Journal of Materials Chemistry B
·
2021
·Vol. 10
·期 3
·438-449
·
IF 6.331
Qiusheng Wang,Ziyun He,Hai Zhu,Wenxia Gao,Nan Zhang,Jing Li,Jianqin Yan,Bin He,Xueting Ye
A peptide/DNA nanocomplex was developed for the targeted delivery of chemotherapeutics and photosensitizers to cancer cells for efficient combination therapy. The chemotherapeutic drug doxorubicin (DOX) and the photosensitizer 5,10,15,20-tetra-(1-methylpyridine-4-yl)-porphyrin (TMPyP4) were physically incorporated by an aptamer (AS1411)-modified tetrahedral DNA nanostructure, where the tetrahedral DNA and aptamer-induced G-quadruplex provide binding sites of DOX and TMPyP4. The co-loaded 3A-TDN/DT displayed a targeted uptake by HeLa cancer cells through the high affinity and specificity between AS1411 and nucleolin, a protein overexpressed on many types of cancer cells. A polycationic polymer, mPEG-PAsp(TECH), was synthesized to complex with the DNA nanostructure to efficiently escape from lysosomes via the proton sponge effect upon the enhanced internalization by tumor cells. Under the irradiation of 660 nm laser light, TMPyP4 induced an upregulation of intracellular reactive oxygen species, which combined with DOX to fulfill the efficient inhibition of HeLa cells. Our study demonstrated a biocompatible peptide/DNA composite nanoplatform for combinational cancer therapy via the targeted delivery of therapeutic agents and efficient lysosomal escape.
研究领域:
癌症治疗
·
纳米技术
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药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2014
·
IF 7.261
Beilu Zhang,Zhong Luo,Junjie Liu,Xingwei Ding,Jinghua Li,Kaiyong Cai
To develop carriers for efficient anti-cancer drug delivery with reduced side effects, a biocompatible and redox-responsive nanocontainer based on mesoporous silica nanoparticles (MSNs) for tumor-targeted triplex therapy was reported in this study. The nanocontainer was fabricated by immobilizing cytochrome c (CytC) onto the MSNs as sealing agent via intermediate linkers of disulfide bonds for redox-responsive intracellular drug delivery . AS1411 aptamer was further tailored onto MSNs for cell/tumor targeting. The successful construction of redox- responsive MSNs was confirmed by BET/BJH analysis, transmission electron microscopy , Fourier transform infrared spectroscopy , fluorescence spectroscopy and thermogravimetric analysis (TGA), respectively. Detailed investigations demonstrated that anticancer drug of doxorubicin (DOX) loaded nanocontainer could be triggered by reductant ( e.g. glutathione) within cellular microenvironment and release DOX to induce tumor cell apoptosis in vitro . More importantly, the nanocontainer displayed great potential for tumor targeting and achieved triplex therapy effects on the tumor inhibition in vivo through the loading DOX, gatekeeper of CytC and AS1411 aptamer, which were reflected by the change of tumor size, TUNEL staining and HE staining assays.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2022
·
IF 6.633
Danfeng Wang,Min Liu,Yushu Wu,Tianxin Weng,Lu Wang,Yongfang Zhang,Yanna Zhao,Jun Han
The co-loading of chemotherapy-phototherapy (CTPT) combination drugs by aptamer-targeted DNA nanostructures has significant advantages in improving anticancer effects and overcoming the multidrug resistance of cancer cells. The different binding modes of drugs to DNA nanostructures may impact CTPT therapy. Here, the anti-drug resistance effects of idarubicin (IDA) or acridine orange (AO) as single drug, as well as IDA/mithramycin (MTR) dimers ((MTR) 2 Zn 2+ ) + AO combination drugs loaded by AS1411-tethered DNA nanotrains (AS1411NTrs), were studied. The intercalative binding mode between IDA/AO and AS1411NTrs was verified through measurements of viscosity, changes in melting temperature, and potassium iodide quenching. A series of thermodynamic parameters such as the binding constant and the number of binding sites were obtained through fluorescence spectroscopy, isothermal titration calorimetry, and differential scanning calorimetry. The high binding constants and the number of binding sites indicated that AS1411NTrs had a high loading capacity for IDA and AO. An in vitro release study showed that the release rate and release model of IDA/(MTR) 2 Zn 2+ /AO in the binary and ternary systems with or without deoxyribonuclease I were related to their binding mode and order of addition. An in vitro cytotoxicity study proved that the cytotoxicity and synergistic effects of the three drugs to human breast cancer MCF-7 cells and multidrug-resistant MCF-7/ADR cells were enhanced due to loading of AS1411NTrs. The IDA/(MTR) 2 Zn 2+ + AO combination drugs could more obviously enhance apoptosis of MCF-7/ADR cells as confirmed by cell apoptosis assays. The cell uptake study demonstrated that IDA/(MTR) 2 Zn 2+ /AO loaded by AS1411NTrs was mainly concentrated in the nucleus of MCF-7/ADR cells. This work will provide theoretical information for combination therapy of IDA/(MTR) 2 Zn 2+ and AO based on DNA nanostructures.
研究领域:
药学
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纳米技术
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癌症研究
·
生物物理学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-14
·
IF 10.2
Li Mengyue,Yang Geng,Zheng Yue,Lv Jiazhen,Zhou Wanyi,Zhang Hanxi,You Fengming,Wu Chunhui,Yang Hong,Liu Yiyao
Targeted chemo-phototherapy has received widespread attention in cancer treatment for its advantages in reducing the side effects of chemotherapeutics and improving therapeutic effects. However, safe and efficient targeted-delivery of therapeutic agents remains a major obstacle. Herein, we successfully constructed an AS1411-functionalized triangle DNA origami (TOA) to codeliver chemotherapeutic drug (doxorubicin, DOX) and a photosensitizer (indocyanine green, ICG), denoted as TOADI (DOX/ICG-loaded TOA), for targeted synergistic chemo-phototherapy. In vitro studies show that AS1411 as an aptamer of nucleolin efficiently enhances the nanocarrier’s endocytosis more than 3 times by tumor cells highly expressing nucleolin. Subsequently, TOADI controllably releases the DOX into the nucleus through the photothermal effect of ICG triggered by near-infrared (NIR) laser irradiation, and the acidic environment of lysosomes/endosomes facilitates the release. The downregulated Bcl-2 and upregulated Bax, Cyt c, and cleaved caspase-3 indicate that the synergistic chemo-phototherapeutic effect of TOADI induces the apoptosis of 4T1 cells, causing ~ 80% cell death. In 4T1 tumor-bearing mice, TOADI exhibits 2.5-fold targeted accumulation in tumor region than TODI without AS1411, and 4-fold higher than free ICG, demonstrating its excellent tumor targeting ability in vivo. With the synergetic treatment of DOX and ICG, TOADI shows a significant therapeutic effect of ~ 90% inhibition of tumor growth with negligible systemic toxicity. In addition, TOADI presents outstanding superiority in fluorescence and photothermal imaging. Taken together, this multifunctional DNA origami-based nanosystem with the advantages of specific tumor targeting and controllable drug release provides a new strategy for enhanced cancer therapy.
研究领域:
癌症治疗
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纳米技术
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生物医学工程
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分子生物学
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药学
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成像技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2023
·
IF 8.2
Wenxin Zhang,Xiaodie Li,Jialin Zeng,Xin Wen,Chao Zhang,Yinan Zhang,Jian He,Lihua Yang
Radiation therapy (RT) has emerged as one of the most promising anti-tumor strategies for neuroblastoma. Nevertheless, the special tumor microenvironment (TME), including hypoxic and GSH-overexpressed TME, often greatly restricts the RT outcome. In this study, we demonstrated a dual-channel parallel radicals nanoamplifier (ATO@PAE-PEG-AS1411/Fe 3+ ). The nanoamplifier was shaped into a bilayer shell-core structure, in which atovaquone-loaded poly (β-amino esters)-poly (ethylene glycol) (ATO@PAE-PEG) served as the core while Fe 3+ -absorbed AS1411 aptamer (AS1411/Fe 3+ ) served as the shell. Taking advantage of the targeting ability of AS1411, ATO@PAE-PEG-AS1411/Fe 3+ specifically accumulated in tumor cells, and then released ATO as well as Fe 3+ in response to the acidic TME. The released ATO dramatically inhibited the mitochondrial respiration of tumor cells, thus sparing vast amounts of oxygen for the generation of free radicals during RT process, which was the first free radicals-amplifying pathway Meanwhile, the released Fe 3+ could consume the tumor-overexpressed GSH through the redox reaction, thus effectively preserving the generated free radicals in RT process, which was the second free radicals-amplifying pathway. Taken together, our study demonstrates a dual-channel parallel free radicals-amplifying RT strategy, and it is expected this work will promote the clinical application prospects of RT treatment against neuroblastoma.
研究领域:
肿瘤学
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纳米技术
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放射治疗
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药学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yunlong Wang,Jie Zhou,Yan Dong,Peng Wang,Ruiyang Zi,Honglan Zhang,Yingqiang Luo,Yan Zhang,Teng Wang,Yuhan Chen,Biao Hu,Houjie Liang,Zhihao Wei,Xiang Zhao
Constructing precise delivery systems to enhance the antitumor efficacy of drugs represents a pressing clinical practice need. The characteristics of suitable physiological stability, flexible tunable size, and highly programmable architecture make functional DNA scaffolds an ideal solution to this requirement. Here, we designed DNA oligonucleotide probes Y 1 , Y 2 and Y 3 to construct a smart-responsive Y-shaped DNA scaffold drug conjugate (sYDD). This sYDD incorporates two AS1411 aptamers, an apurinic/apyrimidinic (AP) site, a B-cell lymphoma-2 (Bcl-2) antisense oligonucleotide (ASO) and a doxorubicin (DOX)-carrying sequence. The Bcl-2 ASO and DOX within sYDD could be responsively released in tumor cells that exhibited high expression of apurinic/apyrimidinic endonuclease 1 (APE1) and microRNA-21 (miR-21). And the in vitro and in vivo experiments demonstrated that sYDD exhibited substantial antitumor efficiency. Moreover, the flow cytometry and RNA sequencing results proved that the proposed sYDD effectively activated immune responses. This strategy provides an alternative approach for designing synergistic chemo-gene drug conjugates, which facilitates the development of precision tumor treatment modalities.
研究领域:
药学
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生物技术
·
癌症研究
·
分子生物学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-20
·
IF 10.6
Li Tan,Zhang Xingyu,Shi Chengyu,Liu Qiao,Zhao Yuetao
Combination of tumor immunotherapy with photothermal therapy (PTT) is a feasible tactic to overcome the drawback of immunotherapy such as poor immune response. Via triggering the immunogenic cells death (ICD), PTT can stimulate the activity of immune cells, but meanwhile, the level of adenosine is elevated via the CD73-induced decomposition of ATP which is overexpressed accompanying with the PTT process, resulting in negative feedback to impair the immune stimulation. Herein, we developed a novel biomimetic photothermal nanodrug to specifically block CD73 for inhibition of adenosine production and more efficient priming of the suppressive immune microenvironments. The nanodrug, named as AptEM@CBA, is constructed by encapsulation of photothermal agent black phosphorus quantum dots (BPQDs) and selective CD73 inhibitor α, β-Methyleneadenosine 5′-diphosphate (AMPCP) in chitosan nanogels, which are further covered with aptamer AS1411 modified erythrocyte membrane (EM) for biomimetic camouflage. With AS1411 induced active targeting and EM induced long blood circulation time, the enrichment of the nanodrug tumor sites is promoted. The photothermal treatment promotes the maturation of dendritic cells. Meanwhile, the release of AMPCP suppress the adenosine generation via CD73 blockade, alleviating the impairment of adenosine to dendritic cells and suppressing regulatory T cells, synergically stimulate the activity of T cells. The combination of CD73 blockade with PTT, not only suppresses the growth of primary implanted tumors, but also boosts strong antitumor immunity to inhibit the growth of distal tumors, providing good potential for tumor photoimmunotherapy.
研究领域:
纳米技术
·
癌症免疫治疗
·
光热疗法
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Weicai Wang,Yuanyuan Wang,Minghui Ma,Hyung Jong Jin,Xuemei Li
The construction of completely biocompatible and biodegradable tumor suppressors by a simple and reliable method is essential for the clinical application of cancer-targeted drugs. Herein, by inserting glucose oxidase (GOx), catalase (CAT), and chlorin e6 (Ce6) into human serum albumin (HSA) assembly molecules, we constructed a cancer-targeted cascade bioreactor for synergistic starvation and photodynamic therapy (PDT). The modification of HSA could block the GOx activity and reduce the cytotoxicity of normal cells and organs. Through active targeting and passive enhanced permeability and retention effect, the loading of AS1411 could promote the cascade bioreactors to effectively target nucleolin-overexpressed tumors. Once internalized by cancer cells, as a result of catalyzing hydrogen peroxide (H2O2) to produce oxygen (O2), the protein nano-cascade reactor promoted microenvironmental oxygenation, which would subsequently lead to an increase in cytotoxic singlet oxygen (1O2) production under light irradiation as well as the decomposition of intracellular glucose. In vitro and in vivo studies showed that the cascaded nanoreactors could significantly enhance therapeutic efficacy through synergistic starvation therapy and enhanced PDT as well as chemotherapy. This cascade strategy will be demonstrated in clinical applications with huge potential.
研究领域:
癌症研究
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2022
·Vol. 32
·期 17
·2108883
·
IF 19.924
Xiu Zhao,Kaixiang Zhang,Yiyang Wang,Wenxiao Jiang,Hui Cheng,Qiongwei Wang,Tingting Xiang,Zhenzhong Zhang,Junjie Liu,Jinjin Shi
Efficient nuclear DNA damage and release is highly recommended to improve the photodynamic immunotherapy by eliciting innate immune response yet remains challenging. Herein, an intracellular self-assembly driven nucleus-targeted photo-immune stimulator (PIS) with chromatin decompaction function is reported for innate and adaptive antitumor immunity co-activation. The PIS consists of vorinostat (SAHA)-loaded manganese-porphyrin metal-organic framework (Mn (III)-TCPP MOF) with further modification of AS1411 aptamer. The PIS can be efficiently internalized by tumor cells and disassembled under the intracellular overexpressed glutathione (GSH). Notably, the released AS1411 is able to be self-assembled with photosensitizer TCPP in situ within cells, driving nucleus-targeted delivery of TCPP; meanwhile, the loaded SAHA can induce chromatin decompaction, cooperatively promoting TCPP-mediated photodynamic nuclear DNA damage and cytosolic release under laser irradiation. In addition, the released manganese ions (Mn 2+ ) further enhance the cytosolic DNA/cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) pathway mediated innate immunity, which synergizes with PDT-induced immunogenic cell death to achieve co-activation of innate and adaptive immunity. Compared to traditional PDT, the self-assembly driven nucleus-targeted PDT system with chromatin decompaction show significantly enhanced efficacy for inhibiting primary tumor growth and distant metastasis in several xenograft tumor models, mechanistically by promoting the maturation of dendritic cells and tumor infiltration of natural killer cell, cytotoxic T lymphocytes.
研究领域:
癌症研究
·
免疫学
·
药学
·
纳米技术
·
生物医学工程
✓ 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）