INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2021
·
IF 5.875
Yue Yang,Kaiqing Yun,Yunjian Li,Ling Zhang,Wenxuan Zhao,Zhihong Zhu,Baocheng Tian,Fen Chen,Weisan Pan
Integration of multiple therapies into one nanoplatform holds great promise to overcome the shortcomings of traditional single-modal therapy and achieve favorable antitumor efficacy. Herein, we constructed a dual receptor-targeting nanomicelle system with GSH-responsive drug release for precise fluorescence imaging and superior chemo-phototherapy of cancer. The synthetic amphiphilic hyaluronic acid derivative (FHSV) could self-assemble into nanomicelles in aqueous media. Then, paclitaxel (PTX) and photosensitizer IR780 iodide (IR780) were co-loaded into the micelles by a simple dialysis method. The resulting IR780/PTX/FHSV micelles with a particle size of 150.2 ± 6.9 nm exhibited excellent stability, GSH-responsive drug release and good photothermal/photodynamic efficacy. Once accumulated at the tumor sites, IR780/PTX/FHSV micelles efficiently entered tumor cells through receptor-mediated endocytosis and then rapidly release PTX and IR780 under GSH-rich tumor microenvironment . Upon NIR laser irradiation, IR780 produced local hyperthermia and sufficient reactive oxygen species to promote tumor cells apoptosis and necrosis. The results of in vitro and in vivo experiments consistently demonstrated that compared with single chemotherapy and phototherapy, the chemo-phototherapy could more efficiently kill tumor cells by synergistic antitumor effect. Therefore, our study provides a novel and efficient approach for multimodal treatment of malignant tumor.
研究领域:
药剂学
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肿瘤学
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生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2024
·
IF 2.7
Yaqi Xiao,Zhi Cai,Ying Yi,Yihua Yin,Weiquan Cai,Guanghua He,Jingli Zhang,Wenjin Xu,Yaru Li
Cationic photosensitizers have higher photodynamic antibacterial activity compared with anionic photosensitizers, and with low toxicity and no drug resistance. However, their poor photostability and low utilization rate limit their practical applications. Herein, a new strategy for the construction of a GSH-responsive antibacterial nanogel system is developed via the electrostatic interaction between methylene blue (MB) and sulfonated sodium alginate (HSSA) to self-assemble into nanoparticles followed by sulfhydryl cross-linking in an aqueous solution. The photobleaching of MB can be inhibited due to the self-aggregation-caused quenching (ACQ) effect, but the photodynamic activity can be restored by breaking the disulfide-crosslinking bonds in the nanogel in response to 10 mM GSH. In vitro antibacterial tests prove that the system has antibacterial activity beyond anionic photosensitizers. Antibacterial studies on plants show that the system has targeted antibacterial activity on infected plants and good wettability, retention, and adhesion to plant leaves. Safety evaluation shows that the system has no obvious toxic effect on plants. Therefore, this study provides a new approach to the discovery of novel photodynamic bactericides.
研究领域:
生物材料学
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微生物学
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植物病理学
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产品关联
DOI
高影响因子
EUROPEAN POLYMER JOURNAL
·
2022
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IF 5.546
Jinsheng Liu,Zhuoer Dai,Pingkai Shen,Yihua Yin,Yin Yi,Weiquan Cai,Lihong Fan,Guanghua He,Jingli Zhang,Wenjin Xu,Silin Chen,Jiayi Pan
To enhance bacteria-targeting and improve bactericidal activity, a novel GSH-responsive photodynamic antimicrobial nanosystem based on Alginate oligosaccharide-protoporphyrin IX (AOS-ss-PpIX) conjugates were constructed. The fluorescence self-quenching caused by the aggregation of PpIX groups into hydrophobic core could promote the photostability of PpIX and avoid the phototoxicity of the non-infected sites of the target plants. But once exposed to GSH stimulus, the recovery of high photodynamic activity were observed due to the destruction of the system and accompanied by the release of thiolated PpIX, and the photodynamic activity after 2 h was higher than that of PpIX under the same conditions. Furthermore the system showed more efficient photodynamic antibacterial capacity under light exposure. Moreover, the pot experiment also verified that the system showed outstanding control efficacy against cabbage soft rot caused by Erwinia carotovora Sclerotinia. Safety test exhibited that the size of nanoparticles can restrict the entry of nanoparticles into the plant cells to trigger photocytotoxicity. The design strategy provides a platform for promoting the utilization of photoactivated pesticides and reducing or avoiding their harm to target plants and the environment.
研究领域:
植物学
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微生物学
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农药科学
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产品关联
DOI
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 19
·6972
·
IF 4.6
Zheng Huang,Tong Xian,Xiangyi Meng,Huaisong Hu,Lixia Gao,Jiuhong Huang,Donglin Yang,Kepeng Ou,Bochu Wang,Yimei Zhang
Photodynamic therapy (PDT) is an effective noninvasive therapeutic strategy that has been widely used for anti-tumor therapy by the generation of excessive highly cytotoxic ROS. However, the poor water solubility of the photosensitizer, reactive oxygen species (ROS) depleting by high concentrations of glutathione (GSH) in the tumor microenvironment and the activation of DNA repair pathways to combat the oxidative damage, will significantly limit the therapeutic effect of PDT. Herein, we developed a photosensitizer prodrug (CSP) by conjugating the photosensitizer pyropheophorbide a (PPa) and the DNA-damaging agent Chlorambucil (Cb) with a GSH-responsive disulfide linkage and demonstrated a multifunctional co-delivery nanoplatform (CSP/Olananoparticles (NPs)) together with DSPE-PEG2000and PARP inhibitor Olaparib (Ola). TheCSP/Ola NPsfeatures excellent physiological stability, efficient loading capacity, much better cellular uptake behavior and photodynamic performance. Specifically, the nanoplatform could induce elevated intracellular ROS levels upon the in situ generation of ROS during PDT, and decrease ROS consumption by reducing intracellular GSH level. Moreover, theCSP/Ola NPscould amplify DNA damage by released Cb and inhibit the activation of Poly(ADP-ribose) polymerase (PARP), promote the upregulation of γ-H2AX, thereby blocking the DNA repair pathway to sensitize tumor cells for PDT. In vitro investigations revealed thatCSP/Ola NPsshowed excellent phototoxicity and the IC50values ofCSP/Ola NPsagainst MDA-MB-231 breast cancer cells were as low as 0.05–01 μM after PDT. As a consequence, the co-delivery nanoplatform greatly promotes the tumor cell apoptosis and shows a high antitumor performance with combinational chemotherapy and PDT. Overall, this work provides a potential alternative to improve the therapeutic efficiency of triple negative breast cancer cell (TNBC) treatment by synergistically enhancing DNA damage and disrupting DNA damage repair.Keywords:chemo-photodynamic therapy;DNA damage repair;PARP inhibitor;co-delivery;GSH-responsive
研究领域:
癌症治疗
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药学
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纳米技术
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
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2021
·
IF 0
Hui-Zhen Yang,Ji Zhang,Yu Guo,Lin Pu,Xiao-Qi Yu
Nonviral gene vectors with stimulus responsiveness and self-reporting properties have broad application prospects in gene therapy. Herein, we developed a nanosized reduction-responsive cationic liposomal vector formed from DNS(Zn), in which a naphthalimide–sulfonamide group was used as the glutathione (GSH)-responsive group to generate a blue fluorescence signal at 458 nm. Macrocyclic polyamine (cyclen) was used as a cationic headgroup to facilitate Zn(II) coordination, which may reduce the cytotoxicity and improve transfection efficiency. The Zn-free and nonresponsive analogues were used for comparison. Fluorescent assays revealed that the GSH response of DNS(Zn) could increase the blue fluorescence signal and improve the DNA release in cells. The title material also showed higher positive ζ-potential than its nonresponsive analogue, resulting in stronger DNA binding ability and better cellular uptake. These advantages made DNS(Zn) a good candidate for nonviral gene delivery, and the transfection efficiency in HeLa cells was distinctly higher than that of its analogue and the commercially available transfection reagent. Besides plasmid DNA, DNS(Zn) could also deliver small interfering RNA (siRNA) with good gene silencing efficiency, extending the application of the liposomes. These results suggest that DNS(Zn) can serve as a highly efficient nucleic acid delivery vector with reduction-responsive fluorescence self-reporting ability in tumor cells.
研究领域:
生物化学
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分子生物学
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基因治疗
✓ 已验证
产品关联
DOI
PubMed
BIOMACROMOLECULES
·
2023
·
IF 6.2
Yingping Zeng,Guangtao Song,Shufen Zhang,Sufen Li,Tingting Meng,Hong Yuan,Fuqiang Hu
The tumor microenvironment (TME) of breast cancer is hypoxic, which can promote tumor progression, including invasion and metastasis, and limit the efficacy of anti-tumor treatment. Nitric oxide (NO) can dilate blood vessels, effectively alleviate hypoxia, and regulate the TME, which has the potential to improve the anti-tumor therapeutic efficacy. Here, chitosan (CO) and octadecylamine (ODA) were linked by the disulfide bond, and the LinTT1 peptide was linked onto CO–SS–ODA for targeting tumor cells and endothelial cells in tumors. The NO donor S-nitroso-N-acetylpenicillamine (SNAP) was connected to CO. Doxorubicin (DOX) was encapsulated, and GSH hierarchically responsive polymer micelles (TSCO–SS–ODA/DOX) were constructed for the treatment of breast cancer. The micelles had differently responsive drug release in different GSH concentrations. In endothelial cells, the micelles rapidly responded to release NO. In tumor cells, the disulfide bond rapidly broke and released DOX to effectively kill tumor cells. The disulfide bond was not sensitive to GSH concentration in endothelial cells, which had less release of DOX. The killing effect of the micelles to endothelial cells was much lower than that to tumor cells. The cell selective drug release of the drug delivery systems enabled safe and effective treatment of drugs. TSCO–SS–ODA/DOX, which had the excellent ability to target tumors, can alleviate tumor hypoxia, decrease the infiltration of M2 macrophages in tumors, increase the infiltration of M1 macrophages in tumors, and remodel the TME. Notably, TSCO–SS–ODA/DOX can significantly inhibit the growth of the primary tumor and effectively inhibit tumor metastasis. The drug delivery system provided a potential solution for effectively treating breast cancer.
研究领域:
药学
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肿瘤学
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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
Journal of Pharmaceutical Analysis
·
2025
·
IF 8.9
Chenqian Feng,Lingfeng Zhou,Bo Chen,Hui Li,Min Mu,Rangrang Fan,Haifeng Chen,Gang Guo
Melanoma, a common malignant skin tumor, faces challenges with multidrug resistance and high recurrence rates. Combining photodynamic therapy (PDT) and immunotherapy offers a promising personalized treatment approach. However, poor water solubility and significant side effects of photosensitizers and immune checkpoint inhibitors (ICIs) limit their application. Enhancing delivery efficiency while reducing adverse effects is crucial. Herein, we formulate BM@HSSC nanoparticles (NPs), which consist of a reduction-responsive hyaluronic acid (HA) backbone modified with photosensitizer Chlorin e6 (Ce6) and loaded with the programmed cell death-ligand 1 (PD-L1) inhibitor BMS-1. This system synergistically integrates PDT, immunogenic cell death (ICD), and immunotherapy for melanoma treatment. BM@HSSC NPs target and accumulate at the tumor site via the CD44 receptor. The disulfide bonds in the nanoparticles react with high GSH concentrations in tumor cells, rapidly releasing Ce6 and BMS-1. Under 660 nm laser irradiation, BM@HSSC NPs generate cytotoxic reactive oxygen species (ROS), inducing cell apoptosis and triggering ICD via. PDT Damage-associated molecular patterns (DAMPs) and tumor-associated antigens (TAAs) released from ICD promote dendritic cell (DC) maturation, enhancing antigen presentation and activating cytotoxic T lymphocytes (CTLs). Meanwhile, BMS-1 blocks the programmed cell death-1 (PD-1)/PD-L1 pathway, countering the immunosuppressive tumor microenvironment and inhibiting tumor cell immune escape. This strategy amplifies antitumor immune responses by enhancing immunogenicity and synergizing with ICIs, resulting in robust antitumor efficacy.
研究领域:
肿瘤学
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纳米医学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Chunxi Qian,Bandar Al-Hamyari,Xiaofei Tang,Bo Hou,Shuaibo Yang,Guifang Zhang,Huijuan Lv,Zhigang Yang,Zhaohui Wang,Yanbin Shi
Having benefited from the combination of different therapeutic modalities, functionalized nanoplatforms with synergistic strategies have aroused great interest in anticancer treatment. Herein, an engineered, a biodegradable hollow mesoporous organosilica nanoparticle (HMON)-based nanoplatform was fabricated for photothermal-enhanced chemotherapy of tumor. For the first time, we demonstrated that HMONs could serve as nanocarriers for co-delivering of both the paclitaxel and photothermal agent new indocyanine green (IR820), denoted as Paclitaxel/IR820@ HMONs-PEG. The as-prepared nanosystem exhibited a high paclitaxel-loading capacity of 28.4%, much higher than most paclitaxel-loaded nanoformulations. Furthermore, incorporating thioether bonds (S-S) into the HMONs’ framework endowed them with GSH-responsive biodegradation behavior, leading to the controllable release of drugs under a tumor reducing microenvironment, and hindered the premature release of paclitaxel. Upon being irradiated with an NIR laser, the obtained co-delivery nanosystem exhibited great photothermal properties generated from IR820. The fabricated nanocomposites could significantly suppress tumor growth under NIR laser irradiation, as validated by in vitro and in vivo assessments. Combined with outstanding biocompatibility, the constructed nanosystem holds great potential in combinational antitumor therapy.
研究领域:
纳米技术
·
癌症治疗
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材料科学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Wenjia Wang,Xiaoqin Zhang,Zhiqian Li,Dayi Pan,Hongyan Zhu,Zhongwei Gu,Jie Chen,Hu Zhang,Qiyong Gong,Kui Luo
To achieve target delivery of anti-tumor drugs with great biocompatibility into tumor tissues, a stimuli-responsive dendronized hyaluronic acid (HA)-docetaxel conjugate (HA-DTX-Dendron, HADD) was designed and prepared. The incorporation of HA in HADD improved the delivery of DTX to tumor cells with rich CD44 receptors. Enhanced biocompatibility and therapeutic outcomes were achieved using glyodendrons-modified HA and tumor microenvironment-responsive linkers in HADD. The glycodendron was connected with HA via GSH-responsive disulfide bonds , and the drug DTX was linked to the carrier via a cathepsin B-responsive tetrapeptide GFLG. This design resulted in self-assembly nanostructures for facilitating uptake of HADD by tumor cells and rapid release of DTX to exert its therapeutic effect. Compared to free DTX, HADD showed much higher tumor growth inhibition in the MDA-MB-231 tumor-bearing mice model (up to 99.71%), and no toxicity was observed. Therefore, HADD could be employed as an efficacious nano-agent for treating triple negative breast cancer (TNBC).
研究领域:
药学
·
癌症研究
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2020
·Vol. 137
·期 43
·49339
·
IF 2.52
He-Yi Li,Fang-kun Jing,Jun-Feng Hao
In order to reduce the toxic side effects of chemotherapeutic drugs and improve the targeting and efficiency of cancer treatment, the development of drug delivery system has received great attention. In this study, second generation polyglutamic acid dendrimers (G 2 ) are used as basic materials to produce porous nanoparticles through cross link by crosslinkers containing disulfide bonds. The crosslinked products (G 2 ) n have negative electricity and abundant voids, which enable them to adsorb the electronegative anticancer drug DOX. At the same time, in order to transport DOX to the tumor site, we modified FA on DOX and encapsulated it in magnetic mesoporous silica (FA-DOX-MSNs). Therefore, the final nanoparticles (FA-DOX-MSNs/(G 2 ) n ) not only have dual targeting ability to transport DOX to the tumor site, but also have reductive responsiveness that can release drugs responsively in the tumor cells. In addition, it has good biocompatibility and endocytosis ability.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
CERAMICS INTERNATIONAL
·
2020
·
IF 3.83
Jinyue Zhang,Mingshi Jin,Yong Il Park,Longyi Jin,Bo Quan
Manganese silicate nanoparticles have recently attracted great attention due to the effectiveness of T 1 -weighted magnetic resonance imaging (MRI) contrast agents (CAs) in the mildly acidic and high glutathione (GSH) conditions of the tumor microenvironment. Herein, ultra-small hollow manganese silicate (UHMS) nanoparticles were prepared via a facile, economical, and eco-friendly method based on a hydrothermal process using small silica nanoparticles as both the silicon source and templates. The nanoparticles showed remarkable biocompatibility and dispersion stability after modification with polyethylene glycol (PEG). Owing to their ultra-high longitudinal relaxation rate (r 1 ) at low pH values and high GSH levels, the [email protected] nanoparticles have performed an excellent pH/GSH-responsive T 1 -weighted MRI. Meanwhile, the nanoparticles showed insignificant cytotoxicity in vitro and in vivo. Therefore, the [email protected] nanoparticles show promise as T 1 -MRI CAs in the tumor microenvironment and may be used to assist in clinical cancer diagnosis.
研究领域:
纳米技术
·
材料科学
·
医学成像
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2024
·
IF 4.9
Zhiyuan Liu,Rui Sun,Yaxuan Huang,Fengyun Xu,Nan Li,Wei Zhang,Pengfei Ge,Wenke Zhang
Shikonin (SHK), an active naphthoquinone pigment isolated from the root of Chinese herbal medicine has been proven to have a significant therapeutic effect on breast cancer. However, the poor water solubility as well as the lack of tumor targeting restrict the practice application of SHK molecules as chemotherapeutic agents. Here, SHK drugs were chemically conjugated to polyethylene glycol (PEG) molecules via a disulfide bond (referred to as SHK-SS-PEG) through a facile one-step strategy. The conjugates exhibited an excellent water solubility of 12.96 mM, which is ca. 7807 times as high as that of pure SHK drugs. Noteworthily, the conjugates can self-assemble into spherical micelles with an average particle size of 106 nm, facilitating in vivo delivery as well as the accumulation in tumor tissues based on the enhanced permeability and retention (EPR) effect. Moreover, the disulfide bond enables rapid cleavage of micelles and efficient release of SHK molecules from the conjugates in response to reduced Glutathione (GSH) overexpressed within tumor cells. Thanks to the GSH-responsiveness release of SHK, the conjugate-based micelles (containing 6 μM SHK) resulted in the cell killing rate of 73 % for the MCF-7 breast cancer cells after 48 h incubation, which is 45 % higher than that for the HUVEC normal cells. All these collective beneficial properties make the SHK-SS-PEG conjugate a promising candidate for the treatment of many types of cancers.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 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）