Journal of Materials Chemistry B
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2013
·Vol. 1
·期 46
·6402-6410
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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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DOI
PubMed
Scientific Reports
·
2018
·Vol. 8
·期 1
·1-18
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IF 4.122
Du Jing,Li Xiao-Yu,Hu He,Xu Li,Yang Shi-Ping,Li Feng-Hua
Molecularly-targeted contrast enhanced ultrasound (US) imaging is a promising imaging strategy with large potential for improving diagnostic accuracy of conventional US imaging in breast cancer detection. Therefore, we constructed a novel dual-targeted nanosized US contrast agent (UCA) directed at both vascular endothelial growth factor receptor 2 (VEGFR2) and human epidermal growth factor receptor 2 (HER2) based on perfluoropropane (C 3 F 8 )-filled poly(lactic-co-glycolic acid) (PLGA) (NBs) for breast cancer detection. In vitro , single- or dual-targeted PLGA NBs showed high target specificities and better effects of target enhancement in VEGFR2 or HER2-positive cells. In vivo , US imaging signal in the murine breast cancer model was significantly higher ( P < 0.01) for dual-targeted NBs than single-targeted and non-targeted NBs. Small animal fluorescence imaging further confirmed the special affinity of the dual-targeted nanosized contrast agent to both VEGFR2 and HER2. Immunofluorescence and immunohistochemistry staining confirmed the expressions of VEGFR2 and HER2 on tumor neovasculature and tumor cells of breast cancer. In conclusions, the feasibility of using dual-targeted PLGA NBs to enhance ultrasonic images is demonstrated in vitro and in vivo . This may be a promising approach to target biomarkers of breast cancer for two site-specific US molecular imaging.
研究领域:
医学影像
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肿瘤学
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药剂学
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生物医学工程
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DOI
PubMed
高影响因子
ADVANCES IN POLYMER TECHNOLOGY
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2020
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IF 1.539
Jinjing Xing,Yeqiang Cai,Yikun Wang,Haifu Zheng,Yujia Liu
CaCO3 nanoparticles are very suitable as intelligent carriers because of their ideal biocompatibility and biodegradability, especially their sensitivity to pH. In this paper, we use mesoporous CaCO3 nanoparticles as intelligent carrier, sodium alginate, and chitosan as alternating assembly materials, folic acid as target molecules, and exploit layer-by-layer assembly technology to achieve sensitive molecular targeting and pH response drug release. Mesoporous CaCO3 hybrid nanoparticles have high drug loading on doxorubicin. The effects of different pH values on drug release in vitro were studied by regulating simulated body fluids with different pH values. The cytotoxicity, targeting effect, and drug release of human cervical cancer cell line (HeLa) were studied by cell vitality and imaging experiments. All the evidence suggests that the smart mesoporous CaCO3 nanoparticles may be a potential clinical application platform for cancer therapy.
研究领域:
生物材料学
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药剂学
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肿瘤学
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DOI
高影响因子
Scientific Reports
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2023
·Vol. 13
·期 1
·1-8
·
IF 4.6
Xin Jia-Xiang,Yang Guang,Zhang Huojun,Li Jianqi,Fu Caixia,Wang Jiachen,Tong Rui,Ren Yan,Wei Da-Xiu,Yao Ye-Feng
Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) have made great successes in clinical diagnosis, medical research, and neurological science. MRI provides high resolution anatomical images of tissues/organs, and MRS provides information of the functional molecules related to a specific tissue/organ. However, it is difficult for classic MRI/MRS to selectively image/probe a specific metabolite molecule other than the water or fat in tissues/organs. This greatly limits their applications on the study of the molecular mechanism(s) of metabolism and disease. Herein, we report a series of molecularly targeted MRI/MRS methods to target specific molecules. The optimal control method was used to efficiently prepare the singlet spin orders of varied multi-spin systems and in turn greatly expand the choice of the targeted molecules in the molecularly targeted MRI/MRS. Several molecules, such as N -acetyl- l -aspartic acid (NAA), dopamine (DA), and a tripeptide (alanine-glycine-glycine, AGG), have been used as targeted molecules for molecularly targeted MRI and MRS. We show in vivo NAA-targeted 1 H MRS spectrum of a human brain. The high-resolution signal of NAA suggests a promising way to study important issues in molecular biology at the molecular level, e.g., measuring the local pH value of tissue in vivo, demonstrating the high potential of such methods in medicine.
研究领域:
医学影像学
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分子生物学
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DOI
PubMed
高影响因子
Scientific Reports
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2012
·Vol. 2
·期 1
·1-8
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IF 0
Wang Bing,Yuan Huanxiang,Zhu Chunlei,Yang Qiong,Lv Fengting,Liu Libing,Wang Shu
For most molecule-targeted anticancer systems, intracellular protein targets are very difficult to be accessed by antibodies and also most efforts are made to inhibit protein activity temporarily rather than inactivate them permanently. In this work we firstly designed and synthesized multifunctional polymer-drug conjugates (polythiophene-tamoxifen) for intracellular molecule-targeted binding and inactivation of protein (estrogen receptor α, ERα) for growth inhibition of MCF-7 cancer cells. Small molecule drug was conjugated to polymer side chain for intracellular signal protein targeting and simultaneously the fluorescent characteristic of polymer for tracing the cellular uptake and localization of polythiophene-drug conjugates by cell imaging. Under light irradiation, the conjugated polymer can sensitize oxygen to produce reactive oxygen species (ROS) that specifically inactivate the targeted protein and thus inhibit the growth of tumor cells. The conjugates showed selective growth inhibition of ERα positive cancer cells, which exhibits low side effect for our intracellular molecule-targeted therapy system.
研究领域:
药理学
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肿瘤学
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生物化学
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DOI
PubMed
ACS Biomaterials Science & Engineering
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2022
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IF 5.395
Lingling Cai,Yanxing Wang,Xiangrong Peng,Wenjing Li,Ying Yuan,Xiaofeng Tao,Xinwei Yao,Ruichan Lv
Oral squamous cell carcinoma (OSCC) is the most common cancer in the oral and maxillofacial region. Due to the special physiological and anatomical position of the oral cavity, the disease often has a significant impact on the chewing, swallowing, language, and breathing functions of patients. In recent years, with the development of medical molecular biology, molecular targeted therapy has received increasing clinical attention and has gradually become a new method for the treatment of malignant tumors. In this research, gold nanostars with a high photothermal effect combined with the searched targeted antibody were used for OSCC therapy. We use the data set in the public database and construct a gene co-expression module by weighted gene co-expression network analysis (WGCNA). It was found that the turquoise module and the midnight blue module had the greatest connection to tumorigenesis. Cytoscape software was used to analyze the important modules, and the top 10 genes of each module were selected; the survival analysis of the top 10 genes was carried out by gene expression profiling interactive analysis (GEPIA), which indicated that these genes (SERPINH1, MMP11, ADAM12, FADS3, SLC36A2, C1QTNF7, SCRG1, and APOBEC2) have statistical significance as key genes that are related to the tumorigenesis of OSCC. Then, the anti-SERPINH1 antibody targeted to SERPINH1 was chosen as the inhibitor and combined with gold nanostars for photothermal assisted targeted therapy. Thus, the searched key genes can be regarded as biomarkers and therapeutic targets for further precise diagnosis.
研究领域:
肿瘤学
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分子生物学
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生物信息学
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诊疗学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2020
·Vol. 8
·期 35
·7931-7940
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IF 5.344
Man Zhang,Xuequan Zhang,Shengsheng Cai,Heng Mei,Yanmei He,Dennis Huang,Wenqiang Shi,Sai Li,Jun Cao,Bin He
Molecular targeted-photodynamic combinational therapy is a promising strategy to enhance antitumor effects; meanwhile, current nanocarriers face challenges of limited selective delivery and release of therapeutic agents to specific tumor sites, which significantly compromises their therapeutic efficacy. Herein, we report active-targeting, enzyme- and ROS-dual responsive nanoparticles (HPGBCA) consisting of CD44-targeting hyaluronic acid (HA) shells and afatinib (AFT)-loaded, ROS-sensitive poly(L-lysine)-conjugated chlorin e6 (Ce6) derivative nanoparticle cores (PGBCA). HPGBCA can actively carry AFT and Ce6 specifically to tumor cells due to the negatively charged HA and CD44-mediated active targeting. Subsequently, hyaluronidase in the endosome will further spur the degradation of the HA shell to prompt exposure of the positively charged PGBCA core for rapid endosomal escape and intracellular delivery of AFT and Ce6. Furthermore, the generation of ROS produced by Ce6 under NIR irradiation can trigger the rapid oxidation of the thioether linker to facilitate the release of AFT into the cytoplasm. In vitro and in vivo studies demonstrated that the released AFT and excessive ROS at the local site can synergistically induce cell apoptosis to enhance the therapeutic efficacy without side effects. Our developed intelligent nanoparticle provides new avenues to achieve on-demand, specific intracellular drug release for improved molecular targeted-photodynamic combination therapeutic efficacy.
研究领域:
癌症治疗
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纳米技术
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分子生物学
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药学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2021
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IF 5.811
Zhang Huaiyu,Zhang Jiayu,Liu Yilun,Jiang Yang,Li Zhongmin
Molecular targeted therapy has been proved effective in treatment of rectal cancer. Up-regulated expression of programmed death ligand-1 (PD-L1) was observed after the management of molecular targeted therapy, which made the therapeutic effect discounted. Tumors with higher PD-L1 expression were more sensitive and responsive to treatment of PD-L1 inhibitor. Therefore, the combination of molecular targeted therapy and immune checkpoint blockade makes sense. In this study, the copolymers of poly (ethylene glycol)-block-poly (L-leucine) (PEG-PLLeu) were synthesized as a thermosensitive hydrogel composite for consecutive release of regorafenib (REG) and BMS202. The mechanical properties of PEG-PLLeu were investigated, confirming that PEG-PLLeu (5 wt.%) was suitable for in situ injection as drug-delivery composite at low temperature and stable after sol-gel transition at body temperature. Importantly, the double drug loaded hydrogel showed superior antitumour activity over single drugs in an orthotopic rectal cancer model (CT26-Luc). Further analysis of the tumor tissues suggested that REG upregulated the expression of PD-L1 in tumor tissues. In addition, the immunosuppressive tumor microenvironment of CT26-Luc tumor was distinctly relieved under the effect of BMS202, as characterized by increased infiltration of CD8+ T cells in tumors and enhanced secretion of antitumour cytokines (IFN-γ and TNF-α). Moreover, the drug-loaded composite showed no obvious toxicity in histological analysis. Taken together, the administration of REG and BMS202 in the PEG-PLLeu composite could induce a synergistic effect in in situ treatment of rectal cancer without obvious toxicity, and thus represented a potential strategy for enhanced in situ therapeutic modality.
研究领域:
肿瘤学
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药学
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材料科学
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免疫学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2022
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IF 5.999
Jianbo Lin,Rujie Zheng,Liping Huang,Yuanrong Tu,Xu Li,Jianfeng Chen
Molecularly targeted drugs are flourishing in the clinical treatment of non-small cell lung cancer (NSCLC). However, the treatment of a single drug (such as Gefitinib (Geb)) had defects such as poor pharmacokinetics , insufficient drug delivery, and considerable toxic side effects, which greatly affect its therapeutic efficacy against NSCLC. To solve these issues, this study developed a new nanocomposite heterogeneous platform (MSNs@Ag@Geb-FA) that combined photothermal therapy and molecular targeted therapy. The high specific surface area empowered mesoporous silicon dioxide (SiO 2 ) heterostructure the ability to efficiently load Ag photothermal agents and anti-tumor drug Geb. Meanwhile, a favorable pH response (degradation of residual MnO 2 ) achieved the controlled release of Ag and Geb. Besides, the targeting and endocytosis properties of nano drugs were greatly improved through the modification of folic acid (FA). Both in vivo and in vitro experiments authenticated that this nanocomposite heterogeneous platform could effectively integrate the multiple tumor suppressor properties of Ag nanoparticles and cooperate with Geb to hasten A549 cell apoptosis, thereby achieving a favorable anti-tumor effect. This heterogeneous structure of the nanocomposite heterogeneous platform could provide an effective strategy for the treatment of NSCLC.
研究领域:
纳米技术
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药学
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癌症研究
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Mei Cong,Houjun Pang,Guangxing Xie,Feifei Li,Chunxiao Li,Hao Sun,Shaoyou Yang,Weidong Zhao
Purpose Molecular targeted therapy is one of the most pivotal strategies in the treatment of non-small cell lung cancer, yet its curative effect is severely compromised by the poor aqueous solubility, low bioavailability and inadequate tumor accumulation of targeted agents. To enhance the efficacy of targeted agents, we demonstrate a novel self-assemble amphiphilic molecule based on erlotinib as an effective nanodrug for anti-cancer treatment.Methods An amphiphilic molecule composed of hydrophobic erlotinib and hydrophilic biotin block was synthesized and characterized by nuclear magnetic resonance (NMR) as well as high-resolution mass spectrometry (HRMS). Then, nanoassemblies of the amphiphilic molecules are formulated by using nanoprecipitation method. Subsequently, the size, morphology, cell uptake, the anticancer activity and in vivo distribution of the newly constructed erlotinib nanodrug were systematically assessed by some methods, including transmission electron microscopy (TEM), dynamic light-scattering (DLS), flow cytometry, in vivo imaging system etc.Results We developed a novel nanoformulation of erlotinib, which possesses a high drug loading of 45%. With the features of well-defined structure and small size, the obtained nanodrug could be effectively accumulated in tumor sites and rapidly internalized by cancer cells. Finally, the erlotinib-based nanoformulation showed considerably better anticancer activity compared to free erlotinib both in vitro and in vivo. Moreover, the nanodrug displayed great tolerability.Conclusion Combining the advantageous features of both nanotechnology and self-assemble, this novel erlotinib nanomedicine constitutes a promising therapeutic candidate for cancer treatment. This study also underlines the potential use of amphiphilic molecule for improving drug efficacy as well as reducing drug toxicity, which could become a general strategy for the preparation of nanodrugs of active agents.
研究领域:
药学
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癌症研究
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纳米技术
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药物递送系统
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DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2024
·Vol. 22
·期 1
·1-21
·
IF 10.6
Chen Shang,He Yan,Huang Xin,Shen Yao,Zou Qingshuang,Yang Gun,Fu Li,Liu Quan,Luo Dixian
Tumor-associated macrophages (TAMs) are a promising target for cancer immunotherapy, but delivering therapeutic agents to TAMs within the tumor microenvironment (TME) is challenging. In this study, a photosensitive, dual-targeting nanoparticle system (M.RGD@Cr-CTS-siYTHDF1 NPs) was developed. The structure includes a shell of DSPE-modified RGD peptides targeting integrin receptors on tumor cells and carboxymethyl mannose targeting CD206 receptors on macrophages, with a core of chitosan adsorbing m6A reading protein YTHDF1 siRNA and chromium nanoparticles (Cr NPs). The approach is specifically designed to target TAM and cancer cells, utilizing the photothermal effect of Cr NPs to disrupt the TME and deliver siYTHDF1 to TAM. In experiments with tumor-bearing mice, M.RGD@Cr-CTS-siYTHDF1 NPs, when exposed to laser irradiation, effectively killed tumor cells, disrupted the TME, delivered siYTHDF1 to TAMs, silenced the YTHDF1 gene, and shifted the STAT3-STAT1 equilibrium by reducing STAT3 and enhancing STAT1 expression. This reprogramming of TAMs towards an anti-tumor phenotype led to a pro-immunogenic TME state. The strategy also suppressed immunosuppressive IL-10 production, increased expression of immunostimulatory factors (IL-12 and IFN-γ), boosted CD8 + T cell infiltration and M1-type TAMs, and reduced Tregs and M2-type TAMs within the TME. In conclusion, the dual-targeting M.RGD@Cr-CTS-siYTHDF1 NPs, integrating dual-targeting capabilities with photothermal therapy (PTT) and RNA interference, offer a promising approach for molecular targeted cancer immunotherapy with potential for clinical application. Graphical Abstract
研究领域:
癌症生物学
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纳米技术
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免疫疗法
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分子生物学
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药理学
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DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2025
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IF 4.9
Hua Nie,Xiao-Min Liu,Sheng-Yuan Zhang,Qi-Xuan Yang,Huang Zeng,Xiao-Dong Luo,Jiun-Long Yang
This study optimized polyethylene glycol (PEG) chain length in cholesterol-GalNAc conjugates (CHS-PEG n -6-GalNAc, n = 2–5) to enhance hepatic targeting of liposomes by balancing glycan exposure and glycocluster conformation. The conjugates were synthesized via enzymatic catalysis and incorporated into liposomes (LP-PEG n -6-GalNAc). Systems were evaluated through in vitro HepG2 cell uptake, in vivo murine biodistribution, and molecular dynamics (MD) simulations. LP-PEG n -6-GalNAc showed significantly higher in vitro uptake ( P < 0.01 vs unmodified liposomes) and superior in vivo hepatic accumulation ( P < 0.01). ASGPR-mediated targeting was confirmed by competitive inhibition (GalNAc in vitro , asialofetuin in vivo ; both P < 0.01). Targeting efficiency exhibited identical PEG-length dependency: PEG 3 > PEG 4 > PEG 5 > PEG 2 . MD simulations revealed a dual mechanism: Shorter chains (PEG 2 ) maintained higher glycocluster stability (frequency = 40.8 %; RMSF = 0.39 Å) but limited GalNAc accessibility (SASA = 49.9 %). Longer chains (PEG 4-5 ) increased SASA (73.38–86.08 %) but reduced stability (frequency = 23.0–35.0 %; RMSF = 1.05–1.30 Å). PEG 3 balanced SASA (61.7 %) and stability (36.2 %), synergistically enhancing uptake. This provides the first evidence that PEG length coordinates glycan accessibility and glycocluster stability to improve hepatic targeting.
研究领域:
药物递送
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纳米医学
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分子靶向
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糖化学
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药学
✓ 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）