ACS Nano
·
2022
·
IF 18.027
Jing-Jie Ye,Wuyang Yu,Bo-Ru Xie,Ke Li,Miao-Deng Liu,Xue Dong,Zhao-Xia Chen,Jun Feng,Xian-Zheng Zhang
Conventional cancer targeting methodology needs to be reformed to overcome the intrinsic barriers responsible for poor targeting efficiency. This study describes a concept of self-reinforced cancer targeting (SRCT) by correlating targeting with therapy in a reciprocally enhancing manner. SRCT is achieved on the basis of two prerequisites: (1) target molecules have to be expressed on cancer cell membranes but not on normal cells, and (2) notably, their expression on cancer cells must be actively upregulated in response to cellular attack by cancer treatments. As a proof-of-concept, a GRP78-targeting nanovehicle for chemotherapy was designed. Resultant data showed that chemotherapeutic drugs could effectively elevate GRP78 expression on the plasma membranes of cancer cells while having minimal influence on normal cells. DOX pretreatment of cancer cells and tumor tissues can greatly increase the targeting efficacy and therapeutic performance of the prepared GRP78-targeting nanomedicine while somewhat disfavoring the nontargeting counterpart. In vivo and in vitro results demonstrated that this GRP78-targeting nanomedicine could accurately target cancer cells to not only implement chemotherapy but also induce GRP78 upregulation on cancer cells, eventually benefiting continuous cancer-cell-targeted attack by the nanomedicines remaining in the blood circulation or administered in the next dose. The GRP78-targeting nanomedicine displays much better antitumor performance compared with the nontargeting counterpart. SRCT is expected to advance cancer-targeted therapy based on the positive dependency between targeting and therapeutic modalities.
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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DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2024
·
IF 7
Xialin Chen,Dandan Li,Rongrong He,Jiajia Wang,Ru Yang,Mengyu Qian,Liang Cao,Yongwen Zhang,Zhenzhong Wang,Wei Xiao
Polyrhachis dives ( P. dives ) is a traditional edible insect with high nutritional value and is the only ant species that is administered as medicine and food. Therefore, it is of great significance to identify the authenticity of the species. In the current study, peptidomics analysis combining untargeted MS with targeted MS was developed and applied for the identification of specific peptides in P. dives and the establishment of quality control. A total of 16 specific peptides were screened, and 7 specific peptides with satisfactory signal response were obtained by targeted mass spectrometry, which could be used to distinguish P. dives from other ant species and ensure the quality of edible ants. Subsequently, the 7 specific peptides were quantitatively analyzed, followed by clustering analysis and biological activity experiments to categorize them into distinct qualities, providing valuable references for further development of quality control methods for P. dives .
研究领域:
昆虫学
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食品科学
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质谱分析
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Demeng Xia,Qingqing Qian,Sheng Wang,Xiao Dong,Ying Liu
Introduction Osteoporosis, characterized by dysregulation of osteoclastic bone resorption and osteoblastic bone formation, severely threatens human health during aging. However, there is still no good therapy for osteoporosis, so this direction requires our continuous attention, and there is an urgent need for new drugs to solve this problem.Methods Traditional Chinese Medicine Salvia divinorum monomer pomolic acid (PA) could effectively inhibit osteoclastogenesis and ovariectomized osteoporosis. However, its poor solubility and lack of targeting severely limits its further application. A novel bone-targeting nanomedicine (PA@TLipo) has been developed to reconstruct the osteoporotic microenvironment by encapsulating pomolic acid in alendronate-functionalized liposomes. Through a series of operations such as synthesis, purification, encapsulation, and labeling, the PA@TLipo have been prepared. Moreover, the cytotoxicity, bone targeting and anti-osteoporosis effect was verified by cell and animal experiments.Results In the aspect of targeting, the PA@TLipo can effectively aggregate on the bone tissue to reduce bone loss, and in terms of toxicity, PA@TLipo could increase the bone target ability in comparison to nontargeted liposome, thereby mitigating systemic cytotoxicity. Moreover, PA@TLipo inhibited osteoclast formation and bone resorption in vitro and reduced bone loss in ovariectomy-induced osteoporotic mice.Conclusion In this study, a novel therapeutic agent was designed and constructed to treat osteoporosis, consisting of a liposome material as the drug pocket, PA as the anti-osteoporosis drug, and ALN as the bone-targeting molecule. And our study is the first to employ a bone-targeted delivery system to deliver PA for OVX-induced bone loss, providing an innovative solution for treating osteoporosis.
研究领域:
药理学
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骨生物学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2013
·Vol. 1
·期 46
·6402-6410
·
IF 0
Qi Zhang,Jundong Zhu,Lichao Song,Ju Zhang,Deling Kong,Yanjun Zhao,Zheng Wang
Nanoparticle drug delivery to tumors via the enhanced permeability and retention (EPR) effect is usually limited by the step of blood circulation and extravasation. Only less than 10% of the administered dose would eventually reach the tumor tissue. To enhance the drug delivery efficiency, we report the approach of magnetic plus molecular dual targeting nanoparticles to combine tumor targeting, drug delivery, and in situ imaging together. The surface of superparamagnetic iron oxide nanoparticles (SPIONs) was coated with biocompatible poly(ethylene glycol)–poly(lactic acid) and then anchored with folic acid (FA). Despite the presence of FA, the hydrodynamic size of SPIONs was less than 100 nm. Increasing the surface FA density sacrificed the aqueous stability of SPIONs, but 20% FA did not induce noticeable particle aggregation. The existence of 20% FA maintained the superparamagnetic property of SPIONs with a saturation magnetization level at ca. 30 emu g−1. The drug release profile was not significantly different between SPIONs with (20%) and without FA. However, the presence of FA dramatically increased the intracellular uptake of SPIONs when using the MCF-7 breast cancer cell line. These results highlighted the role of surface ligand optimization in the design of desired magnetic-molecular dual tumor-targeting nanoparticles.
研究领域:
生物医学工程
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药学
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纳米医学
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产品关联
DOI
PubMed
ANALYTICAL CHEMISTRY
·
2025
·
IF 6.7
Chang Liu,Jianguo Dong,Chunyan An,Dekun Wang,Xue Mi,Shijing Yue,Xiaoyue Tan,Yuying Zhang
Nanoparticles (NPs) exhibit great promise in cancer diagnosis and treatment as drug carriers, imaging probes, and therapeutic agents. The surface ligands of NPs play a crucial role in determining their accumulation at the tumor site, thereby affecting the overall theranostic effectiveness. Here, we report a precise technique for the direct comparison of NP deposition within a singular tumor model by surface-enhanced Raman spectroscopy (SERS) encoding. We synthesized SERS-encoded NPs functionalized with diverse ligands (PEG for passive targeting and APTMUC1 or iRGD for active targeting, respectively) and administered a 1:1:1 mixture of the NPs to monolayer-cultured T47D breast cancer cells, 3D multicellular spheroids, and xenograft tumor-bearing mice. Through simultaneous localization and quantification of different NPs in the same tumor cell/spheroid/tissue section, we found that APTMUC1 incorporation could effectively enhance NP delivery in vitro (7.2× and 4.1× for T47D cells and spheroids, respectively, in comparison to the PEGylated NPs), albeit the active targeting efficacy was compromised for in vivo tumor delivery (1.4×). Modification with iRGD facilitated NP delivery with a lower efficiency (2.9×, 1.7×, and 1.1× for T47D cells, spheroids, and tumor tissue, respectively). The findings illustrate the effectiveness of employing the active targeting approach yet underscore the necessity for additional optimization of the NPs to surmount biological barriers in vivo despite successful active targeting observed in vitro. Moreover, this multicolor SERS-encoding technique can be further utilized to systematically explore the spatial distribution of NPs with diverse physiochemical attributes among different tissues and organs.
研究领域:
纳米技术
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癌症研究
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生物成像
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药物递送
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分析化学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Mingzhu Xie,Jing Zhao,Xiaokai Feng,Xu Gao,Wenwen Cheng,Lingheng Kong,Fei Liang
Conventional chemotherapy is challenged by its inherent limitations. As an emerging drug delivery system, nanoparticles are easily eliminated by the immune system due to their exogenous nature. Moreover, the lack of long-circulation and tumor-targeting greatly limits their application. In our research, to address this problem, the biomimetic nanocarriers combine cell membranes, targeting ligand and nanoparticles into one system. Firstly, an active ester monomer and three terpolymers PMAN containing different proportions of phosphorylcholine, sulfonic acid and active ester group were successfully synthesized. Subsequently, aminated-folate was synthesized and grafted onto the terpolymers to prepare the folate-targeted polymers FA-PMAN. Finally, cell membrane biomimetic and folate-targeted chitosan nanoparticles (FA-PMAN/CS) with average particle size of 100 to 200 nm were prepared through electrostatic interactions. The in vivo blood circulation results showed that the long-circulating properties of PMAN/CS nanoparticles were significantly enhanced, compared with TPP/CS nanoparticle as a control. The half-life extended from 2.71 h to 12.95 h, with five-fold increase. Additionally, the uptake efficiency of FA-PMAN/CS nanoparticles by rat breast cancer cells (MADB-106) was 5–6 times greater than that of nanoparticles without folate. The biological distribution in mice demonstrated that the signal intensity in tumors treated with FA-PMAN/CS nanoparticle was substantially higher than in other organs, indicating that folate on the surface of nanoparticles increased the uptake into cancer cells. This work aims to design more efficient nanocarriers through biomimetic simulation of cell membranes, reduce recognition and clearance by the immune system, prolong blood circulation time and achieve tumor-targeted drug delivery. It is expected to significantly improve efficacy and provide an innovative strategy for clinical treatment.
研究领域:
药剂学
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生物医学工程
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ORGANIC & BIOMOLECULAR CHEMISTRY
·
2017
·Vol. 15
·期 27
·5764-5771
·
IF 3.564
Sizhe Zhu,Si Yao,Fengshou Wu,Lijun Jiang,Ka-Leung Wong,Ji Zhou,Kai Wang
Organelle and nucleus dual-targeted anticancer drugs are being increasingly used for efficient cancer therapy as they can attack the double vital sites of tumor cells. In this work, we synthesized and characterized two new porphyrin compounds Pt-Por-RB and Me-Por-RB. The spectral titration results suggest that both Pt-Por-RB and Me-Por-RB bind to DNA efficiently in an intercalation binding mode. Upon irradiation, Pt-Por-RB with low dark-cytotoxicity can rapidly generate singlet oxygen to damage the tumor cells through the process of photodynamic therapy. Compared with Me-Por-RB, Pt-Por-RB was not only internalized in the organelles, but also in the nuclei of HeLa cells, probably due to the presence of platinum complexes, as analyzed using the confocal laser scanning microscope. Thus, with the combination of organelle and nucleus dual-targeting property and high efficiency of singlet oxygen generation, Pt-Por-RB showed a significant therapeutic activity against tumor cells.
研究领域:
药理学
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肿瘤学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Peng Zhong,Xiaoqun Wei,Yi Xu,Lulu Zhang,Anastasios Koidis,Yunle Liu,Yi Lei,Shaozong Wu,Hongtao Lei
In this work, an untargeted and pseudotargeted metabolomics combination approach was used for authentication of three shrimp species (Litopenaeus vanmamei, Penaeus japonicus, and Penaeus monodon). The monophasic extraction-based untargeted metabolomics approach enabled comprehensive-coverage and high-throughput analysis of shrimp tissue and revealed 26 potential markers. The pseudotargeted metabolomics approach confirmed 21 markers (including 9 key markers), which realized at least putative identification. The 21 confirmed markers, as well as 9 key markers, were used to develop PLS-DA models, correctly classifying 60/60 testing samples. Furthermore, DD-SIMCA and PLS-DA models were integrated based on the 9 key markers, with 59/60 and 20/20 samples of the species that were involved and uninvolved in model training correctly classified. The results demonstrated the potential of this untargeted and pseudotargeted metabolomics combination approach for shrimp species authentication.
研究领域:
食品科学
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代谢组学
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生物化学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Chao Liu,Yuhao Jiang,Wenliang Xue,Jinyu Liu,Zihao Wang,Jianhong Luo,Xinsong Li
Lipid nanoparticles (LNP) have shown great promise in clinical applications for delivering mRNA. Targeted delivery of mRNA to particular tissues or organs is essential for precise therapeutic outcomes and minimized side effects in various disease models. However, achieving targeted delivery beyond the liver is a challenge based on current LNP formulations. In this report, we synthesized four ionizable cholesterol analogs by attaching two tertiary amine groups onto the head of a cholesterol-like structure and incorporated them as a fifth component into conventional commercial LNPs based on ALC-0315 or SM-102. Selective targeting delivery of mRNA is achieved by adjusting the proportion of the fifth component in the LNP. Specifically, a spleen-targeted 0315-Ergo-40% formulation demonstrated an impressive 95% delivery efficiency, while a lung-targeted 102-Sito-40% formulation achieved up to 78%. Moreover, when this strategy is applied to a self-developed ionizable lipid named U-101 instead of ALC-0315 or SM-102, the targeting delivery efficiencies to the spleen and lungs reach 96 and 71%, respectively. Multiple assessments suggest that inclusion of the fifth component does not compromise LNP stability, as indicated by consistent particle size, polydispersity index (PDI), and encapsulation efficiency. Furthermore, the test results of liver and kidney function and immunogenicity reveal no increase of toxicity in vivo following the introduction of the fifth component. Additional studies on in vitro cytotoxicity, lysosomal escape, and cellular transfection efficiency confirm that the fifth component does not diminish delivery performance. Taken together, the incorporation of ionizable cholesterol analogs leads to targeting of LNP delivery, which features strong organ selectivity, high safety, and suitability for further evaluation.
研究领域:
纳米技术
·
药学科学
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分子生物学
·
治疗学
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2018
·Vol. 6
·期 11
·2998-3008
·
IF 5.831
Jieming Li,Yan Liu,Huilan Li,Wei Shi,Xinzhou Bi,Qianqian Qiu,Bo Zhang,Wenlong Huang,Hai Qian
Subcellular organelle-specific reagents for simultaneous tumor targeting, imaging, and treatment are of enormous interest in cancer therapy. Herein, we present a mitochondria targeting micelle (PEG-AIE-TPP) by conjugating a triphenylphosphonium (TPP) with a fluorogen which can undergo aggregation-induced emission (AIE). At first, the in vitro and in vivo properties of the PEG-AIE-TPP micelle were characterized in detail. It was found that the micelle was reasonably stable at physiological pH and highly sensitive to mildly acidic pH stimuli. Importantly, this micelle could selectively localize and accumulate in the mitochondria, thus generating an aggregation-induced emission (AIE) effect as confirmed by the green fluorescence. Additionally, the micelle exhibited selective cytotoxicity to cancer cells and negligible toxicity to normal cells in vitro. The in vivo imaging and ex vivo imaging results showed that the accumulation tendency of the micelle at the tumor region was obvious. We also further proved the biocompatible, tumor targeting ability and antitumor activity of the PEG-AIE-TPP micelle in MCF-7 tumor-bearing mice. Accordingly, this mitochondria-targeted therapeutic micelle with good stability, biocompatibility, and tumor-targeting and antitumor activity provides a potentially unique tumor-targeted system for cancer therapy.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2019
·
IF 6.361
Junqiang Zhao,Caixia Yan,Ze Chen,Jinjian Liu,Huijuan Song,Weiwei Wang,Jianfeng Liu,Ning Yang,Yiping Zhao,Li Chen
Multifunctional nanoparticles (NPs) with high blood-stability, tumor-targeting ability, and stimuli-bioresponsive drug release behaviors are urgently demanded. Herein, folic acid (FA) and galactose (GAL) functionalized, core-crosslinked NPs (CC NPs) with dual-targeting and pH/redox-bioresponsive properties were developed based on amphiphilic FA-poly(6-O-methacryloyl- d -galactopyranose)- b -poly[2-(diisopropylamino) ethyl methacrylate- co -pyridyl disulfide methylacrylate] [FA-PMAgGP- b -P(DPA- co -PDEMA), termed as FA-PMgDP] block copolymers , and then investigated for facilitated hepatoma-targeting delivery of doxorubicin (DOX). A series of PMgDP copolymers were synthesized though two-step RAFT copolymerization followed by acid-induced acetal deprotection reaction. Their well-defined chemical structures and compositions were characterized by 1 H NMR and gel permeation chromatography . Nano-sized, non-crosslinked PMgDP NPs (PMgDP NC NPs) with sizes of less than 25 nm in aqueous solution were self-assembled via the solvent exchange method, and PMgDP CC NPs were readily prepared in the presence of dithiothreitol. The drug-loading content of PMgDP CC NPs was up to 15.8% and its entrapment efficiency was 89.0%. In normal physiological conditions, 11.6% of DOX was released from DOX-loaded PMgDP CC NPs at 25 h, whereas in analogous intracellular microenvironment, 95.5% was released at 11 h owing to the acid-induced protonation of tertiary amine and reductive cleavage of disulfide bond in the hydrophobic core. In a cellular uptake study, FA and GAL-mediated, active, dual-targeted DOX-loaded FA-PMgDP CC NPs showed a 3.54-fold increase in cellular uptake efficiency to HepG2 cells compared to that of shown by single GAL-targeted, DOX-loaded PMgDP NC NPs. Results of in vitro cytotoxicity study showed that blank FA-PMgDP CC NPs exhibited good biocompatibility, whereas dual-targeting DOX-loaded FA-PMgDP CC NPs increased cell apoptosis. Therefore, the above results indicated that the well-constructed FA-PMgDP CC NPs with multi-synergistic effect may serve as new nanocarriers in the field of precise hepatoma-targeting drug delivery.
研究领域:
药剂学
·
肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2013
·Vol. 5
·期 24
·12409-12424
·
IF 6.233
Haiyan Chen,Bowen Li,Jiadan Qiu,Jiangyu Li,Jing Jin,Shuhang Dai,Yuxiang Ma,Yueqing Gu
Two kinds of thermally responsive polymers P(FAA-NIPA-co-AAm-co-ODA) and P(FPA-NIPA-co-AAm-co-ODA) containing folate, isopropyl acrylamide and octadecyl acrylate were fabricated through free radical random copolymerization for targeted drug delivery. Then the micelles formed in aqueous solution by self-assembly and were characterized in terms of particle size, lower critical solution temperature (LCST) and a variety of optical spectra. MTT assays demonstrated the low cytotoxicity of the control micelle and drug-loaded micelle on A549 cells and Bel 7402 cells. Then fluorescein and cypate were used as model drugs to optimize the constituents of micelles for drug entrapment efficiency and investigate the release kinetics of micelles in vitro. The FA and thermal co-mediated tumor-targeting efficiency of the two kinds of micelles were verified and compared in detail at cell level and animal level, respectively. These results indicated that the dual-targeting micelles are promising drug delivery systems for tumor-targeting therapy.
研究领域:
药剂学
·
肿瘤学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）