Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 27
·5464-5472
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IF 4.543
Zhipeng Zhang,Yun Wang,Shaohui Xu,Yanna Yu,Abid Hussain,Yuanyuan Shen,Shengrong Guo
The design of an ideal drug delivery system with targeted recognition and minimized premature release, especially controlled and specific release that is triggered by endogenous and exogenous dual-stimuli, is a great challenge. A biotin receptor-targeted, near-infrared (NIR) irradiation and redox responsive nano-system has now been developed. The nano-system was constructed by filling the interior of Au nanocages with doxorubicin as a chemotherapy agent trapped in tetradecanol, followed by surface conjugation of biotinylated poly(ethylene glycol)–poly(curcumin-dithiodipropionic acid) (Biotin–PEG–PCDA) as a macromolecular chemosensitizer. Once the nano-system had been delivered into MCF-7/ADR cells by biotin receptor mediated recognition and endocytosis, drug release was triggered by degradation of PCDA via a glutathione induced redox reaction in combination with a solid–liquid change of tetradecanol by photothermal effects under NIR irradiation, which could minimize premature drug release and then maximize the therapeutic efficacy.
研究领域:
癌症治疗
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药物递送
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纳米技术
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材料科学
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生物医学工程
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DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2020
·
IF 5.88
Xuan Liu,Chen Wang,Xueyan Wang,Chen Tian,Yuhua Shen,Manzhou Zhu
Designing a proper intelligent platform to target cancer cells accurately and reducing its toxic side effects on normal tissues remain a challenge in medicine application. Herein, a novel dual-targeted and tumor microenvironment-triggered Fe 3 O 4 @carbon(C)/ZnO-doxorubicin (DOX) -folic acid (FA) drug delivery system with porous structure was designed and fabricated for the first time. The co-presence of Fe 3 O 4 core and FA molecules functioned successfully could successfully realize the magnetic targeting and cancer cell-specific targeting. In addition, pH-responsive ZnO and porous carbon both derived directly from zinc-2-methylimidazolate complex (Zn-ZIF) could play the roles of “gatekeeper” and photothermal agent, respectively. The former could efficiently block the drug within mesoporous in blood environment for decreasing the damage to the normal tissues and achieving the controlled DOX release in the simulated and real acidic tumor microenvironment. And the latter could exhibit the intrinsic photothermal conversion efficiency upon 638 nm laser irradiation. Therefore, the Fe 3 O 4 @C/ZnO-DOX-FA nanoplatform integrated dual targeting, controlled chemotherapy with photothermal therapy (PTT) for cancer, displaying a significantly superior synergistic anticancer efficiency both in vitro and in vivo experiments to either monotherapy. Above results suggested the prepared nanoplatforms might be a promising candidate for effectively synergetic therapeutics to cancers.
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高影响因子
Cancer Nanotechnology
·
2024
·Vol. 15
·期 1
·1-15
·
IF 4.5
Lin Xiuyun,Liu Jie,Wu Guangfeng,Yang Xiu,Yan Wenqiang,Fan Nanfeng,Li Hui
Background Cancer cells can resist chemotherapy through various mechanisms, diminishing treatment outcomes. Research had indicated that combining miR-122 with doxorubicin (DOX) can improve hepatocellular carcinoma (HCC) therapy.Results To explore this, we created a one-pot co-delivery system, Fe-miR-122/DOX, by coordinating miR-122, DOX, and FeII ions into nanoparticles. These nanoparticles display uniform particle sizes, well-defined morphology, and exceptional colloidal stability in 10% FBS and 20% FBS solution over 24 h. When the ratio of DOX to miR-122 was set at 20:1, the loading efficiency of both drugs reached 54.7% and 55.5%, respectively. Cell experiments confirmed that Fe-miR-122/DOX efficiently delivers both miR-122 and DOX, enabling cytoplasmic delivery through lysosomal escape, facilitated by the positive charge of the nanoparticles. Functionally, miR-122 increases intracellular accumulation of DOX by downregulating P-glycoprotein (P-gp) expression, and it promotes apoptosis by downregulating B-cell lymphoma 2 (Bcl-2), which leads to the upregulation of Caspase-3. Additionally, Fe-miR-122/DOX disrupts cIAPs-mediated anti-apoptotic signals, downregulates PARP-1 expression, hinders DNA repair, promotes DNA fragmentation, enhances caspase-3 expression, and triggers programmed cell death, synergistically enhancing its antitumor efficacy. This synergistic mechanism disrupts DNA repair, amplifying DNA damage and apoptosis. Our cytotoxicity and apoptosis assays (with a HepG2 cell apoptosis rate of 85.98%) demonstrated the potent antitumor capability of Fe-miR-122/DOX.Conclusion sThis innovative system has demonstrated good biocompatibility and has the potential to transform HCC therapy. Future research could focus on optimizing the co-delivery system and assessing its efficacy in clinical trials.
研究领域:
肿瘤学
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药理学
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分子生物学
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纳米技术
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高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2017
·
IF 4.233
Xian Li,Yue Yan,Yuanzhe Lin,Jian Jiao,Da Wang,Donghua Di,Ying Zhang,Tongying Jiang,Qinfu Zhao,Siling Wang
In this study, hollow mesoporous carbon nanoparticles (HMCN) and mesoporous carbon nanoparticles (MCN) were used as near-infrared region (NIR) nanomaterials and drug nanocarriers were prepared using different methods. A comparison between HMCN and MCN was performed with regard to the NIR-induced photothermal effect and drug loading efficiency. The results of NIR-induced photothermal effect test demonstrated that HMCN-COOH had a better photothermal conversion efficacy than MCN-COOH. Given the prominent photothermal effect of HMCN-COOH in vitro , the chemotherapeutic drug DOX was chosen as a model drug to further evaluate the drug loading efficiencies and NIR-triggered drug release behaviors of the nanocarriers. The drug loading efficiency of DOX/HMCN-COOH was found to be up to 76.9%, which was higher than that of DOX/MCN-COOH. In addition, the use of an 808 nm NIR laser markedly increased the release of DOX from both carbon carriers in pH 5.0 PBS and pH 7.4 PBS. Cellular photothermal tests involving A549 cells demonstrated that HMCN-COOH had a much higher photothermal efficacy than MCN-COOH. Cell viability experiments and flow cytometry were performed to evaluate the therapeutic effect of DOX/HMCN-COOH and the results obtained demonstrated that DOX/HMCN-COOH had a synergistic therapeutic effect in cancer treatment involving a combination of chemotherapy and photothermal therapy.
研究领域:
材料科学
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纳米技术
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癌症治疗
·
药物递送系统
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DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2026
·
IF 5.8
Fatemeh Sasanipoor,Zhiqing Zhang,Ruyan Zhang,Gan Ning,Ting Zhou,Xiufeng Wang,Fang Wang
Achieving precise integration of molecular targeting, controlled drug release, and efficient photothermal conversion remains a critical challenge in the development of synergistic cancer nanotherapies. Here, we presented a programmable dual-aptamer DNA–MoS2 quantum dot (QDs) nanoplatform, constructed via multivariate hydrothermal synthesis and rolling circle amplification (RCA). Systematic optimization identified glutathione as the optimal sulfur source, resulting in the preparation of ultrasmall MoS2-QDs with strong 808 nm absorption, high colloidal stability, and excitation-dependent fluorescence. Covalent conjugation of these QDs to an RCA-derived DNA scaffold enabled high-density assembly of MUC1 and AS1411 aptamers and facilitated efficient doxorubicin (DOX) intercalation within GC-rich duplex regions. The resulting nanoplatforms demonstrated selective uptake by MCF-7 breast cancer cells, negligible internalization in normal fibroblasts, and DNase-responsive drug release. Upon near-infrared irradiation, the dual-aptamer assemblies elicited rapid photothermal heating, elevated intracellular reactive oxygen species (ROS), and mitochondrial dysfunction, generating a potent synergistic chemo-photothermal cytotoxicity. DOX-loaded RA@QDs further inhibited cancer cell migration, highlighting the enhanced therapeutic efficacy. This modular nanoplatform integrates the programmable DNA architecture, precise molecular targeting, enzyme-responsive drug delivery, and efficient photothermal activation, providing a scalable and mechanistically unified strategy for precision cancer nanomedicine.
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ACS Applied Bio Materials
·
2026
·
IF 5.6
Qi Cai,Yue Li,Xuewei Ba,Piaoping Yang
The aberrant vascularization and uneven vascular distribution stemming from rapid tumor cell proliferation culminate arouse intra-tumoral hypoxia, which substantially compromises the therapeutic response to conventional chemotherapy, as well as photothermal therapy (PTT) and photodynamic therapy (PDT). In this work, we present an innovative α-NaYbF4:Tm@Cu2-xSe@ZnFe2O4-DOX nanoplatform that synergistically integrates PTT, Fenton reaction-enhanced chemodynamic therapy, PDT, and doxorubicin (DOX)-based chemotherapy under 980 nm near-infrared (NIR) light activation and weakly acidic environment-initiation. The 10 nm cubic-phase α-NaYbF4:Tm up-conversion cores were initially synthesized. Subsequently, low atomic number (Z) Cu2-xSe nanocrystal grown as photo-thermal conversion agent demonstrated significantly stronger X-radiation (X-ray) attenuation capabilities and enhanced computed tomography (CT) imaging performance compared to clinically used iopromide. Furthermore, zinc ferrite (ZnFe2O4) shell was obtained in hydrothermal synthesis manner. The 980 nm NIR-excited α-NaYbF4:Tm nanoparticles undergo efficient energy down-conversion, emitting photons that perfectly match the absorption spectrum of ZnFe2O4, thereby maximizing reactive oxygen species (ROS) generation through bandgap-engineered photoconversion. The tumor's glycolytic activity creates a hydrogen peroxide (H2O2)-rich microenvironment, enabling ZnFe2O4-mediated Fenton-like reactions that produce hydroxyl radicals (•OH) radicals, ultimately triggering oxidative damage and apoptotic cell death. It is noted that dual-mode photothermal therapeutic efficacy was achieved by Cu2-xSe and ZnFe2O4 as photothermal nanocrystal with up-conversion luminescence (UCL), magnetic resonance imaging (MRI) and CT multimodal imaging. DOX as anticancer chemotherapeutics was conjugated to form α-NaYbF4:Tm@Cu2-xSe@ZnFe2O4-DOX nanoplatforms. It remains effectively release of large quantities of DOX at tumor part conferred response to excessive lactic and carbonic acids generated in cancer cells. Our research may provide an insight for generalizing enhanced synergetic performance by NIR light-mediated PTT, Fenton reaction, PDT and chemotherapy. It is not a simple assembly of known components, but rather a multi-functional synergistic system constructed through ingenious core-shell structural design, capable of responding to near-infrared light and the tumor microenvironment. For the first time, this system seamlessly integrates up-conversion luminescence-mediated PDT, dual photothermal agent-enhanced PTT, self-supplying H2O2 Fenton reactions, and acid/heat dual-responsive chemotherapy into a single nanoplatform. Additionally, it incorporates multimodal imaging capabilities, providing an innovative and comprehensive solution to overcome the clinical challenge of tumor hypoxia.
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高影响因子
CARBOHYDRATE POLYMERS
·
2018
·
IF 5.158
Jiagen Li,Peng Liu
Facile one-pot approach was established to fabricate chitosan-based supramolecular nanogels as pH/reduction dual-stimuli responsive drug delivery system (DDS) for anticancer drug (doxorubicin, DOX), by bioreducible crosslinking of the β -cyclodextrin modified chitosan (CD-CS) with disulfide bond embedded crosslinker (Ad-SS-Ad) via host-guest inclusion and simultaneous DOX loading. The DOX@Ad-SS-Ad/CD-CS supramolecular nanogels with hydrodynamic diameter ( D h ) of 140 nm and drug-loading capacity of 15.9% were obtained with the mass feeding ratio of carrier:DOX at 25:10. They were stable in the simulated physiological medium with premature drug release of only 3% over 60 h, while a high cumulative release up to 82.3% was achieved within 84 h in a sustained manner without initial burst in the simulated tumor intracellular micro-environment. The MTT assays indicated that the blank Ad-SS-Ad/CD-CS supramolecular nanogels were cytocompatible, while the proposed DOX@Ad-SS-Ad/CD-CS supramolecular nanogels possessed the enhanced antitumor efficacy in comparison with the free DOX.
研究领域:
药剂学
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生物材料
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肿瘤学
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PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2021
·
IF 6.53
Jinzhi Xu,Yan Xu,Lixin Sun,Bei Lu,Xi Yan,Zhonghao Wang,Tong Zhang
Introduction The development of multidrug resistance (MDR) is a major cause for the failure of chemotherapy, which requires the aid of nanomedicine. Methods Here in our study, a Cu 2+ based metal-organic framework (COF) was firstly developed and employed as a carrier for the delivery of glucose oxidase (GOx) and doxorubicin (Dox) (COF/GOx/Dox) for the therapy of MDR lung cancers. Results Our results showed that the GOx can catalyze glucose and produce H 2 O 2 . In the mean time, the Cu 2+ can react with GSH and then transform into Cu + , which resulted in GSH depletion. Afterwards, the produced Cu + and H 2 O 2 trigger Fenton reaction to generate ROS to damage the redox equilibrium of cancer cells. Both effects contributed to the reverse of MDR in A549/Dox cells and finally resulted in significantly enhanced in vitro/in vivo anticancer performance. Discussion The combination of glutathione depletion/reactive oxygen species elevation might be a promising strategy to enhance the efficacy of chemotherapy and reverse MDR in cancers.
研究领域:
纳米医学
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癌症治疗
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药学科学
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生物化学
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PubMed
高影响因子
RSC Advances
·
2022
·Vol. 12
·期 30
·19063-19071
·
IF 4.036
Yehong Liu,Miaoxin Chen,Gaoyang Li,Shouhong Xu,Honglai Liu
In this study, a pH/reduction dual responsive carrier containing 42nt-nucleic acid HApt based on mesoporous silica nanoparticles (MSNs) was designed. Two kinds of low molecular weight oligomeric hyaluronic acid (HA) were used to graft onto MSN for better drug encapsulation. Crosslinked MSN-HA3000gel and MSN-HA11000gel were prepared by crosslinking the HA chain through the sulfhydrylization of the carboxyl group on the HA side chain. An appropriate amount of sulfhydryl nucleic acid (HApt-SH) was added during the crosslinking reaction, which realized the targeting ability and apoptosis function to cancer cells overexpressing the HER2 receptor. Crosslinked HA had a good effect on decreasing the side effect of DOX that the drug leakage was less than 20% under a normal body environment. However, it could realize rapid and efficient drug release in a tumor environment. As to the release of HApt, it exhibited a good response to GSH. The cytotoxicity test showed that HApt contained in HAgel had a great targeting effect and significant cytotoxicity to SKBR3 cells. As a whole, this MSN-HAgel enabled the combination of gene therapy and chemotherapy, showing the synergistic effect of “1 + 1 > 2”, providing a novel idea for cancer treatments.
研究领域:
纳米技术
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药学
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癌症研究
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生物医学工程
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2020
·
IF 4.321
Lan Cui,Xiayi Feng,Wentao Liu,Hao Liu,Qian Qin,Shuangxia Wu,Suqin He,Xinchang Pang,Dong Men,Chengshen Zhu
The surface charge of nanocarriers inevitably affects drug delivery efficiency; however, the cancer cell specificity, anti-inflammatory effects, and charge-reversal points remain to be further addressed in biomedical applications. The aim of this study was to comprehensively assess the cancer cell specificity of DOX-loaded mesoporous silica-chitosan oligosaccharide-carboxymethyl chitosan nanoparticles (DOX@MSNs-COS-CMC) in MCF-7 and HeLa cells, inhibit the production of inflammatory cytokines, and improve the drug accumulation in the tumor site. Intracellular results reveal that the retention time prolonged to 48 h in both HeLa and MCF-7 cells at pH 7.4. However, DOX@MSNs-COS-CMC exhibited a cell type-dependent cytotoxicity and enhanced intracellular uptake in HeLa cells at pH 6.5, due to the clathrin-mediated endocytosis and macropinocytosis in HeLa cells in comparison with the vesicular transport in MCF-7 cells. Moreover, Pearson’s correlation coefficient value significantly decreased to 0.25 after 8 h, prompting endosomal escape and drug delivery into the HeLa nucleus. After the treatment of MSNs-COS-CMC at 200 μg/mL, the inflammatory cytokines IL-6 and TNF-α level decreased by 70% and 80%, respectively. Tumor inhibition of DOX@MSNs-COS-CMC was 0.4 times higher than free DOX, alleviating cardiotoxicity and inflammation in the HeLa xenograft tumor model. Charge-reversible DOX@MSNs-COS-CMC could be a possible candidate for clinical therapy of cervical carcinoma.
研究领域:
药理学
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肿瘤学
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生物医学工程
·
纳米技术
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DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 9
·3652-3661
·
IF 5.251
Yunyan Li,Tong Yan,Wenya Chang,Chongjiang Cao,Dawei Deng
Cancer metastasis is a major cause of high mortality in breast cancer. Despite the progress achieved in nanomaterial-based treatments, the cure rate remains unsatisfactory, owing to their poor biocompatibility and non-specific recognition. Inspired by the cell-mimetic strategy, in this work, we fabricated an intelligent cell-like nano-prodrug (Dox-MPK@MDL) for lung metastasis of breast cancer. Specifically, a DNA tetrahedron dendrimer was selected to act as a rigid internal cytoskeleton, and then sequentially coated with a liposome and macrophage membrane to form cell-like Dox-MPK@MDL via hierarchical self-assembly. Here, it should be noted that pH-sensitive Dox-MPK prodrugs were synthesized and inserted into the DNA-based cytoskeleton (the Dox group is an intercalator of double stranded DNA) in advance for the next anti-metastatic therapy. Our results show that Dox-MPK@MDL specifically targeted the sites of lung metastasis via the biomimetic metastasis-homing effects and intelligently triggered Dox release at the metastatic cancer cells, thereby leading to the significant inhibition of lung metastasis. All these features help to enhance the anti-metastatic therapy efficiency of Dox while maximally reducing side-effects.
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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药物科学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Guiqiang Qi,Guangyue Shi,Shengchao Wang,Haifeng Hu,Zhichen Zhang,Qiangqiang Yin,Zhongtao Li,Liguo Hao
Introduction This study developed a pancreatic cancer targeted drug delivery system that responds to changes in acidity. The system was based on iron oxide core-shell magnetic mesoporous silica nanoparticles (M-MSNs) to treat pancreatic cancer through combined chemotherapy and starvation therapy.Methods Glucose oxidase (Gox) was coupled to the cancer cell surface to reduce glucose availability for cancer cells, exacerbating the heterogeneity of the tumor microenvironment. Reduced pH accelerated the depolymerization of pH-sensitive polydopamine (PDA), thereby controlling the spatial distribution of Gox and release of doxorubicin (DOX) within tumor cells.Results Characterization results showed the successful synthesis of DG@M-MSN-PDA-PEG-FA (DG@NPs) with a diameter of 66.02 ± 3.6 nm. In vitro data indicated DG@NPs were highly effective and stable with good cellular uptake shown by confocal laser scanning microscopy (CLSM). DG@NPs exhibited high cytotoxicity and induced apoptosis. Additionally, in vivo experiments confirmed DG@NPs effectively inhibited tumor growth in nude mice with good biosafety. The combination of starvation therapy and chemotherapy facilitated drug release, suggesting DG@NPs as a novel drug delivery system for pancreatic cancer treatment.Conclusion This study successfully constructed a doxorubicin release system responsive to acidity changes for targeted delivery in pancreatic cancer, providing a new strategy for combination therapy.
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高影响因子
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