Biomaterials Advances
·
2023
·
IF 0
Yiqing Liu,Peiyong Guo,Xinhao Dong,Yina Xu,Dan Li,Hua Zheng,Jianhong Liao
Here, we combined reversible addition-fragmentation chain transfer (RAFT) polymerization and amide coupling reaction to develop a novel drug-polymer conjugate using poly(AMA- co -IMMA)-b-poly(OEGMA) (termed as PAIPO) as nanocarriers. In order to enhance cellular uptake and obtain subsequent endo/lysosomal escape capacity, the dual-drugs-conjugated prodrug was then coupled with 2,3-dimethylmaleimide (DA) moieties and implanted with imidazolyl groups, respectively. Paclitaxel (PTX) was conjugated to PAIPO via 3,3′-dithiodipropionic acid (DPA) to construct a GSH-responsive moiety, while doxorubicin (DOX) was conjugated to PAIPO via 4-formyl benzoic acid to construct a pH-responsive moiety, which synergistically enabled a synchronized and precise drug delivery. The micelles self-assembled from DOX/ [email protected] DA showed an ideal average diameter (163.2–178.3 nm), contributing to passive targeting by the EPR effect. Moreover, a switch of the surface Zeta potential of micelles from steady negatively charged (− 9.74 ± 0.54 mV) at pH 7.4 to positively charged (+ 6.33 ± 1.25 mV) at pH 6.5, facilitated the long blood circulation and cellular endocytosis of micelles, respectively. More importantly, in vitro studies confirmed that DA M(DOX n /PTX) exhibited a strong synergism against tumor cells, and under slightly acidic conditions (pH 6.5), the combination index (CI) values for DA M(DOX 1 /PTX) on HeLa and Skov-3 cells were estimated to be 0.47 and 0.49 (previous to be 0.50 and 0.56 at pH 7.4), respectively. And in vivo results showed effective tumor accumulation potential, remarkable biosafety, and biocompatibility. Combined, such synchronized delivery approach based on multi-responsive micelles might potentiate the efficacy of combination chemotherapy in clinical cancer treatment.
研究领域:
药物递送系统
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肿瘤学
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生物材料
✓ 已验证
产品关联
DOI
PubMed
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
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Qianyu Yang,Gang Wu,Yefeng Yang,Yang Zhou,Jiali Song,Huile Gao,Weiyuan Huang
Based on the properties of photodynamic therapy (PDT) and magnetic resonance imaging (MRI), combining them to construct multifunctional nanotheranostics can leverage strengths and avoid weaknesses for tumor diagnosis and treatment. However, certain problems remain unsolved, notably the short observation window caused by insufficient retention time. In this study, a GSH-responsive shape-transformable nanotheranostics Gd-Ce6-FFVLGGGC-SS-PEG are designed (abbreviated as GdCFS) by combining a single metal Gd with Ce6, and peptide (Phe-Phe-Val-Leu-Gly-Gly-Gly-Cys) disulfide-conjugated with polyethylene glycol (PEG) to perform dual-modal T 1 /T 2 MRI specifically at the tumor site. Due to its amphiphilic features, GdCFS can self-assemble to spherical nanoparticles, while transforming to nanofibers (NFs) in the presence of intracellular overexpressed GSH stimuli. After NFs formation, the hydrophobic core of GdCFS is exposed, resulting in T 1 positive contrast enhancement, whereas NFs can simultaneously achieve T 2 negative contrast enhancement. Furthermore, GSH depletion can cause imbalance in intracellular redox state, ultimately improving PDT efficacy. GdCFS benefits from the shape-transformation in terms of sufficient retention time, thus positively minimizing the toxicity risk. On the tumor model of nasopharyngeal carcinoma, in vivo and in vitro outcomes confirm that GdCFS can be a promising candidate for early diagnosis, real-time monitoring, and precise treatment of tumors with great biocompatibility.
研究领域:
医学
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纳米医学
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肿瘤学
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影像学
✓ 已验证
产品关联
DOI
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
✓ 已验证
产品关联
DOI
高影响因子
POLYMER DEGRADATION AND STABILITY
·
2019
·
IF 3.78
Jianbing Li,Xiufang Li,Hui Liu,Tao Ren,Ling Huang,Zhiwei Deng,Yanjing Yang,Shian Zhong
Glutathione (GSH)/light dual-responsive supramolecular drug carriers (abbreviated as CPAP) based on CD-PEG⊃Azo-PCL were fabricated for intracellular delivery of doxorubicin (DOX). The carriers were spherical with a diameter of 70–90 nm and exhibited GSH/light sensitivity. The GSH response attributed to disulfide bonds between PEG and β-cyclodextrin (β-CD), and the light response was achieved by a simple host-guest interaction between β-CD and azobenzene . DOX was encapsulated into the hydrophobic core of CPAP. The drug loaded CPAP ( [email protected] ) displayed the fastest drug release in the presence of GSH and light simultaneously. The cytotoxicities of CPAP and [email protected] were explored by SKOV3 cells and HEK293T cells. The results of cell experiments indicated that [email protected] could effectively inhibit cancer cells while had reduced toxicity to normal cells. We believe that [email protected] drug delivery system may present promising application for precisely controllable drug release.
研究领域:
生物材料学
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药剂学
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肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
EUROPEAN POLYMER JOURNAL
·
2022
·
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
✓ 已验证
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
POWDER TECHNOLOGY
·
2025
·
IF 4.6
Menglu An,Weiying Wang,Jingguo Li,Shaokui Cao,Yingliang Liu,Jun Shi
MnO 2 nanosheets have attracted extensive attention in the field of photothermal therapy due to their excellent pH/glutathione (GSH) responsiveness. In this study, MoS 2 @gold nanorods (AuNRs)/polydopamine (PDA)@MnO 2 (400–500 nm) nanocomposites with controllable drug release property were prepared by covering MnO 2 nanosheets around near-infrared (NIR) responsive MoS 2 @AuNRs (100–200 nm) via in-situ redox reaction. The large surface area and strong negative charge of MnO 2 nanosheets ensured that MoS 2 @AuNRs/PDA@MnO 2 had a high loading efficiency of 92.44 % for doxorubicin hydrochloride (DOX). MoS 2 @AuNRs/PDA@MnO 2 revealed significant NIR/pH/GSH triple-responsive drug release properties owing to the synergistically enhanced NIR photothermal-response of MoS 2 @AuNRs (61.10 % of photothermal conversion efficiency) and the reaction between MnO 2 and GSH in weakly acidic media. In addition, in vitro cell viability results confirmed that MoS 2 @AuNRs/PDA@MnO 2 could efficiently kill tumor cells under the dual action of acidic media and NIR laser. This study develops a novel nanocarrier with NIR/pH/GSH triple-responsive drug delivery capability, which has broad applications in photothermal therapy and intelligent drug delivery.
研究领域:
生物医学工程
·
纳米医学
·
肿瘤治疗
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Polymeric Materials and Polymeric Biomaterials
·
2022
·
IF 3.221
Hengquan Zhou,Guiying Li,Lei Guo,Qian Tao,Songmei Ma,Xunyong Liu
pH and GSH dual-responsive nanoparticles with fluorescence detection were successfully prepared from the polydopamine coating on the surface of mesoporous silica via disulfide bonds (MSN-SS-PDA). The average diameter of nanoparticles was about 80–100 nm with a well-ordered mesoporous structure. The outer layer of PDA was about 10.0 nm acting as a pH and GSH sensitive gatekeeper to control drug release. Doxorubicin (DOX) was loaded into mesoporous channels to evaluate the drug loading capacity and controlled release performance. TPE-4OH, an aggregation-induced emission (AIE) luminescence, was adhered to the surface of PDA for detection of drug release in real-time. The drug release from MSN-SS-PDA nanoparticles was enhanced under acidic solutions or high GSH concentrations. The fluorescence intensity decreased gradually with the drug release, which can be used for monitoring of release process. Besides, the nanoparticles exhibited good photothermal conversion capability due to the PDA layer under near-infrared light irradiation at 808 nm. These nanoparticles present a promising future for combination therapy and real-time tracking of the release process.
研究领域:
材料科学
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Bio Materials
·
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
·
分子生物学
·
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
·
生物医学工程
✓ 已验证
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
·
纳米医学
·
免疫学
✓ 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）