Nanoscale Advances
·
2025
·
IF 4.6
Mengting Tong,Guangpeng Chen,Yong Dong,Yubin Pan,Yanan Xue,Da Li
Despite the progress made in novel immunotherapy for hepatocellular carcinoma (HCC), drug resistance remains a challenging problem. In this study, we developed a stepwise nanodrug delivery system, known as Au-SS-PEG/Sor/ATP aptamer /LHRH-MPG ΔNLS , to adapt to the high concentrations of glutathione (GSH) and adenine nucleoside triphosphate/adenosines (ATP/ADO) found in cancer cells and the tumor microenvironment (TME). This system utilizes novel Au nanoclusters conjugated with disulfide-linked PEG as vectors to transport sorafenib (Sor) and an ATP-binding nucleic acid aptamer (ATP apt ). It can enter HCC cells through luteinizing hormone-releasing hormone (LHRH)-MPG ΔNLS (LM). Within the cells, the disulfide bonds of the nanoclusters are cleaved by the high levels of GSH, leading to the release of Sor/ATPapt. This release can be further triggered by ATP/ADO, resulting in a stepwise drug release mechanism. Furthermore, this nanodrug system has exhibited the ability to overcome αPD-1 resistance in HCC tumors. In summary, our novel drug delivery system demonstrates a dramatic anti-HCC effect and holds great potential for treating HCC patients. Synthesis and mechanistic illustration of Au-SS-PEG/Sor/ATP apt /LM nanoclusters for the treatment of hepatocellular carcinoma (HCC).
研究领域:
肿瘤学
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纳米医学
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免疫治疗
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药物递送
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2023
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IF 5
Yanan Bu,Hongcai Wang,Ting Wu,Xiuqiong Chen,Siyuan Zhao,Huiqiong Yan,Qiang Lin
Nowadays, self-assembled polymeric micelles from amphiphilic polymer conjugates are urgently needed to enhance drug targeting and release efficiency. On account of the excellent properties of alginate and the redox-responsiveness of disulfide bonds , a redox-sensitive alginate–SS–ibuprofen derivative (LSA–SS–IBU) based anti-tumor target drug delivery system was created by attaching the hydrophobic ibuprofen (IBU) onto the hydrophilic alginate molecular skeleton through disulfide linkages for glutathione (GSH) triggered delivery of doxorubicin hydrochloride (DOX). The structure and self-assembly behavior of the synthesized LSA–SS–IBU was systematically evaluated by FT-IR spectrometer, 1 H NMR spectrometer, fluorescence spectrophotometer (FM), transmission electron microscope (TEM) and dynamic light scattering (DLS). Furthermore, the in vitro release of drugs from the LSA–SS–IBU micelles loaded with DOX was examined, along with the assessment of their cytotoxicity to HeLa cells. The resultant LSA–SS–IBU had a critical micelle concentration (CMC) value of 0.19 mg/mL that was able to self-assemble into the spherical micelles with the particle size and zeta potential of 148.2 ± 4.3 nm (PDI = 0.25) and −47.2 ± 0.4 mV, respectively. At a mass ratio of 3:10 for DOX/LSA–SS–IBU, the LSA–SS–IBU micelles achieved drug loading ratio (DLR) and encapsulation efficiency (EE) values of 12.2 % and 46.3 %, respectively. Furthermore, the in vitro drug release study indicated that the total drug release percentage of the drug-encapsulated LSA–SS–IBU micelles in PBS with the presence of 10 mmol/L GSH for 12 h exceeded 67.0 %, demonstrating a substantial increase compared to that in GSH-free PBS. The in vitro cytotoxicity findings indicated that LSA–SS–IBU had good biocompatibility , while the IC 50 value and the cell viability of DOX-loaded LSA–SS–IBU micelles cultured with HeLa cells for 48 h was 2.2 μg/mL and less than 20.1 %, respectively, which could significantly inhibit the growth of HeLa cells. Therefore, redox-responsive LSA–SS–IBU micelles had potential applications in cancer therapy for hydrophobic anti-tumor drug delivery.
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DOI
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
·
IF 2.5
Siyu Xia,Lin Wu,Jing Chen,Kuanyu Li,Dezhi Bian
Diabetes is one of the most prevalent metabolic disorders, and its incidence has been experiencing a steady annual rise in recent years. Diabetic peripheral neuropathy (DPN) represents the most frequent adverse complication, exerting a profound impact on the quality of life for those suffering from diabetes. The etiology of DPN is complex, including impaired mitochondrial function. Iron-sulfur clusters (Fe–S) are essential cofactors for numerous essential enzymes crucial for mitochondrial function. Our previous study showed that expression of Frataxin, encoded by the Fxn gene, is downregulated in leptin receptor knockout (so-called db/db) mice, a commonly used DPN mouse model. Fxn is one of the core components of Fe–S biogenesis machinery. Here, we found that the mitochondria-targeted antioxidant SS-31 markedly improved the behavioral indices and significantly mitigated the damage to the sciatic nerve. SS-31 treatment effectively elevated Fxn expression, meliorated mitochondrial function, and inflammation in the sciatic nerve (SCN). We also found that SS-31 effectively mitigated high glucose-induced disruption of iron and redox homeostasis in RSC96 cells, a typical cell model of DPN, thereby improving mitochondrial function. These findings suggest enhancing Fe–S biogenesis could be an effective therapeutic strategy for treating DPN.
研究领域:
代谢性疾病
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神经科学
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分子生物学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
·
IF 10.7
Wei Sun,Zi-Xi Wang,Yuxin Guo,Chengcheng Li,Ge Gao,Fu-Gen Wu
Iodine (I 2 ) as a broad-spectrum antiseptic has been widely used for treating bacterial infections. However, I 2 has low water-solubility and sublimes under ambient conditions, which limits its practical antibacterial applications. The highly specific and sensitive reaction between I 2 and starch discovered 200 years ago has been extensively applied in analytical chemistry, but the antibacterial activity of the I 2 − starch complex is rarely investigated. Herein, we develop a novel type of iodine-based antiseptics, iodine−soluble starch (I 2 -SS) cryogel, which can dissolve in water instantly and almost completely kill bacteria in 10 min at 2 μg/mL of I 2 . Although KI 3 and the commercially available povidone‑iodine (I 2 -PVP) solutions show similar antibacterial efficacy, the high affinity of I 2 to SS largely enhances the shelf stability of the I 2 -SS solution with ~75 % I 2 left after one-week storage at room temperature. In sharp contrast, ~8 % and ~ 3 % I 2 are detected in KI 3 and I 2 -PVP solutions, respectively. Mechanistic study reveals that the potent antibacterial effect of I 2 -SS originates from its attack on multiple bacterial targets. The outstanding antibacterial activity, capability of accelerating wound healing, and good biocompatibility of I 2 -SS are verified through further in vivo experiments. This work may promote the development of next-generation iodine-based antiseptics for clinical use.
研究领域:
药学
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材料科学
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化学
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微生物学
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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 NANOBIOTECHNOLOGY
·
2020
·Vol. 18
·期 1
·1-13
·
IF 6.518
Zhu Guanchen,Wang Kaikai,Qin Haixiang,Zhao Xiaozhi,Chen Wei,Xu Linfeng,Cao Wenmin,Guo Hongqian
Background Chemotherapy is a standard cancer treatment which uses anti-cancer drugs to destroy or slow the growth of cancer cells. However, chemotherapy has limited therapeutic effects in bladder cancer. One of the reasons of this resistance to chemotherapy is that higher levels of glutathione in invasive bladder cancer cells. We have fabricated nanoparticles that respond to high concentrations of glutathione and near-infrared laser irradiation in order to increase the drug accumulation at the tumor sites and combine chemotherapy with photothermal therapy to overcome the challenges of bladder cancer treatment. Methods The DOX&IR780@PEG-PCL-SS NPs were prepared by co-precipitation method. We investigated the tumor targeting capability of NPs in vitro and in vivo. The orthotopic bladder cancer model in C57BL/6 mice was established for in vivo study and the photothermal effects and therapeutic efficacy of NPs were evaluated. Results The DOX&IR780@PEG-PCL-SS NPs were synthesized using internal cross-linking strategy to increase the stability of nanoparticles. Nanoparticles can be ingested by tumor cells in a short time. The DOX&IR780@PEG-PCL-SS NPs have dual sensitivity to high levels of glutathione in bladder cancer cells and near-infrared laser irradiation. Glutathione triggers chemical structural changes of nanoparticles and preliminarily releases drugs, Near-infrared laser irradiation can promote the complete release of the drugs from the nanoparticles and induce a photothermal effect, leading to destroying the tumor cells. Given the excellent tumor-targeting ability and negligible toxicity to normal tissue, DOX&IR780@PEG-PCL-SS NPs can greatly increase the concentration of the anti-cancer drugs in tumor cells. The mice treated with DOX&IR780@PEG-PCL-SS NPs have a significant reduction in tumor volume. The DOX&IR780@PEG-PCL-SS NPs can be tracked by in vivo imaging system and have good tumor targeting ability, to facilitate our assessment during the experiment. Conclusion A nanoparticle delivery system with dual sensitivity to glutathione and near-infrared laser irradiation was developed for delivering IR780 and DOX. Chemo-photothermal synergistic therapy of both primary bladder cancer and their metastases was achieved using this advanced delivery system.
研究领域:
癌症治疗
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纳米技术
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药学
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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
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Cihui Tian,Sajid Asghar,Ziyi Hu,Yue Qiu,Jingwei Zhang,Feng Shao,Yanyu Xiao
The gliomas treatment is challenging due to the limits imposed by blood-brain barrier to the distribution of the drugs in the brain. Therefore, we designed a brain glioma targeting redox-sensitive hyaluronic acid (HA)-ss-curcumin (CUR) micelles . HA was conjugated to CUR through a disulfide bond , which could form micelles independently in aqueous solution. And we further increased the drug loading by loading free CUR. Brain penetration was achieved with Tween 80, whereas glioma-targeting was inclined by CD44-mediated endocytosis . Compared to the disulfide-free group, the redox-sensitive micelles exhibited rapid in vitro drug release under high glutathione conditions, significantly enhanced cell apoptosis and cellular uptake in G422 glioma cells. Redox-sensitive micelles displayed about 4.70-fold higher area under the curve in rats after intravenous injection in comparison to the free CUR and effectively accumulated in the brain. These findings suggest that redox-sensitive micelles could be a promising candidate to achieve brain targeted CUR delivery.
研究领域:
药剂学
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肿瘤学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Shuang Yang,Beibei He,Cuiping He,Fengye Zhao,Ran Li,Minfei Shi,Bin Zheng
As a potential drug, antisense oligonucleotides (AO) have considerable application prospects in the field of tumor treatment. However, the main problem to be solved is the lack of an efficient and safe carrier that contributes to reaching the target cancer cells and utilizing the antitumor effect of AO. Here, we designed and developed a novel AO delivery system, which was based on a modified polyethylenimine (PEI) named TPGS-SS-PEI by connecting tocopherol polyethylene glycol succinate (TPGS) to PEI through the disulfide bond (SS) and the biomimetic red blood cell membrane vesicles (RVs). R-TSP/AO was composed of an AO-loaded micelle (TSP/AO) as the “core” prepared by TPGS-SS-PEI, and RVs as the “shell”. The formulations and properties of R-TSP/AO were optimized and characterized. The mean particle size and zeta potential of R-TSP/AO were 109.7 nm and −24.10 mV, respectively. In vitro studies indicated that R-TSP/AO was sensitive to highly reducing conditions and exhibited excellent stability and high security. In addition, R-TSP showed higher AO transfection efficiency and excellent gene silencing efficiency compared with unmodified PEI (P < 0.001). R-TSP/AO exhibited potent tumor inhibition (55.65%) in 4T1 tumor-bearing mice without inducing systemic toxicity. These findings suggested that R-TSP/AO was safe and efficient in enhancing the antitumor efficacy and R-TSP had the potential to be further researched as a carrier for nucleic acid drugs delivery.
研究领域:
药剂学
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纳米技术
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分子治疗学
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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
Advanced Science
·
2024
·
IF 14.3
Weiguo Song,Hekai Yang,Ying Wang,Shuzhen Chen,Wenda Zhong,Qian Wang,Wenshuo Ding,Guangzhao Xu,Chen Meng,Ying Liang,Zhe-Sheng Chen,Shuhua Cao,Liuya Wei,Fahui Li
Multi-drug resistance (MDR) is a major cause of cancer therapy failure. Photodynamic therapy (PDT) is a promising modality that can circumvent MDR and synergize with chemotherapies, based on the generation of reactive oxygen species (ROS) by photosensitizers. However, overproduction of glutathione (GSH) by cancer cells scavenges ROS and restricts the efficacy of PDT. Additionally, side effects on normal tissues are unavoidable after PDT treatment. Here, to develop organic systems that deliver effective anticancer PDT and chemotherapy simultaneously with very little side effects, three GSH-sensitive photosensitizer-drug conjugates (CyR-SS-L) are designed and synthesized. CyR-SS-L localized in the mitochondria then is cleaved into CyR-SG and SG-L parts by reacting with and consuming high levels of intracellular GSH. Notably, CyR-SG generates high levels of ROS in tumor cells instead of normal cells and be exploited for PDT and the SG-L part is used for chemotherapy. CyR-SS-L inhibits better MDR cancer tumor inhibitory activity than indocyanine green, a photosensitizer (PS) used for PDT in clinical applications. The results appear to be the first to show that CyR-SS-L may be used as an alternative PDT agent to be more effective against MDR cancers without obvious damaging normal cells by the combination of PDT, GSH depletion, and chemotherapy.
研究领域:
肿瘤学
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药学
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生物医学工程
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ChemPlusChem
·
2016
·Vol. 81
·期 11
·1237-1244
·
IF 2.836
Pei Zhang,Wenxiu He,Huiyuan Zhang,Chunzhi Huang,Dujuan Zhao,Yuxia Luan
Graphical Critical micelles concentrate on cancer : Mixed micelles made of a disulfide-linked drug–polymer conjugate and a polymer–folate conjugate were tested as a targeted, redox-sensitive delivery system (PEG–PBLG-SS-DTX/PEG–FA) for the anticancer drug docetaxel (DTX). The results showed improved anticancer efficiency of DTX delivered by these micelles to folate-receptor-expressing MCF-7 cancer cells. The objective of this study was to build mixed micelles based on two functional co-polymers, including the redox-sensitive polymer–drug conjugate methoxy poly(ethylene glycol)–poly(γ-benzyl l -glutamate)-disulfide-docetaxel (PEG–PBLG-SS-DTX) and the actively targeting methoxy poly(ethylene glycol)–folic acid (PEG–FA), for enhanced target specificity and improved anticancer efficiency of docetaxel (DTX). The spherical PEG–PBLG-SS-DTX/PEG–FA mixed micelles prepared by the dialysis method revealed a narrowly distributed size at 129.7±2.1 nm with low polydispersity of 0.10±0.02. Furthermore, the critical micelle concentration of the mixed micelles was 5.08 μg mL −1 , indicating excellent self-assembly ability in water and stability against dilution in blood circulation. The in vitro release study revealed that the conjugated DTX was rapidly released in response to dl -dithiothreitol (DTT), a reducing agent. Only 12.3 % of DTX was released from the mixed micelles after 120 h in the absence of DTT. However, the accumulative release of DTX dramatically accelerated and reached more than 40 % in 120 h after addition of DTT. The in vitro cytotoxicity, cellular uptake and cell apoptosis experiments on the mixed micelles were performed using MTT assay, fluorescence inverted microscopy and flow cytometric analysis, and 4′,6-diamidino-2-phenylindole (DAPI) staining, respectively, on folate receptor (FR)-negative A549 and FR-positive MCF-7 cells. The mixed micelles could be taken up efficiently by MCF-7 cells by FR-mediated endocytosis compared with PEG–PBLG-SS-DTX micelles. Furthermore, remarkable cytotoxicity and cell apoptosis were identified for the mixed micelles against MCF-7 cells, which was consistent with the results of the cellular uptake study. On the basis of these results, the redox-sensitive PEG–PBLG-SS-DTX/PEG–FA mixed micelles using FA as a targeting ligand revealed prominent antitumor efficiency and might be a latent drug carrier for cancer chemotherapy.
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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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Yue Yang,Yunjian Li,Kai Chen,Ling Zhang,Sen Qiao,Guoxin Tan,Fen Chen,Weisan Pan
Purpose Poor site-specific delivery and insufficient intracellular drug release in tumors are inherent disadvantages to successful chemotherapy. In this study, an extraordinary polymeric micelle nanoplatform was designed for the efficient delivery of paclitaxel (PTX) by combining dual receptor-mediated active targeting and stimuli response to intracellular reduction potential.Methods The dual-targeted redox-sensitive polymer, folic acid-hyaluronic acid-SS-vitamin E succinate (FHSV), was synthesized via an amidation reaction and characterized by 1H-NMR. Then, PTX-loaded FHSV micelles (PTX/FHSV) were prepared by a dialysis method. The physiochemical properties of the micelles were explored. Moreover, in vitro cytological experiments and in vivo animal studies were carried out to evaluate the antitumor efficacy of polymeric micelles.Results The PTX/FHSV micelles exhibited a uniform, near-spherical morphology (148.8 ± 1.4 nm) and a high drug loading capacity (11.28% ± 0.25). Triggered by the high concentration of glutathione, PTX/FHSV micelles could quickly release their loaded drug into the release medium. The in vitro cytological evaluations showed that, compared with Taxol or single receptor-targeted micelles, FHSV micelles yielded higher cellular uptake by the dual receptor-mediated endocytosis pathway, thus leading to significantly superior cytotoxicity and apoptosis in tumor cells but less cytotoxicity in normal cells. More importantly, in the in vivo antitumor experiments, PTX/FHSV micelles exhibited enhanced tumor accumulation and produced remarkable tumor growth inhibition with minimal systemic toxicity.Conclusion Our results suggest that this well-designed FHSV polymer has promising potential for use as a vehicle of chemotherapeutic drugs for precise cancer therapy.
研究领域:
药剂学
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肿瘤学
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生物材料
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yanan Chen,Zhonghao Jiang,Zhuo Yan,Jierong Liu,Yilin Lai,Li Li,Xiao Lin,Jiantao Lin
Sorafenib (SF) is a first-line drug for the treatment of hepatocellular carcinoma (HCC) in clinical practice. However, acquired drug resistance tremendously limits the clinical efficacy of sorafenib in treating HCC, which has attracted great attention. PDL1 plays a crucial role in the drug resistance of HCC. Here, a codelivery system based on poly-SS-lysine modified chitosan (TAT-C-SS-P) was established and was applied to deliver sorafenib and PDL1-siRNA for synergetic HCC therapy. The successful synthesis of TAT-C-SS-P was confirmed by 1 H NMR. Additionally, sorafenib and PDL1-siRNA were successfully transported into the cells as the decreased expression of VEGF and PD-L1 by administrated with TAT-C-SS-P@SF@ PDL1-siRNA. Simultaneously, the expression of pro-apoptosis proteins cyt-c and Bax was prominently augmented, whereas the expression of anti-apoptosis protein Bcl-2 was decreased. The reduced expression of PDL1 resulted in the downregulation of P-GP and MRP1, which contributed to more sorafenib aggregation in tumor cells. Moreover, TAT-C-SS-P@PDL1-siRNA@SF efficiently promotes apoptosis of HepG2-SI cells, as the apoptosis rate rised to 73 %. A sorafenib-insensitive model was established to evaluate in vivo antitumor effect of TAT-C-SS-P@PDL1-siRNA@SF. TAT-C-SS-P@PDL1-siRNA@SF showed a tumor inhibition rate of 90.2 ± 3.5 % and no significant decrease in body weight. Taken together, our study provided compelling evidence that TAT-C-SS-P@PDL1-siRNA@SF has great potential application in the treatment of HCC clinically.
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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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Rong Chen,Xiangrong Dai,Rongjiao Sun,Yi Liao,Jiajia Dong,Ying Tan,Xuru Jin
Acute Lung Injury (ALI) is a clinical syndrome associated with various respiratory diseases and injuries. While inhalable drug delivery systems offer the advantage of direct pulmonary targeting and reduced systemic toxicity, their therapeutic efficacy is frequently compromised by the tracheobronchial mucus barrier. To address this limitation, we developed PCL-ss-PSBMA, a novel nanocarrier engineered to overcome the constraints of conventional micelle platforms, which typically depend on either hydrophilic coatings or single-response mechanisms. By integrating zwitterionic groups and disulfide bonds in a dual-functional design, PCL-ss-PSBMA achieves synergistic optimization of mucus barrier penetration and glutathione (GSH)-triggered drug release. In addition, the nanocarrier also exhibits excellent biocompatibility, further ensuring its safety in therapeutic applications. In an ALI murine model, PCL-ss-PSBMA@DEX markedly improved the delivery efficiency and utilization rate of dexamethasone (DEX) through its dual mechanisms of mucus penetration and stimulus-responsive drug release. This design not only enhances the deposition of the drug in the lungs but also achieves efficient treatment of ALI by precisely controlling drug release, demonstrating its potential as an advanced strategy for treating respiratory diseases.
研究领域:
药学
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纳米技术
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呼吸医学
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生物医学工程
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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）