BIOMATERIALS
·
2024
·
IF 12.8
Min Gao,Qiuting Sun,Ruijie Zhang,Guisong Shan,Huiru Zhang,Rui Peng,Mengyu Liu,Gengyun Sun,Lei Qiao,Yang Li,Xiaoyan He
Developing drug delivery systems capable of achieving deep tumor penetration is a challenging task, yet there is a significant demand for such systems in cancer treatment. Hitchhiking on tumor-derived extracellular vesicles (EVs) represents a promising strategy for enhancing drug penetration into tumors. However, the limited drug assembly on EVs restricts its further application. Here, we present a novel approach to efficiently attach antitumor drugs to EVs using an engineered cell membrane-based vector. This vector includes the AS1411 aptamer for tumor-specific targeting, the vesicular stomatitis virus glycoprotein (VSV-G) for tumor cell membrane fusion, and a photosensitizer as the therapeutic agent while ensuring optimal drug encapsulation and stability. Upon injection, photosensitizers are firstly transferred to the tumor cell membrane and subsequently piggybacked onto EVs with the inherent secretion process. By hitchhiking with EVs, photosensitizers can be transferred layer by layer deep into the solid tumors. The results suggest that this EVs-hitchhiking strategy enables photosensitizers to penetrate deeply into tumor tissue, thereby enhancing the efficacy of phototherapy. This study offers broad application prospects for delivering drugs deeply into tumor tissues.
研究领域:
药学
·
癌症研究
·
生物技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2018
·
IF 4.37
Yang Li,Yanhong Duo,Jiangang Bi,Xiaowei Zeng,Lin Mei,Shiyun Bao,Lisheng He,Aijun Shan,Yue Zhang,Xiaofang Yu
Introduction MicroRNA-155 (miR-155) is an oncogenic microRNA, which is upregulated in many human cancers including colorectal cancer (CRC). Overexpression of miR-155 has been found to regulate several cancer-related pathways, and therefore, targeting miR-155 may be an effective strategy for cancer therapy. However, effective and safe delivery of anti-miR-155 to tumors remains challenging for the clinical applications of anti-miR-155-based therapeutics. Methods In this study, we explored the expression of miR-155 and the transcription factor nuclear factor kappa B (NF-κB) in CRC tissues and cell lines, and the possible relationship between miR-155 and NF-κB. We further report on anti-miR-155-loaded mesoporous silica nanoparticles (MSNs) modified with polymerized dopamine (PDA) and AS1411 aptamer (MSNs-anti-miR-155@PDA-Apt) for the targeted treatment of CRC. Results Results showed that miR-155 is overexpressed in CRC tissues and cell lines, and there is a positive feedback loop between NF-κB and miR-155. Compared to the control groups, MSNs-anti-miR-155@PDA-Apt could efficiently downregulate miR-155 expression in SW480 cells and achieve significantly high targeting efficiency and enhanced therapeutic effects in both in vivo and in vitro experiments. Furthermore, inhibition of miR-155 by MSNs-anti-miR-155@PDA-Apt can enhance the sensitivity of SW480 to 5-fluorouracil chemotherapy. Conclusion Thus, our results suggested that MSNs-anti-miR-155@PDA-Apt is a promising nanoformulation for CRC treatment.
研究领域:
肿瘤学
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纳米技术
·
分子生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2017
·
IF 4.44
Shudi Yang,Zhaoxiang Ren,Mengtian Chen,Ying Wang,Bengang You,Weiliang Chen,Chenxi Qu,Yang Liu,Xuenong Zhang
In this article, a novel graft polymeric micelle with targeting function ground on aptamer AS1411 was synthesized. The micelle was based on chitosan-ss-polyethylenimine-urocanic acid (CPU) with dual pH/redox sensitivity and targeting effects. This micelle was produced for codelivering Toll-like receptor 4 siRNA (TLR4–siRNA) and doxorubicin (Dox). In vitro investigation revealed the sustained gene and drug release from Dox–siRNA-loaded micelles under physiological conditions, and this codelivery nanosystem exhibited high dual pH/redox sensitivity, rapid intracellular drug release, and improved cytotoxicity against A549 cells in vitro. Furthermore, the micelles loaded with TLR4–siRNA inhibited the migration and invasion of A549. Excellent tumor penetrating efficacy was also noted in the A549 tumor spheroids and solid tumor slices. In vivo, multiple results demonstrated the excellent tumor-targeting ability of AS1411-chitosan-ss-polyethylenimine-urocanic acid (ACPU) micelle in tumor tissues. The micelles exhibited excellent antitumor efficacy and low toxicity in the systemic circulation in lung-tumor-bearing BALB/c mice. These results conclusively demonstrated the great potential of the new graft copolymer micelle with targeting function for the targeted and efficient codelivery of chemotherapeutic drugs and genes in cancer treatment.
研究领域:
药学
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生物医学工程
·
癌症研究
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药物递送系统
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Chuan Hu,Jiaqi Ma,Ziye Su,Junyu Wang,Xueqian Zhang,Lin Pang,Yan Qu,Jinfeng Shi,Jinming Zhang
The combination of doxorubicin (Dox) and glycyrrhetinic acid (GA) has been widely explored for treating various cancers, while the heterogeneous distribution, uncontrolled release and acid tumor microenvironment often hinder their synergistic effects. Herein, we introduce an acid/glutathione (GSH)-dual responsive nano-prodrug (AS1411@Dox + GA/NPs) enabling precise co-delivery of Dox and GA for enhanced combination therapy. The GSH-activated Dox prodrug [Poly(lactic- co -glycolic acid)-disulfide-Dox, PLGA-ss-Dox], GA, and sulfur-terminated D-α-tocopherol polyethylene glycol succinate (TPGS-SH) are combined to form a nanoemulsion with sodium bicarbonate (NaHCO 3 ) in the aqueous phase. The AS1411 aptamer is modified on the surface for tumor-specific targeting. Upon reaching the tumor via enhanced penetration and retention effects, AS1411 aptamer medicates specific endocytosis of AS1411@Dox + GA/NPs into tumor cells. Intracellularly, the acidic endosomal environment promotes carbon dioxide (CO 2 ) production from NaHCO 3 , disrupting the nanoemulsion and causing a burst release of GA and PLGA-ss-Dox prodrug. Concurrently, high levels of GSH in the cytoplasm triggers the cleavage of the disulfide linker, thereby releasing Dox. Notably, the released NaHCO 3 consumed hydrogen ion (H + ), amplifying the sensitivity of tumor cells to Dox. As a consequence, AS1411@Dox + GA/NPs exhibits remarkable synergistic therapeutic efficacy on both liver cancer and breast cancer bearing mouse models. This work presents an appealing approach utilizing stimuli-sensitive nano-prodrug for advanced combinational cancer treatment.
研究领域:
药学
·
肿瘤学
·
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 Today Bio
·
2024
·
IF 8.7
Hongjian Liao,Yuchao Cao,Can Hu,Shangfeng Shen,Zhifei Zhang,Dairong Li,Yonghong Du
Lung cancer is the deadliest kind of cancer in the world, and the hypoxic tumor microenvironment can significantly lower the sensitivity of chemotherapeutic drugs and limit the efficacy of different therapeutic approaches. In order to overcome these problems, we have designed a drug-loaded targeted DNA nanoflowers encoding AS1411 aptamer and encapsulating chemotherapeutic drug doxorubicin and oxygen-producing drug horseradish peroxidase (DOX/HRP-DFs). These nanoflowers can release drugs in response to acidic tumor microenvironment and alleviate tumor tissue hypoxia, enhancing the therapeutic effects of chemotherapy synergistic with sonodynamic therapy. Owing to the encoded drug-loading sequence, the doxorubicin loading rate of DNA nanoflowers reached 73.24 ± 3.45%, and the drug could be released quickly by disintegrating in an acidic environment. Furthermore, the AS1411 aptamer endowed DNA nanoflowers with exceptional tumor targeting properties, which increased the concentration of chemotherapeutic drug doxorubicin in tumor cells. It is noteworthy that both in vitro and in vivo experiments demonstrated DNA nanoflowers could considerably improve the hypoxia of tumor cells, which enabled the generation of sufficient reactive oxygen species in combination with ultrasound, significantly enhancing the therapeutic effect of sonodynamic therapy and evidently inhibiting tumor growth and metastasis. Overall, this DNA nanoflowers delivery system offers a promising approach for treating lung cancer.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2021
·
IF 6.057
Yu-Bin Su,Xu Zhao,Li-Jian Chen,Hai-Long Qian,Xiu-Ping Yan
Photodynamic therapy (PDT) received great attention in cancer therapy due to the advantages of negligible drug resistance, low side effects, and minimal invasiveness. Development of theranostic nanoprobes with specific imaging-guided PDT is of great significance in the field. Herein we report the fabrication of a novel theranostic nanoprobe porphyrin/G-quadruplex conjugated gold/persistent luminescence nanocomposites for imaging-guided PDT. The developed nanoprobe contains NIR-emitting persistent luminescent nanoparticles (PLNP) as the core for autofluorescence-free bioimaging and Au coating on PLNP for facile subsequent DNA conjugation. The DNA sequence is designed to contain G-rich AS1411 aptamer for recognizing the over-expressed cellular nucleolin of cancer cell and forming a G-quadruplex structure to combine with tetrakis (4-carboxyphenyl) porphyrin (TCPP) to realize PDT. The AS1411 aptamer-contained DNA conjugated Au-coated PLNP is rapidly prepared via a freezing method with high content of DNA and good aqueous stability. Meanwhile, TCPP is easily loaded into the G-quadruplex structure formed from G-rich AS1411 aptamer on the surface of Au/PLNP in presence of K + . The theranostic nanoprobe gives integrated merits of PLNP for autofluorescence-free bioimging, TCPP for PDT and AS1411 aptamer-contained DNA for specific binding to cancer cells. This work provides a new specially designed imaging-guided PDT nanoplatform for theranostics.
研究领域:
纳米医学
·
癌症治疗
·
分子影像
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2016
·
IF 8.387
Dan Chen,Bowen Li,Songhua Cai,Peng Wang,Shuwen Peng,Yuanzhi Sheng,Yuanyuan He,Yueqing Gu,Haiyan Chen
Dual targeting towards both extracellular and intracellular receptors specific to tumor is a significant approach for cancer diagnosis and therapy. In the present study, a novel nano-platform (AuNC-cRGD-Apt) with dual targeting function was initially established by conjugating gold nanocluster (AuNC) with cyclic RGD (cRGD) that is specific to α v β 3 integrins over-expressed on the surface of tumor tissues and aptamer AS1411 (Apt) that is of high affinity to nucleolin over-expressed in the cytoplasm and nucleus of tumor cells. Then, AuNC-cRGD-Apt was further functionalized with near infrared (NIR) fluorescence dye (MPA), giving a NIR fluorescent dual-targeting probe AuNC-MPA-cRGD-Apt. AuNC-MPA-cRGD-Apt displays low cytotoxicity and favorable tumor-targeting capability at both in vitro and in vivo level, suggesting its clinical potential for tumor imaging. Additionally, Doxorubicin (DOX), a widely used clinical chemotherapeutic drug that kill cancer cells by intercalating DNA in cellular nucleus, was immobilized onto AuNC-cRGD-Apt forming a pro-drug, AuNC-DOX-cRGD-Apt. The enhanced tumor affinity, deep tumor penetration and improved anti-tumor activity of this pro-drug were demonstrated in different tumor cell lines, tumor spheroid and tumor-bearing mouse models. Results in this study suggest not only the prospect of non-toxic AuNC modified with two targeting ligands for tumor targeted imaging, but also confirm the promising future of dual targeting AuNC as a core for the design of prodrug in the field of cancer therapy.
研究领域:
纳米技术
·
癌症生物学
·
药物科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Jinzhe Liang,Yanting Yang,Yanni Luo,Lixian Huang,Shulin Zhao
Elevating photothermal conversion efficiency (PCE) is the key to enhance curative efficacy during photothermal therapy. Nevertheless, current functionalized or synthetic methods for preparing photothermal agents with high PCE are too complicated, greatly hindering the development of photothermal therapy. In this study, we developed a tumor-targeting flower-like nanocomposite termed mesoporous platinum nanoparticles@Cu 2- x Se-AS1411 (MPNPs@Cu 2- x Se-AS1411, denoted as MPCSA) with remarkable PCE for high-resolution photoacoustic (PA) imaging guided photothermal/chemodynamic therapy for tumor ablation. We discovered that MPNPs served as carriers for delivering PA contrast agents. Cu 2- x Se nanosheets emerged as promising near-infrared-II (NIR-II) PA imaging and photothermal/chemodynamic therapy agents owing to their strong localized surface plasmon resonance property in the NIR-II region. The amine-modified AS1411 aptamer, which is connected to the surface of the flower-like MPNPs@Cu 2- x Se can target the nucleolar protein on the surface of 4T1 cells, achieving the accumulation of MPCSA at the tumor site in mice. Notably, these MPCSA nano-flowers exhibited an excellent PCE up to 82.33 % under 1064 nm laser irradiation, resulting in highly efficient cancer cell ablation and greatly hindering in vivo tumor growth. This study has paved the way for imaging-guided accurate cancer diagnosis and targeted cancer therapy.
研究领域:
材料科学
·
纳米技术
·
生物医学工程
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癌症研究
·
诊疗学
✓ 已验证
产品关联
DOI
高影响因子
ANALYTICA CHIMICA ACTA
·
2020
·
IF 5.977
Yaqin He,Caizhi Lv,Xiandeng Hou,Lan Wu
Taking advantage of the superior biocompatibility, good stability in a wide pH and temperature range, as well as its strong affinity with DNA of hydroxyapatite (HAp), tetrahedral DNA nanostructures (TDNs) conjugated with AS1411 aptamer ( anti -nucleolin overexpressed on tumor cell membranes) were employed as affinity ligands to construct a novel mono-dispersed HAp based probe with Gd 3+ doping (Apt-TDNs-GdHAp) for MR imaging. The adsorption of TDNs on the nano-HAp surface facilely accomplished the construction of the Apt-TDNs-GdHAp probes. Meanwhile, the use of hydrophilic TDNs not only favored the phase-transfer from the oil phase to the aqueous phase, but also enhanced the mono-dispersion of this probe due to the well-ordered distribution of TDNs on the surface of nano-HAp. Moreover, Apt-TDNs-GdHAp probe with a better mono-dispersion and crystalinity achieved twice higher longitudinal relaxivity (r 1 value) than that of GdHAp synthesized by microwave-assisted method (Microwave-GdHAp), exhibiting much more excellent T 1 -weighted imaging performance. With the introduction of TDNs, the stability and the tumor-targeting accessibility were also greatly improved, showing its great potential for further bio-applications.
研究领域:
纳米技术
·
生物医学工程
·
分子生物学
·
材料科学
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医学成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYST
·
2019
·Vol. 145
·期 3
·836-843
·
IF 4.019
Yong Wang,Lulu Cai,Qi Wang,Mingming Zhao,Lina Dong,Kai Xu,Jingjing Li
Transition-metal dichalcogenides (TMDCs) have attracted a lot of attention due to their electronic, optical, mechanical, and catalytic properties. In addition, TMDCs possess rich redox chemistry that enables the decoration of metal nanoparticles directly on their surfaces. In this paper, MnO2/MoS2 nanocomplexes were obtained by the spontaneous reduction of KMnO4 with MoS2 QDs as the reductive agent. The formed MnO2/MoS2 nanocomplexes exhibited activated fluorescence and MR imaging signal in the presence of glutathione (GSH). After conjugation with an AS1411 aptamer, specific in vivo MR imaging and fluorescence labeling of the 786-O tumor cells were realized, showing their promising potential for biomedical applications.
研究领域:
材料科学
·
纳米技术
·
生物医学工程
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2022
·
IF 5.763
He Ziyun,Wang Qiusheng,Zhang Nan,Yan Jianqin,Li Li,Cao Jun,He Bin
Combination therapy is extensively developed for cancer treatment in recent years due to its high efficiency. Herein, we constructed a nanocomposite based on gold nanorods (GNRs) and drug-loaded tetrahedral DNA nanostructures (TDN) for chemo-photothermal combinational therapy. Anti-tumor drug doxorubicin (DOX) was loaded via the insertion within GC base pairs of TDN. The aptamer AS1411 was attached to the apex of TDN (ATDN) to target tumor cells. The DOX-loaded DNA tetrahedron (ATDN-DOX) was compressed by the GNRs coated with PEI (GNRs@ATDN-DOX) to realize the photothermal function and lysosome escape. GNRs under the illumination of 808 nm infrared laser showed high photothermal conversion and stability due to the protection of PEI layer. The drug-loading capacity of ATDN-DOX was as high as 314 DOX molecules in per ATDN. The positive charge of PEI in GNRs@ATDN-DOX nanocomposites was utilized to achieve excellent cell penetration and induce proton sponge effect for lysosomal escape. The nanocomposites presented HeLa and 4T1 cells targeting and resulted in efficient anticancer activity.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Zhengyue Kang,Min Yang,Xiaoling Feng,Hongjian Liao,Zhifei Zhang,Yonghong Du
Purpose Triple negative breast cancer (TNBC) is challenging for effective remission due to its very aggressive, extremely metastatic and resistant to conventional chemotherapy. Herein, a multifunctional theranostic nanoparticle was fabricated to enhance tumor targeted imaging and promote focused ultrasound (FUS) ablation and chemotherapy and sonodynamic therapy (SDT). A multi-modal synergistic therapy can improve the therapeutic efficacy and prognosis of TNBC.Methods AS1411 aptamer modified PEG@PLGA nanoparticles encapsulated with perfluorohexane (PFH) and anti-cancer drug doxorubicin (DOX) were constructed (AS1411-DOX/PFH-PEG@PLGA) to enhance tumor targeted imaging to guide ablation and synergistic effect of FUS/chemotherapy. FUS was utilized to trigger the co-release of doxorubicin and simultaneously PFH phase transition and activate DOX for SDT effect. The physicochemical, phase-changeable imaging capability, biosafety of nanoparticles and multi-mode synergistic effects on growth of TNBC were thoroughly evaluated in vivo and in vitro.Results The synthesized AS1411-DOX/PFH-PEG@PLGA (A-DPPs) nanoparticles are uniformly round with an average diameter of 306.03 ± 5.35 nm and the zeta potential of −4.05 ± 0.13 mV, displaying high biosafety and FUS-responsive drug release in vitro and in vivo. AS1411 modified NPs specifically bind to 4T1 cells and elevate the ultrasound contrast agent (UCA) image contrast intensity via PFH phase-transition after FUS exposure. Moreover, the combined treatment of A-DPPs nanoparticles with FUS exhibited significantly higher apoptosis rate, stronger inhibitory effect on 4T1 cell invasion in vitro, induced more reactive oxygen species (ROS), and enhanced anti-tumor effect compared to a single therapy (p < 0.05). Additionally, the joint strategy resulted in more intense cavitation effect and larger ablated areas and reduced energy efficiency factor (EEF) both in vitro and in vivo.Conclusion The multifunctional AS1411-DOX/PFH-PEG@PLGA nanoparticles can perform as a marvelous synergistic agent for enhanced FUS/chemotherapy, promote real-time contrast enhanced US imaging and improve the therapeutic efficacy and prognosis of TNBC.
研究领域:
肿瘤学
·
纳米技术
·
医学影像
·
癌症治疗
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）