MEDICAL ONCOLOGY
·
2024
·Vol. 41
·期 5
·1-5
·
IF 2.8
Chen Jiejian,Li Yonghao,Gan Xiaoning,Weng Chengyin,Fang Xisheng,Liu Guolong
It has been proposed that boron neutron capture therapy (BNCT) holds promise as a treatment modality for melanoma. However, the effectiveness of boron agents in delivery remains a critical issue to be addressed for BNCT. To this end, phenylboronic acid, which exhibits good water solubility and low cytotoxicity similar to BPA, has been investigated as a potential nuclear-targeting boron agent. The boron concentration of phenylboronic acid was found to be 74.47 ± 12.17 ng/10 6 B16F10 cells and 45.77 ± 5.64 ng/10 6 cells in the nuclei. Molecular docking experiments were conducted to investigate the binding of phenylboronic acid to importin proteins involved in nuclear transport. The potential of phenylboronic acid to serve as a desirable nucleus-delivery boron agent for neutron capture therapy in melanoma warrants further exploration.
研究领域:
肿瘤学
·
药理学
·
核医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2016
·Vol. 8
·期 12
·6801-6809
·
IF 7.76
Lei Yang,Zheran Wang,Ju Wang,Weihua Jiang,Xuewei Jiang,Zhaoshi Bai,Yunpeng He,Jianqi Jiang,Dongkai Wang,Li Yang
Carbon dots (CDs) have shown great potential in imaging and drug/gene delivery applications. In this work, CDs functionalized with a nuclear localization signal peptide (NLS-CDs) were employed to transport doxorubicin (DOX) into cancer cells for enhanced antitumor activity. DOX was coupled to NLS-CDs (DOX-CDs) through an acid-labile hydrazone bond, which was cleavable in the weakly acidic intracellular compartments. The cytotoxicity of DOX-CD complexes was evaluated by the MTT assay and the cellular uptake was monitored using flow cytometry and confocal laser scanning microscopy. Cell imaging confirmed that DOX-CDs were mainly located in the nucleus. Furthermore, the complexes could efficiently induce apoptosis in human lung adenocarcinoma A549 cells. The in vivo therapeutic efficacy of DOX-CDs was investigated in an A549 xenograft nude mice model and the complexes exhibited an enhanced ability to inhibit tumor growth compared with free DOX. Thus, the DOX-CD conjugates may be exploited as promising drug delivery vehicles in cancer therapy.
研究领域:
药学
·
生物医学工程
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Yuanyuan Qin,Mengling Shen,Xinpei Liu,Jingyu Gu,Minqian Zhu,Xuan Yi
As a kind of high linear energy transfer (LET) radiation, internal conversion electrons are emitted from some radionuclides, such as 125I, triggering severe DNA damage to tumor cells when transported into the nucleus. Herein, we develop a curcumin-loaded nanomicelle composed of a photosensitizer chlorin e6 (Ce6) and amphiphilic poly(ethylene glycol) (poly(maleic anhydride-alt-1-octadecene)-poly(ethylene glycol) (C18-PMH-PEG)) to deliver 125I into the nucleus under 660 nm laser irradiation, leading to the optimized imaging-guided internal conversion electron therapy of cancer. Ce6-containing nanomicelles (Ce6-C18-PEG) self-assemble with nucleus-targeted curcumin (Cur), obtaining Ce6-C18-PEG/Cur nanoparticles. After labeling Cur with 125I, Ce6-C18-PEG/Cur enables single-photon emission computed tomography and fluorescence imaging of the tumor, serving as a guide for follow-up laser irradiation. Notably, the 660 nm laser-triggered photodynamic reaction of Ce6 optimizes the delivery of Ce6-C18-PEG/125I-Cur at various stages, including tumor accumulation, cellular uptake, and lysosome escape, causing plenty of 125I-Cur to enter the nucleus. By this strategy, Ce6-C18-PEG/125I-Cur showed optimal antitumor efficacy and high biosafety in mice treated with local 660 nm laser irradiation using efficient energy deposition of internally converted electrons over short distances. Therefore, our work provides a novel strategy to optimize 125I delivery for tumor treatment.
研究领域:
放射生物学
·
肿瘤学
·
纳米医学
✓ 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
·
肿瘤学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2021
·
IF 7.46
Hao Wu,Lan-Fang Pang,Na Wei,Xiao-Feng Guo,Hong Wang
We reported N-doped CDs (MTCDs) with excellent nucleus-targeted ability for selectively detecting ClO − . MTCDs can be easily prepared using m -phenylenediamine and 1,2,3-propanetricarboxylic acid as precursors through a solvothermal method. The maximum excitation/emission wavelengths were located at 444/513 nm, with QYs calculated to be 11.4 %. The fluorescence of MTCDs could be selectively quenched by ClO- upon the other ions, reactive oxygen species (ROS) and reactive nitrogen species (RNS). The quenching coefficient showed a good linearity versus C ClO - in the range of 1–100 μM, with detection limit of 0.48 μM. MTCDs were found to have splendid nuclear localization capabilities in MCF-7, Hela and H1299 cells and were successfully applied to image ClO − in cell nucleus and zebrafishes. During the nuclear localization mechanism study, we found a very interesting phenomenon: MTCDs were rare negatively charged CDs targeting nucleus by binding to the groove of DNA through hydrogen bond, which were different with most reported positively charged nucleus-targeted CDs via electrostatic adsorption. This finding proved that negatively charged CDs could also win the nucleus-targeted ability. Besides, this work provided a new strategy for designing nucleus-targeted CDs as well as the research of targeted release of drugs and cancer treatment.
研究领域:
生物化学
·
医学影像
·
药物设计
✓ 已验证
产品关联
DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2018
·
IF 5.08
Guan-Hai Wang,Hua Chen,Yin-Yu Cai,Li Li,Hui-Kang Yang,Qin Li,Zhi-Jiang He,Jian-Tao Lin
The nucleus is one of the most important cellular organelles, where gene encode and transcribe at that location. However, nucleus-targeting gene delivery are rare been reported. It is important to develop a high-efficiency nucleus-targeting gene vector that can deliver targeted gene into nucleus directly for destroy of cancer cells. Here, special nucleus-targeting and size changeable deliver system based on TAT-SS-PAMAM-D3 with TAT functional on the surface and disulfide linked between D2 and D3 is designed to perform highly efficient nucleus-targeting gene delivery for effective cancer cell killing in vitro. CLSM observations reveal that more TAT-SS-PAMAM-D3 are enter into the nucleus when compare to SS-PAMAM-D3. The TAT modified vector can also act as gene deliver to reach high gene transfection efficiencies, high apoptosis and low viability in HeLa cells. This TAT functionalized and disulfide linking in the carrier may become a prospective vector for cancer gene treatment and also offered a different strategy for designing a better gene delivery system.
研究领域:
遗传学
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2021
·Vol. 413
·期 13
·3493-3499
·
IF 4.157
Cao Xiuping,Shang Xinxin,Guo Yingshu,Zheng Xiaofei,Li Wenxin,Wu Di,Sun Li,Mu Shanliang,Guo Chuanen
In the process of drug carrier design, lysosome degradation in cells is often neglected, which makes a considerable number of drugs not play a role. Here, we have constructed a tumor treatment platform (Apn/siRNA/NLS/HA/Apt) with unique lysosomal escape function and excellent cancer treatment effect. Apoferritin (Apn) has attracted more and more attention because of its high uniformity, modifiability, and controllability. Meanwhile, its endogenous nature can avoid the risk of immune response being eliminated. We used aptamer modified iron deficient protein nanocages (Apn) to tightly encapsulate the combination of siRNA and NLS (siRNA/NLS) with influenza virus hemagglutinin (HA peptide). After Apn/siRNA/NLS/HA/Apt was targeted into cells, the acidic environment of lysosome led to the cleavage of Apn nanocages, and the release of siRNA/NLS and HA peptide. HA peptide can destroy lysosome membrane, make siRNA/NLS escape lysosome, and enter the nucleus under the action of NLS, resulting in efficient gene silencing effect. This kind of cancer treatment strategy based on Apn nanocage shows high biocompatibility and unique lysosome escape property, which significantly improves the drug delivery and treatment efficiency. Graphical abstract
Lysosomal escape protein nanocarriers for nuclear-targeted siRNA delivery
研究领域:
纳米医学
·
癌症生物学
·
药物递送系统
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Jian-Tao Lin,Hua Chen,Dan Wang,Liang Xiong,Jia-Zhu Li,Gui-hong Chen,Guang-Bin Chen
The nucleus is one of the most important cellular organelles. Chitosan-grafted poly-(N-3-carbobenzyloxy-lysine) (CCL) decorated with human immunodeficiency virus-1 transactivator of transcription (TAT) can co-deliver p53 and doxorubicin into the nucleus simultaneously, such that their antitumor functions are exerted. However, TAT-CCL has been shown to have an anti-tumor effect only in vitro; the effect in vivo was unsatisfactory. Here, a unique nucleus-targeted delivery system based on amidized TAT (aTAT)-CCL with aTAT functional on the surface was designed to achieve a highly efficient nucleus-targeting gene and drug delivery system for effective cancer cell elimination in vitro and in vivo. In this delivery system, TAT is amidized to inhibit its nonspecific interactions. Confocal laser scanning microscopy observations revealed that if aTAT-CCL was incubated in pH 5.0 acetate buffer solution for 24 h before use (named aTAT-CCL-HB), more aTAT-CCL-HB entered the nucleus compared with aTAT-CCL or CCL. aTAT-CCL-HB can also achieve high gene transfection and drug delivery efficiencies and low viability in HepG2 cells. However, only aTAT-CCL achieved extensive circulation in the blood compartment and high antitumor activity in vivo. Amidization of TAT in vectors may become a promising strategy for nucleus-targeted delivery systems, especially in in vivo applications.
研究领域:
癌症研究
·
药剂学
·
分子生物学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2014
·
IF 5.9
Ze-Yong Li,Yun Liu,Jing-Jing Hu,Qi Xu,Li-Han Liu,Hui-Zhen Jia,Wei-Hai Chen,Qi Lei,Lei Rong,Xian-Zheng Zhang
In this paper, a novel stepwise-acid-active multifunctional mesoporous silica nanoparticle (MSN-SATAT&DMAK11) was developed as a drug carrier. The MSN-SATAT&DMAK11 is able to reverse its surface charge from negative to positive in the mildly acidic tumor extracellular environment. Then, the fast endo/lysosomal escape and subsequent nucleus targeting as well as intranuclear drug release can be realized after cellular internalization. Because of the difference in acidity between the tumor extracellular environment and that of endo/lysosomes, this multifunctional MSN-SATAT&DMAK11 exhibits a stepwise-acid-active drug delivery with a tumor-specific nucleus-targeted property.
研究领域:
纳米医学
·
生物材料
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Ruihan Li,Xuan Yin,Chuanke Chong,Yan Li,Qingqiang Yao,Yanling Mu,Chunyu Zhang
Polypeptides as drug delivery vehicles can achieve the targeted therapeutic effects of first-line platinum drugs in clinical practice, providing an important method to solve problems such as the high systemic toxicity of first-line platinum drugs. In this work, we employ a rational molecular conjugation strategy to design and synthesize two platinum(IV) prodrugs. The first, s-CisPt(IV)-TAT, is linked to a single nuclear-targeting polypeptide, while the second, d-CisPt(IV)-TAT, is conjugated with two of these polypeptides. Interestingly, despite the higher degree of functionalization, disubstituted d-CisPt(IV)-TAT exhibits lower reactivity and cytotoxicity than its monosubstituted counterpart. This counterintuitive result suggests that overloading with multiple ligands may reduce cellular uptake, thereby compromising therapeutic efficacy. Furthermore, both constructs are shown to induce apoptosis via DNA damage pathways, confirming their mechanism of action. These results underscore the importance of precisely tuning the ligand density in drug carriers. Our work provides valuable insights into the structure–activity relationships governing platinum prodrugs and highlights the need for a balance between functional density and biological performance in the design of next-generation polypeptide-conjugated chemotherapeutics.
研究领域:
肿瘤学
·
药物化学
·
分子药理学
·
纳米医学
·
转化医学
·
生物材料
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2025
·Vol. 192
·期 9
·1-15
·
IF 5.3
Xue Boyang,Li Qiang,Xing Yanjiao,Mu Hongkai,Yang Yongzhen,Chen Lin,Yu Shiping,Guo Rongrong
To overcome the dual challenges of suboptimal therapeutic outcomes and delayed detection in hepatocellular carcinoma (HCC), a nucleus-targeting theranostic nanoplatform based on gadolinium-functionalized carbon dots (GdCDs) is presented. GdCDs were synthesized via a one-step hydrothermal method utilizing neutral red and citric acid as carbon precursors and gadolinium chloride hexahydrate as the paramagnetic source, showing good fluorescence (FL) and magnetic resonance imaging (MRI) capabilities. After modified with a nuclear localization sequence (NLS), GdCDs were loaded with doxorubicin (DOX) to yield the integrated theranostic platform: Nucleus-targeting gadolinium-functionalized carbon dot drug delivery system (NT-GdCDs-DDS) for FL/MRI dual-modality imaging and nucleus-targeting drug delivery. NT-GdCDs-DDS exhibited optimal excitation/emission wavelengths at 497/596 nm, a high longitudinal relaxivity (r 1 ) of 23.11 mM −1 s −1 , and a DOX loading efficiency of 61.9%. Results of antitumor activity assays in vitro demonstrated the viability of HepG2 cells incubated with 400 μg/mL NT-GdCDs-DDS for 24 h was 8.12%, demonstrating strong antitumor activity. Furthermore, a significant tumor growth suppression in mice was observed by treated with NT-GdCDs-DDS over a 15-day period, showing superiority to free DOX. These findings establish NT-GdCDs-DDS as a potent theranostic nanoplatform for simultaneous HCC imaging and therapy. Graphical abstract
研究领域:
纳米医学
·
肿瘤学
·
诊断成像
·
药物递送系统
·
生物工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2022
·Vol. 14
·期 39
·14645-14660
·
IF 8.307
Li-Min Zhai,Yan Zhao,Rui-Lin Xiao,Shi-Quan Zhang,Bao-Hua Tian,Xin-Xin Li,Rong Zhang,Ri-Sheng Ma,Hai-Xia Liang
Nuclear targeted delivery has great potential in improving the efficiency of non-viral carrier mediated genome editing. However, direct and efficient delivery of CRISPR/Cas9 plasmid into the nucleus remains a challenge. In this study, a nuclear targeted gene delivery platform based on fluorescent carbon quantum dots (CQDs) was developed. Polyethylenimine (PEI) and polyethylene glycol (PEG) synergistically passivated the surface of CQDs, providing an excitation-independent green-emitting fluorescent CQDs–PEI–PEG conjugate (CQDs–PP) with an ultra-small size and positive surface charge. Here we show that CQDs–PP could bind CRISPR/Cas9 plasmid to form a nano-complex by electrostatic attraction, which can bypass lysosomes and enter the nucleus by passive diffusion, and thereby improve the transfection efficiency. Also, CQDs–PP could deliver CRISPR/Cas9 plasmid into HeLa cells, resulting in the insertion/deletion mutation of the target EFHD1 gene. More importantly, CQDs–PP exhibited a considerably higher gene editing efficiency as well as comparable or lower cytotoxicity relative to Lipo2000 and PEI-passivated CQDs–PEI (CQDs–P). Thus, the nuclear-targeted CQDs–PP is expected to constitute an efficient CRISPR/Cas9 delivery carrier in vitro with imaging-trackable ability.
研究领域:
遗传学
·
分子生物学
·
生物医学工程
·
纳米技术
✓ 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）