsulating doxorubicin (DOX NPs). In the drug delivery system (DDS), the pH-responsive boric ester could be stable during drug delivery, and enhance DOX rapidly release in tumor lesion under the acidic stimuli. In vitro studies further demonstrated that DOX NPs could efficiently endocytose by tumor cells, and exhibit the similar anti-tumor activity as the free DOX resulting from the pH-responsive drug release profiles under tumor acidic stimuli. In summary, DOX NPs could be a feasible candidate to improve the safe and efficient DOX delivery for improving the potential anti-tumor applications. Graphical abstract
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International Journal of Nanomedicine
·
2023
·
IF 8
Fang Li,Chunli Zheng,Junbo Xin,Fangcheng Chen,Hua Ling,Linlin Sun,Thomas J Webster,Xin Ming,Jianping Liu
A novel method was developed here to prepare albumin-based nanoparticles (NPs) for improving the therapeutic and safety profiles of chemotherapeutic agents. This approach involved crosslinking bovine serum albumin (BSA) using a Schiff base-containing vanillin, into NPs and loading doxorubicin (DOX) into the NPs by incubation. The resultant NPs (DOX-BSA-V-NPs) displayed a particle size of 100.5±1.3 nm with a zeta potential of −23.05±1.45 mV and also showed high drug-loading efficiency and excellent stability with respect to storage and temperature. The encapsulation of DOX into the BSA-V-NPs was confirmed by dynamic scanning calorimetry and Raman spectroscopy. DOX-BSA-V-NPs exhibited a significantly faster DOX release at pH 6.5 than pH 7.4, as well as in a solution with a higher glutathione concentration. In vitro studies showed that the cellular uptake of DOX-BSA-V-NPs was time-dependent, concentration-dependent, and faster than free DOX, while the cytotoxicity of DOX-BSA-V-NPs (IC50 value of 3.693 μg/mL) was superior to free DOX (IC50 value of 4.007 μg/mL). More importantly, DOX-BSA-V-NPs showed a longer mean survival time of 24.83 days, a higher tumor inhibition rate of 56.66%, and a decreased distribution in the heart than other DOX formulations in animal studies using a tumor xenograft model. Thus, the vanillin-based albumin NPs were shown here to be a promising carrier for tumor-targeted delivery of chemotherapeutic agents and, thus, should be further studied.
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International Journal of Nanomedicine
·
2023
·
IF 8
Kai Dong,Zhuang-Zhuang Zhao,Jian Kang,Lei-Ruo Lin,Wen-Ting Chen,Jin-Xi Liu,Xiang-Long Wu,Ting-Li Lu
Background Combined chemotherapy is often affected by the different physicochemical properties of chemotherapeutic drugs, which should be improved by the reasonable design of co-loaded preparations.Purpose A kind of simple but practical graphene oxide (GO) wrapped mesoporous silica nanoparticles (MSN) modified with hyaluronic acid (MSN@GO-HA) were developed for the co-delivery of cinnamaldehyde (CA) and doxorubicin (DOX), in order to enhance their combined treatment on tumor cells and reduce their application defects.Methods The MSNCA@GODOX-HA was constructed by MSNCA (loading CA via physical diffusion) and GODOX-HA (modified with HA and loading DOX via π–π stacking) through the electrostatic adsorption, followed by the physicochemical characterization, serum stability and in vitro release study. Cytotoxicity on different cells was detected, followed by the tumor cell uptake tests. The intracellular reactive oxygen species (ROS) changes, mitochondrial functions and activities of caspase-3/-9 in MCF-7 cells were also evaluated, respectively.Results The MSNCA@GODOX-HA nanoparticles kept stable in FBS solution and achieved pH-responsive release behavior, which was beneficial to increase the accumulation of CA and DOX in tumor cells to enhance the treatment. MSNCA@GODOX-HA exerted higher cytotoxicity to MCF-7 human breast cancer cells than H9c2 cardiac myocyte cells, which were not only attributed to the active targeting to tumor cells by HA, but also related with the activation of intrinsic apoptotic pathway in MCF-7 cells induced by CA, which was mediated by the specific ROS signal amplification and the interference with mitochondrial function. Moreover, the efficacy of DOX was also enhanced by the above process.Conclusion The establishment of the MSNCA@GODOX-HA nanoparticles played a role in promoting strengths and restricting shortcomings of CA and DOX, thereby exerting their function and achieving efficient treatment against cancer.
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International Journal of Nanomedicine
·
2023
·
IF 8
Hongxiang Wei,Jinyuan Chen,Shenglin Wang,Feihuan Fu,Xia Zhu,Chaoyang Wu,Zhoujie Liu,Guangxian Zhong,Jianhua Lin
Purpose The primary goal of the present study was to develop the nano-drug consisting of doxorubicin and exosome derived from mesenchymal stem cells, and to explore its effect on osteosarcoma in vitro.Methods The exosomes were isolated from bone marrow MSCs (BM-MSCs) by an Exosome Isolation Kit. The exosome-loaded doxorubicin (Exo-Dox) was prepared by mixing exosome with Dox-HCl, desalinizing with triethylamine and then dialyzing against PBS overnight. The nanoparticle tracking analysis (NTA) and transmission electron microscope (TEM) were used to characterize of the exosome and Exo-Dox. The cytotoxicity of Exo-Dox was determined by CCK-8 assay. Further, the cellular uptake of different drugs was analyzed using inverted fluorescence microscope and flow cytometry.Results The typical exosome structures can be observed by TEM. After loading with doxorubicin, its size is larger than free exosome. Compared with the free Dox, the prepared Exo-Dox showed enhanced cellular uptake efficiency and anti-tumor effect in osteosarcoma MG63 cell line but low cytotoxicity in myocardial H9C2 cell line.Conclusion The prepared Exo-Dox could be used as an excellent chemotherapeutic drug for treatment of osteosarcoma in vitro. Considering the tumor-homing feature of BM-MSCs, the Exo-Dox may be a good candidate for targeted osteosarcoma treatment in future study.
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JOURNAL OF ETHNOPHARMACOLOGY
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2022
·
IF 5.195
Zhen Xue,Lingxin Zhuo,Bowen Zhang,Lingmeng Zhu,Xinran Xiang,Chunxia Zhang,Wenyuan Liu,Guangguo Tan,Wenting Liao
Ethnopharmacological relevance Qifu decoction (QFD) is a famous traditional Chinese medicine (TCM) composed of Astragali Radix (HuangQi) and Aconiti Lateralis Radix Praeparaia (Fuzi), which can alleviate doxorubicin (DOX)-induced cardiotoxicity (DIC). However, its protective mechanism remains obscured. Aim of the study The present study aimed to uncover the cardioprotective mechanism and the synergistic effect of QFD against DIC in mice. Materials and methods The cardioprotective activity of QFD against DIC was assessed by electrocardiogram, serum biochemical assays and histopathology. Mass spectrometry-based metabolomic approach was conducted to elucidate the preventive mechanisms of QFD, HuangQi decoction (HQD), and Fuzi decoction (FZD) against DIC. QFD, HQD, FZD-targeted metabolic pathways were identified and compared to investigate the synergistic mechanism of QFD by computational systems analysis. Quantitative real-time PCR (qRT-PCR) was further employed to validate the key metabolic pathways at the level of the gene. Results The electrocardiogram combined with the biochemical analysis and histopathology showed that the protection effects were sorted as QFD > HQD ≈ FZD. A total of 41 metabolites contributing to DIC were identified in the mice serum, among which 32, 12 and 10 metabolites were significantly reverted by QFD, HQD and FZD, respectively. Metabolic pathway analysis revealed that DOX perturbed 12 metabolic pathways, and QFD, HQD, and FZD-treated groups could significantly reverse 12, 7 and 6 metabolic pathways of these 12 metabolic pathways. Metabolic pathway and qRT-PCR revealed that QFD could protect DIC mainly by regulating energy metabolism, amino acids metabolism, arachidonic acid metabolism and glycerophospholipid metabolism, and HQD and FZD mutually reinforced each other. Conclusion These evidences revealed that QFD was a promising drug candidate for DIC by maintaining metabolic homeostasis. Meanwhile, this work provided a useful approach for evaluating the efficacy and the synergistic effects of TCMs against cardiomyopathy .
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Biomaterials Science
·
2019
·Vol. 7
·期 9
·3662-3674
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IF 5.251
Yiming Liu,Ke Li,Youshen Wu,Jingwen Ma,Peng Tang,Yongchun Liu,Daocheng Wu
To improve the tumor synergistic therapeutic effects of carrier-free dual-drug delivery systems and realize ultralow dose administration, we developed a tumor targeting and high-efficiency synergistic chemotherapy system (HA-Gn@DPGn NPs) based on polyvinyl alcohol (PVA) reinforced gossypolone (Gn) and doxorubicin (DOX) π–π stacking nanoparticles (DPGn NPs), in which PVA filled the gaps between Gn and DOX and bridged Gn and DOX tightly. Hyaluronic acid modifier hyaluronic acid-gossypolone (HA-Gn) was covered on the surface of DPGn NPs to form HA-Gn@DPGn NPs that procured active targeting properties. This system presented a spherical shape with a uniform hydrodynamic size of 87 ± 6.8 nm, a high drug loading of 80.31%, and high stability. FTIR and UV spectra demonstrated that HA-Gn was covered on the surface of the system and showed significant π–π stacking properties. A considerably low combination index of Gn and DOX (0.1862) was determined at an ultra-low dose of DOX under a Gn : DOX ratio of 50 : 1. HA-Gn@DPGn NPs also demonstrated excellent tumor synergistic therapeutic efficacy (TIR > 87%) at an ultralow dose of DOX and Gn. This system demonstrates high tumor comprehensive synergistic therapeutic efficacy at an ultralow drug dose with multiple favorable therapeutic characteristics, including negligible side effects, tumor targeting ability and thermal-responsive drug release, and thus has considerable potential for tumor synergistic therapy.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2018
·Vol. 19
·期 11
·3658
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IF 3.687
Zhi-Meng Xu,Cheng-Bin Li,Qing-Ling Liu,Ping Li,Hua Yang
Ginsenoside Rg1, a saponin that is a primary component of ginseng, has been demonstrated to protect hearts from diverse cardiovascular diseases with regulating multiple cellular signal pathways. In the present study, we investigated the protective role of ginsenoside Rg1 on doxorubicin-induced cardiotoxicity and its effects on endoplasmic reticulum stress and autophagy. After pre-treatment with ginsenoside Rg1 (50 mg/kg i.g.) for 7 days, male C57BL/6J mice were intraperitoneally injected with a single dose of doxorubicin (6 mg/kg) every 3 days for four injections. Echocardiographic and pathological findings showed that ginsenoside Rg1 could significantly reduce the cardiotoxicity induced by doxorubicin. Ginsenoside Rg1 significantly inhibited doxorubicin-induced formation of autophagosome. At the same time, ginsenoside Rg1 decreased the doxorubicin-induced cardiac microtubule-associated protein-light chain 3 and autophagy related 5 expression. Ginsenoside Rg1 can reduce endoplasmic reticulum dilation caused by doxorubicin. Compared with the doxorubicin group, the expression of cleaved activating transcription factor 6 and inositol-requiring enzyme 1 decreased in group ginsenoside Rg1. Treatment with ginsenoside Rg1 reduces the expression of TIF1 and increases the expression of glucose-regulated protein 78. In the ginsenoside Rg1 group, the expression of p-P70S6K, c-Jun N-terminal kinases 1 and Beclin1 declined. These results indicate that ginsenoside Rg1 may improve doxorubicin-induced cardiac dysfunction by inhibiting endoplasmic reticulum stress and autophagy.Keywords:ginsenoside Rg1;doxorubicin;cardiotoxicity;autophagy;endoplasmic reticulum stress
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MOLECULAR PHARMACEUTICS
·
2019
·
IF 4.396
Ying Li,Jing Luo,Meng-Ting Lin,Pei Zhi,Wang-Wei Guo,Min Han,Jian You,Jian-Qing Gao
Doxorubicin (DOX) is a first-line chemo drug for cancer therapy, yet it fails to treat multi-drug-resistant tumors. Hypoxia is a major causative factor leading to chemotherapy failure. Particularly, hypoxia up-regulates its responsive transcription factor—hypoxia-inducible factors (HIF)—to induce the overexpression of drug resistant genes. Metformin (MET) is recently found to cooperate with DOX against multiple tumors. As a mitochondrial inhibitor, MET could suppress tumor oxygen consumption, and thereby modulate the hypoxic tumor microenvironment. In this study, we used cationic liposomes to codeliver both DOX and MET for treating multi-drug-resistant breast cancer cells—MCF7/ADR. Faster release of MET enhanced the cytotoxicity of DOX through attenuating hypoxic stress both in vivo and in vitro. MET diminished the cellular oxygen consumption and inhibited HIF1α and P-glycoprotein (Pgp) expression in vitro. In addition, the dual-drug-loaded liposomes increased tumor targeting and intratumoral blood oxygen saturation, which suggested that the tumor reoxygenation effect of MET facilitated the exertion of its synergistic activity with DOX against MCF7/ADR xenografts. In general, our study represents a feasible strategy to boost the therapeutic effect in treating multi-drug-resistant cancer by improving the hypoxic tumor microenvironment.
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2019
·Vol. 23
·期 3
·2174-2183
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IF 4.658
Haiman Mu,Haiwen Liu,Jiayi Zhang,Jianhua Huang,Chen Zhu,Yue Lu,Yueping Shi,Yi Wang
In addition to the known antitumour effects of ursolic acid (UA), increasing evidence indicates that this molecule plays a role in cardiac protection. In this study, the effects of ursolic acid on the heart in mice treated with doxorubicin (DOX) were assessed. The results showed that ursolic acid improved left ventrical fractional shortening (LVFS) and left ventrical ejection fraction (LVEF) of the heart, increased nitrogen oxide (NO) levels, inhibited reactive oxygen species (ROS) production and decreased cardiac apoptosis in mice treated with doxorubicin. Mechanistically, ursolic acid increased AKT and endothelial nitric-oxide synthase (eNOS) phosphorylation levels, and enhanced eNOS expression, while inhibiting doxorubicin induced eNOS uncoupling through NADPH oxidase 4 (NOX4) down-regulation. These effects of ursolic acid resulted in heart protection from doxorubicin-induced injury. Therefore, ursolic acid may be considered a potential therapeutic agent for doxorubicin-associated cardiac toxicity in clinical practice.
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Nanomedicine
·
2019
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IF 4.717
Qian Li,Mengmeng Hou,Junjie Ren,Shiyu Lu,Zhigang Xu,Chang Ming Li,Yuejun Kang,Peng Xue
Aim: Hollow mesoporous copper sulfide nanocapsules conjugated with poly(ethylene glycol) (PEG), doxorubicin and chlorin e6 (HPDC) were synthesized for fluorescence imaging and multimodal tumor therapy. Materials & methods: HPDC were synthesized by encapsulating chlorin e6 and doxorubicin into PEGylated nanocapsules via a simple precipitation method. The photothermal/photodynamic effects, drug release, cellular uptake, imaging capacities and antitumor effects of the HPDCs were evaluated. Results: This smart nanoplatform is stimulus-responsive toward an acidic microenvironment and near infrared laser irradiation. Moreover, fluorescence imaging-guided and combined photothermal/photodynamic/chemotherapies of tumors were promoted under laser activation and led to efficient tumor ablation, as evidenced by exploring animal models in vivo. Conclusion: HPDCs are expected to serve as potent and reliable nanoagents for achieving superior therapeutic outcomes in cancer management.
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Artificial Cells Nanomedicine and Biotechnology
·
2018
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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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