ADVANCED FUNCTIONAL MATERIALS
·
2018
·Vol. 28
·期 47
·1804609
·
IF 13.325
Xinxin Dai,Kai Han,Zhaoyu Ma,Heyou Han
The precise recognition of tumor tissue is the key challenge that hinders successful clinical translation of drug delivery systems. Herein, a tumor extracellular matrix orthogonal stimuli-responsive chimeric peptide is developed for logic gate controlled tumor recognition and photodynamic therapy. In vitro studies show that the negatively charged chimeric peptide is sensitive to two typical tumor hallmarks, i.e., mild acidity and matrix metalloproteinase 2 (MMP-2) simultaneously. Consequently, the chimeric peptide can undergo charge reversal from negative charge to positive charge in tumor, accelerating the cellular uptake. Specifically, the enhanced cellular uptake of chimeric peptide can be activated efficiently only in the presence of both acidity and MMP-2, endowing chimeric peptide with highly specific tumor therapy both in vitro and in vivo. This chimeric peptide based “AND” logic gate should show great potential in precise tumor therapy.
研究领域:
生物医学工程
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Healthcare Materials
·
2019
·Vol. 9
·期 1
·1901100
·
IF 6.27
Wen Ma,Sui-Nan Sha,Pei-Ling Chen,Meng Yu,Jian-Jun Chen,Chao-Bo Huang,Bin Yu,Yun Liu,Li-Han Liu,Zhi-Qiang Yu
Nowadays, cell membrane-targeted therapy, which owns high antitumor efficacy by avoiding cell barriers, has received great attention. Here, a cell membrane-targeted self-delivery theranostic chimeric peptide CMP-PpIX is designed for simultaneously targeted photodynamic therapy (PDT) of tumor and real-time therapeutic feedback. Self-assembled CMP-PpIX nanoparticles can effectively accumulate in tumor by enhanced permeability and retention effect without additional vector. And this chimeric peptide CMP-PpIX has low background fluorescence, which is due to its relatively high intramolecular Förster resonance energy transfer (FRET) quenching efficiency between 5(6)-carboxyfluorescein (FAM) and 4-(dimethylaminoazo)-benzene-4-carboxylic acid (Dabcyl). More importantly, CMP-PpIX can be anchored on the tumor cell membrane for more than 8 h. Under irradiation, reactive oxygen species produced by CMP-PpIX directly damage cell membrane and rapidly induce apoptosis, which significantly improve the efficacy of PDT in vitro and in vivo. Then, peptide sequence Asp-Glu-Val-Asp (DEVD) is subsequently cleaved by activated caspase-3 and activated caspase-7, which separates the FAM and Dabcyl and terminates the FRET process. Therefore, fluorescence of FAM is recovered to monitor the expression of activated caspase-3 in vitro and in vivo to feedback real-time PDT therapeutic efficacy. In general, a novel cell membrane-targeted self-delivery theranostic chimeric peptide offers new promise for effective imaging-guided PDT.
研究领域:
肿瘤学
·
生物医学工程
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Kai Han,Wei-Yun Zhang,Zhao-Yu Ma,Shi-Bo Wang,Lu-Ming Xu,Jia Liu,Xian-Zheng Zhang,He-You Han
Photodynamic therapy (PDT) holds great promise in tumor treatment. Nevertheless, it remains highly desirable to develop easy-to-fabricated PDT systems with improved tumor accumulation/internalization and timely therapeutic feedback. Here, we report a tumor-acidity-responsive chimeric peptide for enhanced PDT and noninvasive real-time apoptosis imaging. Both in vitro and in vivo studies revealed that a tumor mildly acidic microenvironment could trigger rapid protonation of carboxylate anions in chimeric peptide, which led to increased ζ potential, improved hydrophobicity, controlled size enlargement, and precise morphology switching from sphere to spherocylinder shape of the chimeric peptide. All of these factors realized superfast accumulation and prolonged retention in the tumor region, selective cellular internalization, and enhanced PDT against the tumor. Meanwhile, this chimeric peptide could further generate reactive oxygen species and initiate cell apoptosis during PDT. The subsequent formation of caspase-3 enzyme hydrolyzed the chimeric peptide, achieving a high signal/noise ratio and timely fluorescence feedback. Importantly, direct utilization of the acidity responsiveness of a biofunctional Asp–Glu–Val–Asp–Gly (DEVDG, caspase-3 enzyme substrate) peptide sequence dramatically simplified the preparation and increased the performance of the chimeric peptide furthest.
研究领域:
肿瘤学
·
生物医学工程
·
分子影像学
·
药物递送
·
细胞生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2020
·Vol. 55
·期 18
·7843-7856
·
IF 3.553
Chen Pei-Ling,Shi Qun-Ying,Chen Tian,Wang Ping,Liu Yun,Liu Li-Han
Due to the low background and deep tissue penetration of near-infrared light, near-infrared fluorescence (NIRF) probes have received much attention in recent years. Cell membrane targeting probes can be used in in vitro and in vivo for living cell imaging, disease diagnosis and tumor targeted therapy. However, most of the currently available cell membrane probes are blue or green emissive fluorophores, NIRF probes are relatively rare. Herein, we designed and prepared a NIRF chimeric peptide probe named C 16 -CARK, which could target the tumor cell membrane with longtime retention (more than 4 h). Moreover, the C 16 -CARK can heat and disrupt the cell membrane upon high irradiation dose, revealing its dual roles as a cell membrane imaging probe and a photothermal agent. This kind of near-infrared fluorescence probe with cell membrane targeting and retention property provides a well design paradigm for the field of cancer imaging and treatment.
研究领域:
癌症研究
·
分子影像
·
光疗
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2018
·
IF 8.806
Hong Cheng,Rong-Rong Zheng,Gui-Ling Fan,Jing-Hao Fan,Lin-Ping Zhao,Xue-Yan Jiang,Bin Yang,Xi-Yong Yu,Shi-Ying Li,Xian-Zheng Zhang
Mitochondria and cell membrane play important roles in maintaining cellular activity and stability. Here, a single-agent self-delivery chimeric peptide based nanoparticle (designated as M-ChiP) was developed for mitochondria and plasma membrane dual-targeted photodynamic tumor therapy. Without additional carrier, M-ChiP possessed high drug loading efficacy as well as the excellent ability of producing reactive oxygen species (ROS). Moreover, the dual-targeting property facilitated the effective subcellular localization of photosensitizer protoporphyrin IX (PpIX) to generate ROS in situ for enhanced photodynamic therapy (PDT). Notably, plasma membrane-targeted PDT would enhance the membrane permeability to improve the cellular delivery of M-ChiP, and even directly disrupt the cell membrane to induce cell necrosis. Additionally, mitochondria-targeted PDT would decrease mitochondrial membrane potential and significantly promote the cell apoptosis. Both in vitro and in vivo investigations indicated that this combinatorial PDT in mitochondria and plasma membrane could achieve the therapeutic effect maximization with reduced side effects. The single-agent self-delivery system with dual-targeting strategy was demonstrated to be a promising nanoplatform for synergistic tumor therapy.
研究领域:
生物医学工程
·
癌症研究
·
分子生物学
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2019
·
IF 10.273
Hong Cheng,Jing-Hao Fan,Lin-Ping Zhao,Gui-Ling Fan,Rong-Rong Zheng,Xiao-Zhong Qiu,Xi-Yong Yu,Shi-Ying Li,Xian-Zheng Zhang
Targeted delivery of the drug to its therapeutically active site with low immunogenicity and system toxicity is critical for optimal tumor therapy. In this paper, exosomes as naturally-derived nano-sized membrane vesicles are engineered by chimeric peptide for plasma membrane and nucleus targeted photosensitizer delivery and synergistic photodynamic therapy (PDT). Importantly, a dual-stage light strategy is adopted for precise PDT by selectively and sequentially destroying the plasma membrane and nucleus of tumor cells. Briefly, plasma membrane-targeted PDT of chimeric peptide engineered exosomes (ChiP-Exo) could directly disrupt the membrane integrity and cause cell death to some extent. More interestingly, the photochemical internalization (PCI) and lysosomal escape triggered by the first-stage light significantly improve the cytosolic delivery of ChiP-Exo, which could enhance its nuclear delivery due to the presence of nuclear localization signals (NLS) peptide. Upon the second-stage light irradiation, the intranuclear ChiP-Exo would activate reactive oxygen species (ROS) in situ to disrupt nuclei for robust and synergistic PDT. Based on exosomes, this dual-stage light guided subcellular dual-targeted PDT strategy exhibits a greatly enhanced therapeutic effect on the inhibition of tumor growth with minimized system toxicity, which also provides a new insight for the development of individualized biomedicine for precise tumor therapy.
研究领域:
癌症治疗
·
生物医学工程
·
纳米医学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2016
·Vol. 8
·期 12
·2620-2627
·
IF 1.915
Xiaoyun Zhang,Ying Chen,Lin Li,Hua Qiao,Rui Wang,Jingman Ni,Jieqiong You,Kaikai Ma,Chenchen Fan,Quan Fang
The objective of this research is to develop a sensitive bioanalytical method and investigate the pharmacokinetics of a new chimeric peptide (BN-9) in rats. According to the analysis criteria, a reversed phase high performance liquid chromatography method with fluorescence detection (HPLC-FLD) was established and employed in monitoring the compound in rat plasma using doxorubicin (DOX) as the internal standard (IS). Fluorescent BN-9 and IS were extracted from plasma using dehydrated alcohol. The mobile phase was composed of acetonitrile and potassium dihydrogen phosphate buffer containing 0.05% trifluoroacetic acid (TFA) (pH 7.4; 0.02 M) (30 : 70, v/v) at 0.7 mL min−1. Fluorescence detection was conducted at 490 nm (excitation wavelength) and 520 nm (emission wavelength). The lower limit of quantification (LLOQ) was 0.009 µg mL−1. The intra-batch and inter-batch precisions were less than 8.116%, and the accuracy was within 5.632%. Blood samples were collected after intravenous administration of fluorescent BN-9 at the doses of 5, 10, and 20 mg kg−1 to rats. The main pharmacokinetic parameters were obtained by non-compartmental and compartmental analysis with DAS 2.1.1 software. The t1/2α values were 9.584 ± 5.137, 8.548 ± 2.093 and 9.621 ± 0.3224 min. The results showed that the method was successfully applied to investigate the pharmacokinetic profiles of fluorescent BN-9 following intravenous administration to rats.
研究领域:
分析化学
·
药理学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 7
·1087-1095
·
IF 5.047
Ai-Nv Zhang,Wei Wu,Chi Zhang,Qiu-Yang Wang,Ze-Nan Zhuang,Han Cheng,Xian-Zheng Zhang
Photodynamic therapy (PDT) has become an effective antibiosis method for overcoming antibiotic resistance. In this study, we developed a versatile bacterial membrane-binding chimeric peptide PpIX-[PEG8-(KLAKLAK)2]2 (denoted as PPK) by conjugating a photosensitizer protoporphyrin IX (PpIX) with an antimicrobial peptide (KLAKLAK)2 (KLA) for effective photodynamic inactivation of bacteria. The chimeric peptide PPK with positively charged properties and an α-helical conformation could rapidly bind to microbial cells through electrostatic interactions and membrane insertion. Moreover, PPK could disrupt the bacterial membrane and further elicit lipid bilayer leakage to kill bacteria by toxic reactive oxygen species (ROS) generated by PpIX under 660 nm light. In vitro experiments demonstrated that cationic PPK possessed excellent antimicrobial activity against both Gram-positive bacteria Staphylococcus aureus (S. aureus) and Gram-negative bacteria Escherichia coli (E. coli). Afterward, PPK also exhibited perfect therapeutic effects on S. aureus-infected mice without any systemic side effects. This chimeric peptide PPK will show great potential for photodynamic antibiosis.
研究领域:
微生物学
·
药剂学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Yeyang Wu,Yanmei Li,Ni Yan,Jiaqi Huang,Xinyu Li,Keyan Zhang,Zhenming Lu,Ziwen Qiu,Hong Cheng
Stimulator of the interferon genes (STING) pathway is appealing but challenging to potentiate the innate anti-tumor immunity. In this work, nuclear-targeted chimeric peptide nanorods (designated as PFPD) are constructed to amplify innate immunity through localized DNA damage and STING activation. Among which, the chimeric peptide (PpIX-FFVLKPKKKRKV) is fabricated with photosensitizer and nucleus targeting peptide sequence, which can self-assemble into nanorods and load STING agonist of DMXAA. The uniform nanosize distribution and good stability of PFPD improve the sequential targeting delivery of drugs towards tumor cells and nuclei. Under light irradiation, PFPD produce a large amount of reactive oxygen species (ROS) to destroy nuclear DNA in situ , and the released cytosolic DNA fragment will efficiently activate innate anti-tumor immunity in combination with STING agonist. In vitro and in vivo results indicate the superior ability of PFPD to activate natural killer cells and T cells, thus efficiently eradicating lung metastatic tumor without inducing unwanted side effects. This work provides a sophisticated strategy for localized activation of innate immunity for systemic tumor treatment, which may inspire the rational design of nanomedicine for tumor precision therapy.
研究领域:
癌症治疗
·
纳米技术
·
免疫学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PROTEIN JOURNAL
·
2021
·Vol. 40
·期 5
·709-720
·
IF 2.371
Jiang Xuan,Zhang Xin,Fu Chao,Zhao Ruili,Jin Tianming,Liu Mengyue,Pan Chenhao,Li Liu An,Ma Jifei,Yu Enyuan,YU Xiaoxue,Hu Ye
Malignant melanoma, an increasingly common form of skin cancer, poses a significant threat to public health, especially when the disease progresses past skin lesions to the stage of advanced metastasis. In this work, a new anti-tumor peptide, temporin La (T-La), was selected from a cDNA library generated from bullfrog skin. Two new derivative antitumor peptides, T-La (S) and T-La (FS), were designed by bioinformatics analysis and coupled with the RGD small molecule peptide to create chimeric RGD peptides, (RGD-T-La [S] and RGD-T-La [FS]). Preliminary experiments showed that the new antitumor peptides had significant antitumor effects. After coupling to the chimeric RGD peptide, the targeted treatment of mouse melanoma was significantly improved. Our data demonstrate that the 4 peptides tested herein significantly inhibited the proliferation, migration, and invasion of B16F10 cells; with an increase in polypeptide concentration, the proportion of melanoma cells in the G0/G1 phase decreased or increased significantly, respectively, the reactive oxygen species (ROS) content increased significantly, the mitochondrial membrane potential decreased significantly, and the expression of pro-apoptotic Bax, Caspase-3, and Caspase-9 increased, and anti-apoptotic Bcl-2 decreased significantly. Tyr and MITF genes were significantly downregulated. In conclusion, the use of these new anti-tumor peptides, when combined with a chimeric RGD peptide, may increase ROS levels and decrease mitochondrial membrane potential by inhibiting the activity of mitochondria, thus releasing apoptosis-promoting factors in B16F10 cells. The present study describes a new potential strategy for the application of promising peptides in the treatment of various cancers.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2017
·Vol. 27
·期 25
·1700220
·
IF 12.124
Li-Han Liu,Wen-Xiu Qiu,Yao-Hui Zhang,Bin Li,Chi Zhang,Fan Gao,Lu Zhang,Xian-Zheng Zhang
The cell membrane is the most important protective barrier in living cells and cell membrane targeted therapy may be a high-performance therapeutic modality for tumor treatment. Here, a novel charge reversible self-delivery chimeric peptide C 16 –PRP–DMA is developed for long-term cell membrane targeted photodynamic therapy (PDT). The self-assembled C 16 –PRP–DMA nanoparticles can effectively target to tumor by enhanced permeability and retention effect without additional carriers. After undergoing charge reverse in acidic tumor microenvironment, C 16 –PRP–DMA inserts into the tumor cell membrane with a long retention time of more than 14 h, which is very helpful for in vivo applications. It is found that under light irradiation, the reactive oxygen species generated by the inserted C 16 –PRP–DMA would directly disrupt cell membrane and rapidly induce cell necrosis, which remarkably increases the PDT effect in vitro and in vivo. This novel self-delivery chimeric peptide with a long-term cell membrane targeting property provides a new prospect for effective PDT of cancer.
研究领域:
癌症研究
·
药学
·
生物技术
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
Applied Materials Today
·
2019
·
IF 8.013
Hong Cheng,Ping Yuan,Guiling Fan,Linping Zhao,Rongrong Zheng,Bin Yang,Xiaozhong Qiu,Xiyong Yu,Shiying Li,Xianzheng Zhang
Tumor therapeutic efficiency is largely determined by the delivery efficacy of therapeutic agent to its final target, especially for photodynamic therapy (PDT). Although plasma membrane or nuclear targeted photosensitizer delivery is considered to be a promising strategy for enhanced photodynamic tumor therapy, they have been confronted with some difficulties and challenges. In this work, the self-delivery chimeric peptide nanorods (denoted as pnPNP) are developed for plasma membrane and nucleus dual-targeted photosensitizer delivery to achieve the synergetic in situ PDT. In vitro investigations demonstrate that the dual-targeting capability benefits the efficient subcellular localization of pnPNP in plasma membrane and nucleus. Plasma membrane targeted PDT of pnPNP could improve the membrane permeability to enhance the cellular uptake, even trigger the membrane disruption and cause cell necrosis directly. Upon light irradiation, the internalized pnPNP could effectively disrupt lysosomal structures and realize the nuclear permeation for supplementary nuclear targeted PDT. Abundant experiments verify that the plasma membrane and nucleus dual-targeted PDT exhibit a far better anti-tumor effect than the single nuclear targeted PDT. This synergistic subcellular dual-targeting strategy maximizes the PDT therapeutic efficacy, which also provides a new insight for the development of advanced drug delivery systems.
研究领域:
生物医学工程
·
纳米医学
·
癌症治疗
·
分子生物学
✓ 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）