MOLECULAR PHARMACEUTICS
·
2013
·
IF 4.57
Xi Zhu,Wei Shan,Peiwen Zhang,Yun Jin,Shan Guan,Tingting Fan,Yang Yang,Zhou Zhou,Yuan Huang
Sufficient mucosal permeability is the bottleneck problem in developing an efficient intestinal delivery system of insulin. Cell-penetrating peptide-based nanocomplexes for the enhanced mucosal permeation of insulin were developed in this study. Penetratin, a cell-penetrating peptide was site-specifically modified with a bis-β-cyclodextrin group. Insulin-loaded nanocomplexes were prepared by self-assembly using penetratin or its bis-β-cyclodextrin modified derivative (P-bis-CD). A stronger intermolecular interaction and higher complex stability were observed for P-bis-CD nanocomplexes than the penetratin nanocomplexes. P-bis-CD nanocomplexes were significantly more efficient for the permeation of insulin as compared to the penetratin nanocomplexes both in vitro and in situ. Interestingly, different cellular internalization mechanisms were observed for the two nanocomplexes. In diabetic rats, intestinal administration of P-bis-CD nanocomplexes resulted in a prominent hypoglycemic effect which lasted for 6 h with maximum inhibitory rate at 60%. The relative pharmacological availability and bioavailability of P-bis-CD nanocomplexes were 10.6% and 7.1%, which were 3.0-fold and 2.3-fold higher than that of penetratin nanocomplexes, respectively. In addition, no sign of toxicity was observed after 7 consecutive days of administration of P-bis-CD nanocomplexes with endotoxin. These results demonstrated that P-bis-CD was a promising epithelium permeation enhancer for insulin and suggested that the chemical modification of cell penetration peptides was a feasible strategy to enhance their potential.
研究领域:
药学
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纳米技术
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药物递送系统
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-22
·
IF 12.6
Jiang Luyang,Liu Jinxia,Chen Silong,Cui Wenyu,Guo Jiarui,Cheng Xiaoyu,Zheng Yingying,Yang Wenxin,Pan Zicai,Wang Yao,Zhao Mary,Han Haijie,Yao Ke,Yu Yibo
Oxidative stress, which results from the accumulation of free radicals, plays a substantial role in cataract formation. Antioxidants have shown promise in mitigating or even preventing this process. However, delivering antioxidants noninvasively to the anterior segment of the eye has been a significant challenge. In this study, we developed ceria nanoparticles modified with cyclic cell-penetrating peptides to overcome the obstruction of the dense corneal barrier on topical drug delivery. Our results demonstrated that modified ceria nanoparticles with cell-penetrating peptides (CPPs) facilitate the opening of tight junctions in human corneal epithelial cells. This characteristic considerably enhances the trans-corneal transport of nanoparticles and improves cellular uptake efficiency, while also contributing to their intracellular enrichment toward mitochondria. Further experiments confirmed that the modified ceria nanoparticles effectively counteracted ferroptosis induced by oxidative stress in lens epithelial cells both in vitro and in vivo, substantially reducing cataract formation. The successful development of ceria nanoparticles modified with cyclic cell-penetrating peptides (cCPPs) opens new avenues for research in cataract prevention and treatment. Additionally, the modified ceria nanoparticles could serve as a noninvasive drug delivery system, which holds remarkable potential for advancing drug delivery in diseases affecting the anterior segment of the eye.Graphical
研究领域:
眼科学
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纳米医学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2021
·
IF 6.057
Yan Yang,Rui Li,Sichun Zhang,Xinrong Zhang
A lysosome-targeting ratiometric fluorescent nanoprobe based on cell-penetrating peptides (CPPs) and quantum dots (QDs) has been developed for monitoring pH fluctuation in living cells. The as-prepared nanoprobe is constructed by Rhodamine B labeled R 9 RGD CPPs as H + response unit and the red fluorescent QDs as reference unit to achieve ratiometric pH measurement. With the help of RhB-R 9 RGD CPPs, the nanoprobe efficiently stains lysosomes and enables discernment of lysosomal pH fluctuation in cells treated with different pH buffers and drug stimulation. The method of using dye labeled CPPs to realize functionalization of nanoparticle in one-step reported herein is expected to obtain wider applications in the detection of subcellular active substances by combining different small molecular probes and functional peptides.
研究领域:
生物化学
·
细胞生物学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2017
·
IF 6.319
Ying Wang,Yating Zhao,Yu Cui,Qinfu Zhao,Qiang Zhang,Sara Musetti,Karina A Kinghorn,Siling Wang
Oral administration of nanocarriers remains a significant challenge in the pharmaceutical sciences. The nanocarriers must efficiently overcome multiple gastrointestinal barriers including the harsh gastrointestinal environment, the mucosal layer, and the epithelium. Neutral hydrophilic surfaces are reportedly necessary for mucus permeation, but hydrophobic and cationic surfaces are important for efficient epithelial absorption. To accommodate these conflicting surface property requirements, we developed a strategy to modify nanocarrier surfaces with cationic cell-penetrating peptides (CPP) concealed by a hydrophilic succinylated casein (SCN) layer. SCN is a mucus-inert natural material specifically degraded in the intestine, thus protecting nanocarriers from the harsh gastric environment, facilitating their mucus permeation, and inducing exposure of CPPs after degradation for further effective transepithelial transport. Quantum dots doped hollow silica nanoparticles (HSQN) with a diameter around 180 nm was used as the nanocarrier and demonstrated as high as 50% loading efficacy of paclitaxel, a model drug with poor solubility and permeability. The dual layer modification strategy prevented premature drug leakage in stomach and maintained high mucus permeation (the trajectory spanned 9-fold larger area than single CPP modification). After intestinal degradation of SCN by trypsin, these nanocarriers exhibited strong interaction with epithelial membranes and a 5-fold increase in cellular uptake. Significant transepithelial transport and intestinal distribution were also observed for this dual-modified formulation. A pharmacokinetics study on the paclitaxel-loaded nanocarrier found 40% absolute bioavailability and 7.8-fold higher AUC compared to oral Taxol®. Compared with single CPP modified nanocarriers, our formulation showed increased in vivo efficacy and tumor accumulation of the model drug with negligible intestinal toxicity. In summary, sequential modification with CPP and SCN layers on HSQN offers a potential strategy to overcome the multiple barriers of the gastrointestinal tract . Statement of Significance Oral administration of nanocarriers remains a big challenge due to the multiple gastrointestinal barriers. In order to achieve both strong mucus permeation and efficient epithelial absorption, we modified the surface of silica nanoparticles with two layers: cell penetrating peptide (CPP) layer and succinylated casein (SCN) layer. The newly developed nanoformulations are demonstrated to have the following advantages: 1) versatile carrier with easy preparation, 2) high drug loading especially for poor soluble molecules, 3) reduced drug leakage in the stomach, 4) effective mucus penetration and transepithelial transport and 5) good biocompatibility, which in all indicate a great potential of this bilayer-modification strategy to facilitate the oral delivery of therapeutic agents.
研究领域:
药剂学
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生物医学工程
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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
Materials Today Bio
·
2025
·
IF 10.2
Shaozhen Wang,Chen Yang,Yuanyuan Zhang,Yi Hu,Lan Xiao,Weiping Ding,Bensheng Qiu,Fenfen Li
Cancer immunotherapy encounters challenges of a low treatment response rate due to the tumor immunosuppressive microenvironment and immune-related adverse events caused by off-target immunotherapy agents delivered through systemic administration in clinical practice. Photodynamic therapy (PDT) offers a viable approach to improve the immunotherapy efficacy through inducing immunogenic tumor cell death and is particularly advantageous in superficial tumor treatment. Therefore, leveraging integrated nanomaterials for photo-immunotherapy appears to be an ideal strategy to improve therapeutic outcome. In this study, we develop a transdermal-enhancing peptide (TD)-modified cationic liposome that simultaneously encapsulated with photosensitizer chlorine 6 (Ce6) and immunoadjuvant CpG, denoted as Ce6/CpG@Lip-TD, to mediate photo-immunotherapy of superficial tumors via the skin. The functionalization of TD peptide and positively charged surface endow the liposomes enhanced skin penetration capability. The combination of Ce6 and CpG within the liposomes synergistically potentiates the photo-immunotherapy effect when exposed to laser irradiation. In both melanoma and breast cancer murine models, Ce6/CpG@Lip-TD demonstrated substantial tumor-suppressing properties, along with an augmented systemic immune response against distal tumors. As a topical therapeutic agent, Ce6/CpG@Lip-TD circumvents the regulatory challenges associated with the systemic delivery of nanomaterials and significantly reduces systemic side effects, holding great promise for rapid translation into clinical applications.
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
ACS Nano
·
2024
·
IF 15.8
Peng Xu,Simei Zhong,Yunfei Wei,Xinxin Duan,Meng Zhang,Wei Shen,Yan Ma,Yu-Hui Zhang
Super-resolution fluorescence microscopy has emerged as a powerful tool for studying endoplasmic reticulum (ER) dynamics in living cells. However, the lack of high-brightness, high-photostability, and stable labeling probes makes long-term super-resolution imaging of the ER still challenging. Herein, we reported a surface-functionalized Halo-tag gold nanofluorescent probe (GNP-Atto565-fR8-CA) that exhibits excellent brightness, photostability, and biocompatibility. GNP-Atto565-fR8-CA can simultaneously load multiple Atto565 dye molecules, significantly improving its brightness. Modifying the cell-penetrating peptide fR8 enables GNP-Atto565-fR8-CA to be efficiently delivered into the cytoplasm, overcoming the challenge of their easy entrapment in vesicles. Fluorescent labeling of ER proteins via Halo tags enables high specificity and stable labeling of GNP-Atto565-fR8-CA to the ER. The SIM super-resolution imaging results showed that GNP-Atto565-fR8-CA can track and observe the long-term dynamic process of the ER, and can also be used for long-term super-resolution imaging of the dynamic interactions between the ER and other organelles. This work offers a practical tool to study live-cell ER ultrastructure and dynamics.
研究领域:
细胞生物学
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分子影像学
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生物化学
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产品关联
DOI
PubMed
高影响因子
VETERINARY RESEARCH
·
2018
·Vol. 49
·期 1
·1-9
·
IF 2.903
Hu Gaowei,Zheng Wenlv,Li Ao,Mu Yaru,Shi Mingyu,Li Tuofan,Zou Haitao,Shao Hongxia,Qin Aijian,Ye Jianqiang
Cell-penetrating peptide (CPP) is a promising cargo for delivering bioactive molecules. In this study, the N terminus of VP1 from chicken anemia virus, designated as CVP1, was found to carry enriched arginine residues with α-helix. By confocal imaging, flow cytometry and MTT assay, we identified CVP1 as a novel, safe and efficient CPP. CVP1-FITC peptide could entry different types of cells tested with dose dependence, but without cytotoxic effects. Compared with TAT-FITC peptide, the CVP1-FITC peptide showed much higher cell-penetrating activity. Moreover, CVP1 could successfully deliver β-glycosidase, poly (I:C) and plasmid into HCT116 cells. Inhibitors and temperature sensitivity analysis further indicated that the cell-penetrating activity of CVP1 was based on ATP-dependent and caveolae-mediated endocytosis. All these data demonstrate that CVP1 has efficient cell-penetrating activity and great potential for developing a novel delivery vector.
研究领域:
分子生物学
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药学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2020
·Vol. 18
·期 1
·1-16
·
IF 6.518
Guo Fangyuan,Fu Qiafan,Zhou Kang,Jin Chenghao,Wu Wenchao,Ji Xugang,Yan Qinying,Yang Qingliang,Wu Danjun,Li Aiqin,Yang Gensheng
Background Specific targeting ability and good cell penetration are two critical requirements of tumor-targeted delivery systems. In the present work, we developed a novel matrix metalloprotein-triggered, cell-penetrating, peptide-modified, star-shaped nanoparticle (NP) based on a functionalized copolymer (MePEG-Peptide-Tri-CL), with the peptide composed of GPLGIAG (matrix metalloprotein-triggered peptide for targeted delivery) and r9 (cell-penetrating peptide for penetration improvement) to enhance its biological specificity and therapeutic effect.Results Based on the in vitro release study, a sustained release profile was achieved for curcumin (Cur) release from the Cur-P-NPs at pH 7.4. Furthermore, the release rate of Cur was accelerated in the enzymatic reaction. MTT assay results indicated that the biocompatibility of polymer NPs (P-NPs) was inversely related to the NP concentration, while the efficiency toward tumor cell inhibition was positively related to the Cur-P-NP concentration. In addition, Cur-P-NPs showed higher fluorescence intensity than Cur-NPs in tumor cells, indicating improved penetration of tumor cells. An in vivo biodistribution study further demonstrated that Cur-P-NPs exhibited stronger targeting to A549 xenografts than to normal tissue. Furthermore, the strongest tumor growth inhibition (76.95%) was observed in Cur-P-NP-treated A549 tumor xenograft nude mice, with slight pulmonary toxicity.Conclusion All results demonstrated that Cur-P-NP is a promising drug delivery system that possesses specific enzyme responsiveness for use in anti-tumor therapy.
研究领域:
药剂学
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肿瘤学
·
生物材料
✓ 已验证
DOI
PubMed
高影响因子
DRUG DEVELOPMENT RESEARCH
·
2024
·Vol. 85
·期 5
·e22241
·
IF 3.5
Xiaowen Wang,Linyu Su,Chong Niu,Xiao Li,Ruijie Wang,Bo Li,Sha Liu,Yuwen Xu
The role of KRAS mutation in non-small cell lung cancer (NSCLC) initiation and progression is well-established. However, “undruggable” KRAS protein poses the research of small molecule inhibitors a significant challenge. Addressing this, proteolysis-targeting chimeras (PROTACs) have become a cutting-edge treatment method, emphasizing protein degradation. A modified ethanol injection method was employed in this study to formulate liposomes encapsulating PROTAC drug LC-2 (LC-2 LPs). Precise surface modifications using cell-penetrating peptide R8 yielded R8-LC-2 liposomes (R8-LC-2 LPs). Comprehensive cellular uptake and cytotoxicity studies unveiled that R8-LC-2 LPs depended on concentration and time, showcasing the superior performance of R8-LC-2 LPs compared to normal liposomes. In vivo pharmacokinetic profiles demonstrated the capacity of DSPE-PEG2000 to prolong the circulation time of LC-2, leading to higher plasma concentrations compared to free LC-2. In vivo antitumor efficacy research underscored the remarkable ability of R8-LC-2 LPs to effectively suppress tumor growth. This study contributed to the exploration of enhanced therapeutic strategies for NSCLC, specifically focusing on the development of liposomal PROTACs targeting the “undruggable” KRAS protein. The findings provide valuable insights into the potential of this innovative approach, offering prospects for improved drug delivery and heightened antitumor efficacy.
研究领域:
肿瘤学
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药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2012
·
IF 3.212
Jianian Chen,Shaoshun Li,Qi Shen
Dual- and multi-functional drug delivery systems , especially ligand-modified nanoparticles (NPs) loaded with chemotherapeutic agents are paid much attention to due to their excellent behavior in vitro and in vivo . Bifunctional NPs (BF-NPs), which were based on PLGA–PEG and modified with folic acid and cell penetrating peptide R 7 simultaneously, were developed. BF-NPs loaded with vincristine sulfate (VCR) were prepared via the water–oil–water emulsion solvent evaporation method. BF-NPs showed favorable particle size and zeta potentials , promising drug loading and entrapment efficiency. The release of VCR from BF-NPs exhibited a biphase release manner. Cellular uptake of BF-NPs was found to be higher than that of the NPs merely modified by folic acid or R 7 . In vitro cytotoxicity, cell apoptosis and cell cycle arrest studies also revealed that BF-NPs were more potent than those of the NPs merely modified by folic acid or R 7 . Therefore, the results demonstrated that BF-NPs developed in this study could be a potential vehicle for delivering chemotherapeutic agents such as VCR and breast cancer therapy.
研究领域:
药学
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纳米技术
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Kuan Jiang,Xingyan Fan,Yang Hu,Shengyu Yao,Yu Liu,Changyou Zhan,Weiyue Lu,Gang Wei
Retinoblastoma is the most common primary intraocular malignancy in infancy with a metastases-related death risk. However, a safe and convenient treatment without enucleation is still an unmet clinical need. In this work, a cell-penetrating peptide, 89WP, was conjugated with melphalan (89WP-Mel), which achieved high tumor inhibition effects as intravitreally injected melphalan via topical instillation for the first time. Notably, the “outside-in” diffusion of instilled 89WP-Mel created a protective shield surrounding the eye, efficiently preventing tumor metastases, while the mice treated with intravitreally injected melphalan suffered more brain metastases related death. The ocular absorption of 89WP-conjugated melphalan and other small molecules , both hydrophobic and hydrophilic , occurred via non-corneal pathway with high safety and a prolonged residence duration in retina up to 24 h. The present work paves a new avenue for simultaneous intraocular tumor inhibition and extraocular metastases prevention in a safe and convenient way via topical instillation.
研究领域:
肿瘤学
·
药理学
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眼科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2021
·
IF 14.593
Lanfang Ren,Yang Gao,Yiyun Cheng
Peptides have gained increasing interests as drug candidates in modern pharmaceutical industry, however, the development of peptide drugs acting on intracellular targets is limited due to their membrane impermeability. Here, we reported the use of metal-terpyridine based coordinative dendrimer for cytosolic peptide delivery. Among the investigated transition metal ions, Mn 2+ -coordinated polymer showed the highest delivery efficiency due to balanced peptide binding and release. It showed robust efficiency in the delivery of peptides with different charge property and hydrophobicity into various primary cells. The efficiency of Mn 2+ -terpyridine based polymer is superior to cell penetrating peptides such as oligoarginines. The material also delivered an autophagy-inducing peptide derived from Beclin-1 into cells and efficiently induced autophagy in the cells. This study provides a promising alternative to cell penetrating peptides for cytosolic peptide delivery.
研究领域:
药学
·
材料科学
·
细胞生物学
✓ 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）