MOLECULAR PHARMACEUTICS
·
2015
·
IF 4.384
Tingjie Yin,Qu Wu,Lei Wang,Lifang Yin,Jianping Zhou,Meirong Huo
A redox-sensitive prodrug, octreotide(Phe)-polyethene glycol-disulfide bond-paclitaxel [OCT(Phe)-PEG-ss-PTX], was successfully developed for targeted intracellular delivery of PTX. The formulation emphasizes long-circulation-time polymer–drug conjugates, combined targeting based on EPR and OCT-receptor mediated endocytosis, sharp redox response, and programmed drug release. The nontargeted redox-sensitive prodrug, mPEG-ss-PTX, and the targeted insensitive prodrug, OCT(Phe)-PEG-PTX, were also synthesized as controls. These polymer–PTX conjugates, structurally confirmed by 1H NMR, exhibited approximately 23 000-fold increase in water solubility over parent PTX and possessed drug contents ranging from 11% to 14%. The redox-sensitivity of the objective OCT(Phe)-PEG-ss-PTX prodrug was verified by in vitro PTX release profile in simulated reducing conditions, and the SSTRs-mediated endocytosis was demonstrated by flow cytometry and confocal laser scanning microscopy analyses. Consequently, compared with mPEG-PTX and OCT(Phe)-PEG-PTX, the OCT(Phe)-PEG-ss-PTX exhibited much stronger cyotoxicity and apoptosis-inducing ability against NCI-H446 tumor cells (SSTRs overexpression), whereas a comparable cytotoxicity of these prodrugs was obtained against WI-38 normal cells (no SSTRs expression). Finally, the in vivo studies on NCI-H466 tumor-bearing nude mice demonstrated that the OCT(Phe)-PEG-ss-PTX possessed superior tumor-targeting ability and antitumor activity over mPEG-PTX, OCT(Phe)-PEG-PTX and Taxol, as well as minimal collateral damage. This targeted redox-sensitive polymer–PTX prodrug system is promising in tumor therapy.
研究领域:
药学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
Nanoscale
·
2021
·Vol. 13
·期 9
·5094-5102
·
IF 7.79
Jing Liu,Can Wu,Guoru Dai,Feng Feng,Yuquan Chi,Keming Xu,Wenying Zhong
Tyroservatide (YSV) belongs to a class of bioactive peptides that have drawn considerable attention in the field of drug discovery, yet it displays limited potency and often requires a millimolar concentration to execute its cellular functions. To enhance the potency of the drug through a self-assembling strategy, we designed and synthesized a series of octapeptides through conjugation of YSV with a pentapeptide sequence bearing alternating hydrophobic and hydrophilic amino acids to promote their self-assembling capabilities. Initial screening for hydrogelation gave a novel octapeptide (denoted as 1-YSV hereafter) that was capable of self-assembling under physiological conditions to afford supramolecular nanofibers with enhanced anti-cancer efficacy compared to YSV itself. Interestingly, 1-YSV formed a robust co-assembly with the anticancer drug hydroxycamptothecin (HCPT) to afford 1-YSV/HCPT hydrogel, which not only greatly improved the viscoelastic properties of hydrogels, but also stabilized HCPT in the hydrogel matrix and avoided the agglomeration of drug molecules. Compared to HCPT solution, the hydrogel formulation of 1-YSV/HCPT demonstrated better efficacy against the proliferation of non-small cell lung cancer A549 cells both in vitro and in vivo. Finally, thanks to the pure amino acid-based composition, the 1-YSV/HCPT formulation exhibited excellent biocompatibility, giving a low hemolytic rate to red blood cells, with mild local tissue reactions and negligible systematic toxicities in mice.
研究领域:
药学
·
生物材料学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Xuyang Chen,Huijuan Wen,Jinrong Yao,Xin Chen,Yu Wang,Zhengzhong Shao
With exceptional photochromic and photoluminescent properties, spiropyrans have demonstrated significant potential for advanced information encryption and anti-counterfeiting applications. However, its inherent water insolubility leads to incompatibility with aqueous polymers, and even more, its ease of leaching from the matrix hinders the formation of stable stimuli-responsive platforms through direct blending with all polymers. Here, the fabrication of amphiphilic spiropyran-octapeptide molecules is reported that can spontaneously self-assemble into highly water-dispersible supramolecular nanofibers in water. These assemblies exhibit universal polymer matrix compatibility while retaining the rapid photo-responsiveness of spiropyrans. The formation of strong interactions between the supramolecular assembly and polymer chains ensures the long-term stability of the resultant stimuli-responsive materials in aqueous environments. These platforms fully preserve the base polymers’ processing properties, with silk fibroin as the matrix offering exceptional opportunities for constructing photo-responsive platforms in various forms (e.g., films, gels, fibers, and coatings) with multiple functionalities using diverse solution processing techniques. Integrating distinct photochromic and photoluminescent responses within a single format without interference, combined with environmental stability and processing flexibility, enables the creation of dual-mode, high-security encryption devices for diverse application scenarios. The outlined strategy provides innovative concepts for developing high-performance, versatile intelligent systems utilizing stimulus-responsive molecules.
研究领域:
材料科学
·
生物化学
·
信息加密
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2016
·
IF 3.994
Hui-Yun Zhang,Wen-Qian Xu,Yuan-Wen Wang,Emmanuel Omari-Siaw,Yan Wang,Yuan-yuan Zheng,Xia Cao,Shan-Shan Tong,Jiang-nan Yu,Xi-ming Xu
Periplogenin (PPG), a cardiac glycoside prepared from Cortex periplocae , with similar structure to bufalin , has been found to induce apoptosis in many tumor cells. However, lots of cardiac glycosides possessing strong antitumor activity in vitro have still not passed phase I clinical trials , mostly due to poor tumor selectivity and systemic toxicity. To overcome this drawback, we designed octreotide-periplogenin (OCT-PPG) conjugate by coupling PPG–succinate to the amino-terminal end of octreotide . In comparison with free PPG, the conjugate exhibited significantly stronger cytotoxicity on HepG2 cells (SSTRs overexpression) but much less toxicity in L-02 cells. After intravenous injection of OCT-PPG conjugate into H 22 tumor-bearing mice, its total accumulation in tumor was 2.3 fold higher than that of free PPG, but was 0.71- and 0.84-fold lower in heart and liver, respectively, suggesting somatostatin-mediated target delivery of PPG into the tumor tissue and reduced distribution in heart and liver. In vivo studies using H 22 tumor model in mice confirmed the remarkable therapeutic effect of this conjugate. These results suggested that OCT-PPG conjugate could provide a new approach for clinical application of cardiac glycosides and as a targeting agent for cancer therapy.
研究领域:
药理学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Shasha Li,Yining Li,Ting Yu,Xinwei Wei,Yuyan Zhang,Bo Chen,Shuyi Si,Yanni Xu,Maoluo Gan
Two cyclic octadepsipeptides, microascusins A and B ( 1 and 2 ), were identified from the marine sponge-associated Microascus croci IMB19-064 co-cultivated with Escherichia coli . Their structures and conformations in solution were determined by comprehensive spectroscopic data analysis. The absolute configurations of amino and hydroxy acids were determined by the advanced Marfey’s and O -Marfey’s methods, respectively, as well as chiral-phase HPLC analysis. Microascusins A ( 1 ) and B ( 2 ) represent a new type of cyclic octadepsipeptides characterized by the presence of the unique hydroxy acid l -2-hydroxy-4-cyanobutyric acid. Compound 1 exhibited potent in vitro antiosteoporotic activity with dual regulation effects of promoting the osteoblast-mediated bone formation as well as inhibiting the RANKL-induced osteoclast differentiation at the concentration of 0.1–10 nM. Further in vivo study showed that compound 1 could improve bone mineralization after dexamethasone-induced bone damage in zebrafish through up-regulating the expression of the osteoblast-specific genes Bmp2 and Oc .
研究领域:
药理学
·
生物化学
·
天然产物化学
✓ 已验证
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2018
·
IF 5.667
Ting Yin,Sheng Zhang,Mengxuan Li,Carl Redshaw,Xin-Long Ni
Supramolecular p K a shifts, have attracted much attention in catalytic and biomimetic studies because of their excellent property to modify the acidity or basicity of the substrate in aqueous media by host-guest inclusion. Here, Fluorescence indicator displacement based on cucurbit[8]uril encapsulation of the dye acridine leads to the recognition of the peptide drug octreotide in aqueous solution via distinctive pH signals was expolited. This is thought to be a result of competitive host-guest interactions involving a supramolecular p K a shift.
研究领域:
生物化学
·
药物化学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2012
·
IF 7.404
Meirong Huo,Aifeng Zou,Chengli Yao,Yong Zhang,Jianping Zhou,Jing Wang,Qinnv Zhu,Jing Li,Qiang Zhang
In this study, a ligand-PEG-lipid conjugate , octreotide-polyethene glycol-deoxycholic acid (OCT(Phe)-PEG-DOCA, or OPD) was successfully synthesized and used as a targeting molecule for N-deoxycholic acid-O, N-hydroxyethylation chitosan (DAHC) micelles for efficient cancer therapy. DAHC micelles exhibited good loading capacities for doxorubicin (DOX), a model anti-cancer drug, and the modification of OPD showed no significant effect on drug load while slightly increasing the particle size and partly shielding the positive charges on the surface of micelles. Accelerated release rate of DOX from micelles were also observed after OPD modification and the release profile exhibited pH-sensitive properties. Compared with DAHC-DOX micelles, OPD-DAHC-DOX micelles exhibited significantly stronger cytotoxicity to MCF-7 cells (SSTRs overexpression) but with hardly any difference from WI-38 cells (no SSTRs expression). The results of flow cytometry and confocal laser scanning microscopy further revealed that OPD-DAHC-DOX micelles could be selectively taken into tumor cells by SSTRs-mediated endocytosis . In vivo investigation of micelles on nude mice bearing MCF-7 cancer xenografts confirmed that OPD-DAHC micelles possessed much higher tumor-targeting capacity than the DAHC control and exhibited enhanced anti-tumor efficacy and decreased systemic toxicity. These results suggest that OPD-DAHC micelles might be a promising anti-cancer drug delivery carrier for targeted cancer therapy.
研究领域:
药剂学
·
肿瘤学
·
生物材料
✓ 已验证
DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2022
·
IF 8.022
Peng Ma,Rongrong Huang,Yu Ou
Soy glycinin derived octapeptide (SGP8) is a peptide obtained from degradation of the soy glycinin, whose amino acid sequence is IAVPGEVA. To determine the effect of SGP8 on non-alcoholic fatty liver disease (NAFLD), steatosis HepG2 cells were induced by 1 mmol/L free fatty acid (FFA) and C57BL/6J mice were fed with methionine-choline deficient (MCD) diet for 3 weeks to establish NAFLD model. The results of oil red O staining and total cholesterol (TC)/triglyceride (TG) contents showed that SGP8 could significantly reduce the lipid content of steatosis HepG2 cells. In vivo , SGP8 lowered plasma alanine aminotransferase (ALT) and low density lipoprotein (LDL) content, normalized hepatic superoxide dismutase (SOD) and malondialdehyde (MDA) production, and reduced the severity of liver inflammation. The results of Western blotting showed that SGP8 increased expression of Sirtuin-1 (SIRT1) and phosphorylation level of AMP activated protein kinase (AMPK) in hepatocytes. Through activation of SIRT1/AMPK pathway, SGP8 downregulated the expression of sterol regulatory element binding protein 1c (SREBP-1c) and its target genes ACC and FAS expression levels, and increased the phosphorylation level of acetyl CoA carboxylase (ACC). Furthermore, SGP8 also upregulated the expression of transcription factor peroxisome proliferator activated receptor α (PPARα), which was regulated by SIRT1/AMPK pathway, and its target gene CPT1 level. In conclusion, SGP8 might improve NAFLD by activating the SIRT1/AMPK pathway. Our data suggest that SGP8 may act as a novel and potent therapeutic agent against NAFLD.
研究领域:
药理学
·
分子生物学
·
肝病学
✓ 已验证
DOI
高影响因子
JOURNAL OF ALZHEIMERS DISEASE
·
2023
·Vol. 92
·期 4
·1413-1426
·
IF 4
He Yan,Li Junjie,Yi Liling,Li Xiaohuan,Luo Man,Pang Yayan,Wang Maoju,Li Zhaolun,Xu Mingliang,Dong Zhifang,Du Yehong
Background:Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by amyloid-β peptide (Aβ) deposition. Aβ accumulation induces oxidative stress, leading to mitochondrial dysfunction, apoptosis, and so forth. Octadecaneuropeptide (ODN), a diazepam-binding inhibitor (DBI)-derived peptide, has been reported to have antioxidant properties. However, it is unclear whether ODN has neuroprotective effects in AD. Objective:To profile the potential effects of ODN on AD. Methods:We established a mouse model of AD via microinjection of Aβ in the lateral ventricle. Utilizing a combination of western blotting assays, electrophysiological recordings, and behavioral tests, we investigated the neuroprotective effects of ODN on AD. Results:DBI expression was decreased in AD model mice and cells. Meanwhile, ODN decreased Aβ generation by downregulating amyloidogenic AβPP processing in HEK-293 cells stably expressing human Swedish mutant APP695 and BACE1 (2EB2). Moreover, ODN could inhibit Aβ-induced oxidative stress in primary cultured cells and mice, as reflected by a dramatic increase in antioxidants and a decrease in pro-oxidants. We also found that ODN could reduce oxidative stress-induced apoptosis by restoring mitochondrial membrane potential, intracellular Ca2+ and cleaved caspase-3 levels in Aβ-treated primary cultured cells and mice. More importantly, intracerebroventricular injection of ODN attenuated cognitive impairments as well as long-term potentiation in Aβ-treated mice. Conclusion:These results suggest that ODN may exert a potent neuroprotective effect against Aβ-induced neurotoxicity and memory decline via its antioxidant effects, indicating that ODN may be a potential therapeutic agent for AD.
研究领域:
神经科学
·
药理学
·
分子生物学
·
神经退行性疾病
✓ 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）