Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 27
·5478-5489
·
IF 4.726
Yong Sun,Yaning Wang,Yani Cui,Wen Zou,Yanfei Tan,Jie Liang,Yujiang Fan,Xingdong Zhang
Stimuli-responsive targeted polymeric micelles as drug delivery systems have recently attracted significant attention for the treatment of various cancers, which could improve delivery efficiency by tumor-specific recognition via active targeting strategies. In this research, DOX-incorporated bioreducible polymeric micelles based on PAA-g-PEG/PEG–Fa conjugated polymers were prepared and characterized as nanocarriers for promoting intracellular anti-tumor drug delivery efficiency via folate receptor-mediated endocytosis. The anti-proliferative activity on cancer cells, biodistribution, active-/passive-targeting efficiency, tumor growth inhibition efficiency, and biological toxicity were evaluated in vitro and in vivo. The MTT assay demonstrated that the DOX-encapsulated active-targeting PAA-g-PEG/PEG–Fa micelles had much greater growth inhibition effect against 4T1 and KB than passive-targeting micelles. These active-targeting micelles showed superior tumor accumulation and excellent tumor growth inhibition effect as revealed by the fluorescence optical imaging technique and tumor volume change investigation, as well as the survival study of the tumor-bearing Balb/c mice. Furthermore, the active targeting micelles greatly decreased the toxicity of DOX on the heart and other organs. These potential results encouraged us to further optimize the molecular structure to achieve more excellent targeted therapeutic effect.
研究领域:
药剂学
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肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Yao Huang,Zhenluan Xue,Songjun Zeng
The development of stimuli-responsive multifunctional nanocarriers for therapeutic drug delivery is extremely desirable for highly specific treatment of disease. Herein, thiol–polyethylene glycol–folate acid-modified hollow mesoporous bismuth nanoshells (HM-Bi@PEG–FA NSs) were developed as the new dual-stimuli-responsive single-“elemental” photothermal nanocarriers for synergistic chemo-photothermal therapy of tumor. The designed hollow-mesoporous-type nanocarriers present excellent photothermal conversion capacity (∼34.72%) and good biocompatibility. Meanwhile, acidic pH and near-infrared (NIR) laser dual-stimulated doxorubicin (DOX) release is successfully achieved. More importantly, the DOX-loaded HM-Bi@PEG–FA NSs hold an efficient in vitro/in vivo antitumor effect through the synergistic chemo-photothermal therapy. Therefore, our findings provide the possibility of designing a dual-stimuli-responsive hollow mesoporous Bi-based photothermal nanocarrier for synergistically enhanced antitumor therapy.
研究领域:
纳米医学
·
癌症治疗
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2018
·
IF 4.525
Mingliang Pei,Xu Jia,Peng Liu
Theranostic nanomedicines for imaging guided therapy, simultaneously monitoring the real-time response of therapy, have aroused great interest in cancer research. Here, the Janus-like poly(methyl methacrylate)- b -poly(ethylene glycol)-folic acid block -copolymer-grafted fluorescent carbon dots (CDs-PMMA-PEG-FA) were synthesized via surface-initiated atom transfer radical polymerization (SI-ATRP) of methyl methacrylate (MMA) in ethanol with the modified carbon dots (CDs-Br) as initiator, followed by the PEGylation via click chemistry. Interestingly, they could self-assemble into blank nanoassemblies with hydrodynamic diameter of about 150 nm and Doxorubicin (DOX)-loaded nanoassemblies of about 270 nm with high DOX–loading capacity of 67.2%. The DOX-loaded nanoassemblies could release >80% of DOX at pH 5.0 within 36 h, while that at pH 7.4 was only 2%, demonstrating the excellent on-off behavior on pH stimuli. A possible mechanism was proposed to explore the drug release pathway in vitro. Enhanced anti-cancer efficacy of the CDs-PMMA-PEG-FA/DOX nanoassemblies with folate receptor (FR)-mediated targeting function than the free DOX was revealed by the MTT assays, while the bare CDs-PMMA-PEG-FA nanoassemblies possessed good cytocompatibility. The cellular uptake result showed that the proposed fluorescent theranostic nanomedicines could be effectively internalized into HepG2 cells and release DOX into the cell nuclei.
研究领域:
生物材料学
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纳米医学
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肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-15
·
IF 10.6
Sun Ying,Ma Yan-Yan,Shangguan Shijie,Ruan Yihang,Bai Tingjie,Xue Panpan,Zhuang Huilan,Cao Wenyu,Cai Huimei,Tang Enqi,Wu Zhou,Yang Mingzhen,Zeng Yixin,Sun Juan,Fan Yong,Zeng Xuemei,Yan Shuangqian
The activation of ferroptosis presents a versatile strategy for enhancing the antitumor immune responses in cancer therapy. However, developing ferroptosis inducers that combine high biocompatibility and therapeutic efficiency remains challenging. In this study, we propose a novel approach using biological nanoparticles derived from outer membrane vesicles (OMVs) of Escherichia coli for tumor treatment, aiming to activate ferroptosis and stimulate the immune responses. Specifically, we functionalize the OMVs by anchoring them with ferrous ions via electrostatic interactions and loading them with the STING agonist-4, followed by tumor-targeting DSPE-PEG-FA decoration, henceforth referred to as OMV/SaFeFA. The anchoring of ferrous ions endows the OMVs with peroxidase-like activity, capable of inducing cellular lipid peroxidation by catalyzing H 2 O 2 to • OH. Furthermore, OMV/SaFeFA exhibits pH-responsive release of ferrous ions and the agonist, along with tumor-targeting capabilities, enabling tumor-specific therapy while minimizing side effects. Notably, the concurrent activation of the STING pathway and ferroptosis elicits robust antitumor responses in colon tumor-bearing mouse models, leading to exceptional therapeutic efficacy and prolonged survival. Importantly, no acute toxicity was observed in mice receiving OMV/SaFeFA treatments, underscoring its potential for future tumor therapy and clinical translation.
研究领域:
癌症治疗
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纳米技术
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免疫疗法
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生物医学工程
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ChemPlusChem
·
2016
·Vol. 81
·期 11
·1237-1244
·
IF 2.836
Pei Zhang,Wenxiu He,Huiyuan Zhang,Chunzhi Huang,Dujuan Zhao,Yuxia Luan
Graphical Critical micelles concentrate on cancer : Mixed micelles made of a disulfide-linked drug–polymer conjugate and a polymer–folate conjugate were tested as a targeted, redox-sensitive delivery system (PEG–PBLG-SS-DTX/PEG–FA) for the anticancer drug docetaxel (DTX). The results showed improved anticancer efficiency of DTX delivered by these micelles to folate-receptor-expressing MCF-7 cancer cells. The objective of this study was to build mixed micelles based on two functional co-polymers, including the redox-sensitive polymer–drug conjugate methoxy poly(ethylene glycol)–poly(γ-benzyl l -glutamate)-disulfide-docetaxel (PEG–PBLG-SS-DTX) and the actively targeting methoxy poly(ethylene glycol)–folic acid (PEG–FA), for enhanced target specificity and improved anticancer efficiency of docetaxel (DTX). The spherical PEG–PBLG-SS-DTX/PEG–FA mixed micelles prepared by the dialysis method revealed a narrowly distributed size at 129.7±2.1 nm with low polydispersity of 0.10±0.02. Furthermore, the critical micelle concentration of the mixed micelles was 5.08 μg mL −1 , indicating excellent self-assembly ability in water and stability against dilution in blood circulation. The in vitro release study revealed that the conjugated DTX was rapidly released in response to dl -dithiothreitol (DTT), a reducing agent. Only 12.3 % of DTX was released from the mixed micelles after 120 h in the absence of DTT. However, the accumulative release of DTX dramatically accelerated and reached more than 40 % in 120 h after addition of DTT. The in vitro cytotoxicity, cellular uptake and cell apoptosis experiments on the mixed micelles were performed using MTT assay, fluorescence inverted microscopy and flow cytometric analysis, and 4′,6-diamidino-2-phenylindole (DAPI) staining, respectively, on folate receptor (FR)-negative A549 and FR-positive MCF-7 cells. The mixed micelles could be taken up efficiently by MCF-7 cells by FR-mediated endocytosis compared with PEG–PBLG-SS-DTX micelles. Furthermore, remarkable cytotoxicity and cell apoptosis were identified for the mixed micelles against MCF-7 cells, which was consistent with the results of the cellular uptake study. On the basis of these results, the redox-sensitive PEG–PBLG-SS-DTX/PEG–FA mixed micelles using FA as a targeting ligand revealed prominent antitumor efficiency and might be a latent drug carrier for cancer chemotherapy.
研究领域:
药学
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癌症研究
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纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2018
·
IF 5.08
Chunzhi Huang,Jilian Wu,Wei Jiang,Ruiling Liu,Zhonghao Li,Yuxia Luan
Graphene oxide (GO) has shown great potential in drug delivery. However, the aqueous stability, non-specific drug release and slow release rate are major problems of the GO-based drug delivery system. Herein, we for the first time integrate the dispersant, stabilizing agent and active targeting carrier into a novel drug delivery system based on GO/PP-SS-DOX nanohybrids. The redox-sensitive PP-SS-DOX prodrug was obtained by conjugating mPEG-PLGA (PP) with doxorubicin (DOX) via disulfide bond. PEG-FA provided active targeting property for the constructed drug delivery system, GO/PP-SS-DOX/PEG-FA. In this demonstrated system, PP-SS-DOX markedly increases the stability in physiological solutions of GO and guarantees the DOX release in the reductive environment (cancerous cells). And PEG-FA helps target to cancerous tissues and induces FR-mediated endocytosis. In vitro drug release exhibited the obvious reductive sensitivity and the cumulative release amount was up to 90%, while 40% in previous reports within 72 h. The in vitro cytotoxicity of targeting nanohybrids was significantly cytotoxic than that of non-targeting nanohybrids. In vivo results displayed that the as-prepared targeting nanohybrids showed efficacious antitumor effect while it had nearly no systemic adverse toxicity on B16 tumor-bearing mice. Therefore, the in vitro and in vivo results indicate that our constructed GO/PP-SS-DOX/PEG-FA drug delivery system is a promising carrier in cancer therapy.
研究领域:
药学
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纳米技术
·
癌症研究
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Ranxi Liang,Feize Li,Xijian Chen,Fuyuan Tan,Tu Lan,Jijun Yang,Jiali Liao,Yuanyou Yang,Ning Liu
Nano-metal–organic frameworks (nano-MOFs) labeled with radionuclides have shown great potential in the anticancer field. In this work, we proposed to combine fluorescence imaging (FI) with nuclear imaging to systematically evaluate the tumor inhibition of new nanomedicines from living cancer cells to the whole body, guiding the design and application of a high-performance anticancer radiopharmaceutical to glioma. An Fe-based nano-MOF vector, MIL-101(Fe)/PEG-FA, was decorated with fluorescent sulfo-cyanine7 (Cy7) to investigate the binding affinity of the targeting nanocarriers toward glioma cells in vitro, as well as possible administration modes for in vivo cancer therapy. Then, lutetium-177 (177Lu)-labeled MIL-101(Fe)/PEG-FA was prepared for high-sensitive imaging and targeted radiotherapy of glioma in vivo. It has been demonstrated that the obtained 177Lu-labeled MIL-101(Fe)/PEG-FA can work as a complementary probe to rectify the cancer binding affinity of the prepared nanocarrier given by fluorescence imaging, providing more precise biodistribution information. Besides, 177Lu-labeled MIL-101(Fe)/PEG-FA has excellent antitumor effect, leading to cell proliferation inhibition, upregulation of intracellular reactive oxygen species, tumor growth suppression, and immune response-related protein and cytokine upregulation. This work reveals that optical imaging and nuclear imaging can work complementarily as multimodal imaging in the design and evaluation of anticancer nanomedicine, offering a MIL-101(Fe)/PEG-FA-based pharmaceutical with potential in tumor endoradiotherapy.
研究领域:
纳米技术
·
放射学
·
肿瘤学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today
·
2023
·
IF 24.2
Xiao-Kang Jin,Jun-Long Liang,Shi-Man Zhang,Qian-Xiao Huang,Shun-Kang Zhang,Chuan-Jun Liu,Xian-Zheng Zhang
Owing to the deficiency of infiltrating immune cells and the accumulation of immunosuppressive cells in tumor microenvironment (TME), immunotherapy remains enormous challenges in colorectal cancer (CRC). Here, CRC was found to be sensitive to cuproptosis which could further evoke immune responses and mediate immune resistance. Thus, a cuproptosis-mediated immunotherapy nanoreactor (CCJD-FA) was constructed by encapsulating copper-based shell-coated CaO 2 and bromodomain-containing protein 4 inhibitor JQ-1 with DSPE-PEG-FA. Within tumor cells, CCJD-FA was disassembled under GSH environment, and the exposed CaO 2 could generate H 2 O 2 under the acidic condition, which reacted with the released Cu 2+ via Fenton-like reaction to produce O 2 for relieving hypoxia and Cu + for inducing cuproptosis. Furthermore, CCJD-FA could also inhibit intracellular glycolysis and ATP generation, then blocking the Cu + efflux protein ATP7B. Meanwhile, the IFN-γ-induced PD-L1 expression could be exactly reduced by the BRD4 suppression and oxygen supply. These effects sensitized cancer cells to cuproptosis, further evoking systemic immune responses and reshaping immunosuppressive TME to inhibit tumor growth.
研究领域:
肿瘤学
·
免疫学
·
纳米技术
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）