INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 17
·9698
·
IF 6.208
Dong Wan,Yujun Liu,Xinhao Guo,Jianxin Zhang,Jie Pan
To endow the polymeric prodrug with smart properties through a safe and simple method, matrix metalloproteinase (MMPs) responsive peptide GPLGVRGDG was introduced into the block copolymer to prepare TPGS3350-GPLGVRGDG-DOX&DOX micelles, where TPGS3350is D-α-tocopheryl polyethylene glycol 3350 succinate. During the doxorubicin delivery, the cleavage of the peptide chain triggers de-PEGylation, and the remaining VRGDG sequence was retained on the surface of the micelles, which can act as a ligand to facilitate cell uptake. Moreover, the cytotoxicity of TPGS3350-GPLGVRGDG-DOX&DOX micelles against 4T1 cells was significantly improved, compared with TPGS3350-GPLGVRG-DOX&DOX micelles and TPGS3350-DOX&DOX micelles. During in vivo studies, TPGS3350-GPLGVRGDG-DOX&DOX micelles exhibited good anticancer efficacy with long circulation in the body and more efficient accumulation at the tumor site. Therefore, TPGS3350-GPLGVRGDG-DOX&DOX micelles have improved antitumor activity and reduced toxic side effects. This work opens new potential for exploring the strategy of drug delivery in clinical applications.Keywords:drug delivery;peptide;micelles
研究领域:
药学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR MODELING
·
2015
·Vol. 21
·期 11
·1-7
·
IF 1.736
Zhao Dongxin,Lu Kui
Breast cancer susceptibility gene 2 (BRCA2)—a human tumor suppressor gene—is related to various malignancies such as breast and ovarian cancer. This gene can induce the key protein RAD51 recombinase, which is involved in homologous recombination with single-stranded DNA in the human body and can regulate RAD51 to complete the repair of damaged double-stranded DNA. Eight highly conserved BRC repeat motifs in BRCA2 protein serve as sites for the interaction between BRCA2 and RAD51. BRCA2 regulates RAD51 through these motifs. However, the mechanism of this interaction still requires further research. In this study, the BRC4 motif that demonstrated strong interaction with RAD51 was selected as template peptide. On the basis of known data regarding the crystal structure of the BRC4-RAD51(191–220) complex, a series of BRC4 mutants was designed using PyMOL software based on the sequence of BRC4, and polypeptides were synthesized by the Fmoc solid-phase method. After purification by reversed-phase high-performance liquid chromatography, the purity of the polypeptides reached >95 %. The primary determination of circular dichroism spectra showed that the polypeptides exhibited slight changes in secondary structure, which indicated that mutation on the non-conserved sites in BRC4 probably affected the interaction with BRC4. These findings will facilitate research on the interaction between targeting peptides and BRC4 mutants, as well the basic rules covering this interaction.
研究领域:
分子生物学
·
结构生物学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2024
·
IF 5.5
Xiaoyu Guo,Bin Yang,Junyi Chen
The preparation of polysaccharide-peptide hydrogels usually involves multiple synthetic steps, thus reducing the effectiveness and practicality of these approaches. Inspired by recent discoveries in aqueous N-carboxyanhydride (NCA) ring-opening polymerization (ROP) and ring-opening polymerization-induced nanogelation, we present an aqueous one-pot strategy to prepare polysaccharide-polypeptide hydrogels. In this study, water-soluble polysaccharide carboxymethyl chitosan is used as the macromolecular initiator to prepare polysaccharide-polypeptide copolymers through the aqueous ROP of NCA. The catalyst-free approach afforded hydrogels with properties that could be controlled by adjusting the type and amount of NCA used, with the elastic modulus ranging from 50 Pa to 18000 Pa. The hydrogen bond-cross-linked hydrogel exhibited self-healing and injectable properties. Morphology characterization revealed that micelles were formed in the early stage of reaction, suggesting that the polymerization follows an aqueous ring-opening polymerization-induced self-assembly (ROPISA) mechanism and that aggregation of micelles during the reaction caused the gelation. Moreover, the hydrogels displayed high swelling ratios (>95% water content), and hemolysis and cytotoxicity experiments demonstrated that the hydrogels had excellent biocompatibility, indicating their potential in medical applications.
研究领域:
材料科学
·
生物医学工程
·
高分子化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NANOTECHNOLOGY
·
2015
·Vol. 26
·期 49
·495102
·
IF 3.821
Ming-Hao Yao,Jie Yang,Ji-Tao Song,Lin Zhang,Bi-Yun Fang,Dong-Hui Zhao,Rui-Xue Xia,Rui-Mei Jin,Yuan-Di Zhao,Bo Liu
Quantum dot (QD)–polypeptide probes have been developed through the specific metal-affinity interaction between polypeptides appended with N-terminal polyhistidine sequences and CdSe/ZnS core–shell QDs. The size and charge of a QD–polypeptide can be tuned by using different coiled-coil polypeptides. Compared to glutathione-capped QDs (QD–GSH), QD–polypeptide probes showed an approximately two- to three-fold luminescence increase, and the luminescence increase was not obviously related to the charge of the polypeptide. QD–polypeptide probes with different charge have a great effect on nonspecific cellular uptake. QD–polypeptide probes with negative charge exhibited lower nonspecific cellular uptake in comparison to the QD–GSH, while positively charged QD–polypeptide probes presented higher cellular uptake than the QD–GSH. A targeted QD–ARGD probe can obviously increase targeted cellular uptake in αvβ3 overexpressing HeLa cells compared to QD–A. In addition, QD–polypeptide probes showed lower in vitro cytotoxicity compared to the original QDs. These results demonstrate that these QD–polypeptide probes with high specific cellular uptake, high fluorescence intensity and low background noise are expected to have great potential applications in targeted cell imaging.
研究领域:
生物化学
·
分子生物学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2020
·Vol. 30
·期 25
·2001196
·
IF 16.836
Liang Cheng,Zhengwei Cai,Tingjun Ye,Xiaohua Yu,Zhijie Chen,Yufei Yan,Jin Qi,Lei Wang,Zhihong Liu,Wenguo Cui,Lianfu Deng
Protein is the key composition of all tissues, which has also been widely used in tissue engineering due to its superior biocompatibility and low immunogenicity. However, natural protein usually lacks active functions such as vascularization, osteo-induction, and neural differentiation, which limits its further applications as a functional biomaterial. Here, based on the mimetic extracellular matrix feature of bovine serum albumin, injectable polypeptide-protein hydrogels with vascularization and antibacterial abilities are constructed successfully via coordinative cross-linking of sulfydryl groups with silver ions (Ag+) for the regeneration of infected wound. In this protein hydrogel system, (Ag+), acting as crosslinkers, can not only provide a sterile microenvironment and a strong and robust antibacterial ability but also introduce K 2 (SL) 6 K 2 (KK) polypeptide, which endows the hydrogel with vascularization behavior. Furthermore, the in vivo data show that the polypeptide-protein hydrogel has a considerable collagen deposition and vascularization abilities in the early stage of wound healing, resulting in rapid new tissue regeneration featured with newly appeared hair follicles. Altogether, this newly developed multifunctional 3D polypeptide-protein hydrogel with vascularization, antibacterial properties, and hair follicle promotion can be a promising approach in biomedical fields such as infected wound healing.
研究领域:
组织工程
·
生物材料
·
伤口愈合
·
生物医学工程
✓ 已验证
DOI
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2025
·
IF 11.9
Qinying Chen,Xinao Liu,Zijin Tan,Zhihao Liu,Zijie Qiu,Yerong Xiong,Jiasheng Tu,Yanping Wu,Chunmeng Sun
Antitumor nanomedicines are usually decorated with ligands to achieve multiple functions, such as focused targeting, tissue penetration, and enhanced cellular uptake. However, a single ligand with multiple functions is generally preferred for use in practice. Herein, a versatile peptide, (HE) 10 G 5 R 6 GDK (HE-RK), was engineered by integrating several motifs in a single sequence, including a masking segment (HE), a flexible linker (G 5 ), and a tumor-penetrating head (RK), which comprised a cell-penetrating peptide (R 6 ) and a C-end Rule peptide (RGDK). The RK moiety in HE-RK was sequentially activated following the gradual charge reversal of HE to facilitate the accumulation of its cargos in deep tumor tissue and the cytosol of cancer cells. Moreover, in our study, polymer micelles conjugated with the HE-RK peptide (PM-HE-RK) showed superior cellular internalization at pH 6.5 compared to pH 7.4 in vitro , as well as extended blood circulation time and improved tumor targeting and penetration in vivo . Furthermore, the paclitaxel (PTX)-loaded micelles (PTX/PM-HE-RK) demonstrated considerable antitumor efficacy, that is, an 81.48% tumor inhibition rate in the 4T1 mouse model. Overall, the construction of this all-in-one multisegment peptide presents a synergistic and complementary approach to advancing multifunctional peptide ligand design.
研究领域:
生物医学工程
·
癌症治疗学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY
·
2015
·Vol. 53
·期 21
·2469-2480
·
IF 3.113
Yong Deng,Xi Wang,Qiulin Yuan,Mengxiang Zhu,Ying Ling,Haoyu Tang
A series of side-chain-functionalized α-helical polypeptides, i.e., poly(γ-4-(3-chloropropoxycarbonyl)benzyl- L -glutamate) (6) have been prepared from n-butylamine initiated ring-opening polymerization (ROP) of γ-4-(3-chloropropoxycarbonyl)benzyl- L -glutamic acid-based N -carboxyanhydride. Polypeptides bearing oligo-ethylene-glycol (OEG) groups or 1-butylimidazolium salts were prepared from 6 via copper-mediated [2+3] alkyne-azide 1,3-dipolar cycloaddition or nuleophilic substitution, respectively. CD and FTIR analysis revealed that the polymers adopt α-helical conformations both in solution and the solid state. Polymers bearing OEG (m = 3) side-chains showed reversible LCST-type phase transition behaviors in water while polymers bearing 1-butylimidazolium and I − counter-anions exhibited reversible UCST-type transitions in water. Variable-temperature UV-vis analysis revealed that the phase transition temperatures ( T pt s) were dependent on the main-chain length and polymeric concentration. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53 , 2469–2480
研究领域:
高分子化学
·
生物材料
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF SOL-GEL SCIENCE AND TECHNOLOGY
·
2019
·Vol. 92
·期 3
·618-627
·
IF 1.986
Zhu Hongyu,Zhu Meng,Shuai Shirong,Zhao Cong,Liu Yu,Liu Yuan,Li Xiaohong,Rao Zikun,Li Yang,Hao Jianyuan
The delicacy of nature prompted scientists to create functional or responsive biomaterials using existing natural components. Here we reported novel thermo-gelling hydrogels based on methyl poly (ethylene glycol)-poly (L-valine) (mPEG-L-PV) diblock copolymer solutions, which exhibited well-defined sol–gel transition at a temperature range from 10 °C to 40 °C. The β-sheet was the dominant secondary structure for poly(L-PV) block when the molecular weight of the polypeptide ranged from 277 Da to 1138 Da. The formation of mPEG–L-PV clear sol solutions was related to the stable nanostructures that were aggregated clusters of poly(L-PV) β-sheet filaments and stabilized by the hydrophilic PEG segments. The block length of poly(L-PV) significantly affected the secondary structures of polypeptide and the morphology of assembled filaments, which resulted in different thermo-gelling behavior of the copolymer solutions. The occurrence of sol–gel transition with temperature was primarily due to the dehydration effect of PEG block, whereas in the case of the copolymer with a lower molecular weight of poly(L-PV) block, the change of polypeptide secondary structures also contributed to the formation of the gel. This paper provides fundamental information about the strong dependence of polypeptide block length on the nano-assembly morphology as well as thermosensitive behavior of polypeptide-based hydrogels.
The block length of poly(L-PV) significantly affected the secondary structures of polypeptide and the morphology of assembled filaments, which resulted in different thermo-gelling behavior of the copolymer solutions.
研究领域:
生物材料
·
高分子化学
·
生物物理学
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2014
·
IF 8.312
Wantong Song,Zhaohui Tang,Dawei Zhang,Ying Zhang,Haiyang Yu,Mingqiang Li,Shixian Lv,Hai Sun,Mingxiao Deng,Xuesi Chen
There are two important obstacles for the currently applied anti-cancer drug delivery systems. One is the conflict between long-circulation and cellular uptake while the other one is the achievement of ideal anti-cancer efficacy. To solve these problems, we designed a polypeptide-based micelle system that combined the advantages of receptor mediated endocytosis and multi-drug delivery. Firstly, an amphiphilic PLG- g -Ve/PEG graft copolymer was prepared by grafting α-tocopherol (Ve) and polyethylene glycol (PEG) to poly( l -glutamic acid) (PLG). Then docetaxel (DTX) and cisplatin (CDDP) were co-loaded into the PLG- g -Ve/PEG micelles via hydrophobic and chelation effect. After that, the surface of the dual-drug-loaded micelles was decorated with an α v β 3 integrin targeting peptide c(RGDfK). The targeted dual-drug-loaded micelles showed synergistic cytotoxicity and enhanced internalization rate in mouse melanoma (B16F1) cells. In vivo tests demonstrated that remarkable long circulation, anti-tumor and anti-metastasis efficacy could be achieved using this drug delivery system. This work revealed a strategy for the design and preparation of anti-cancer drug delivery systems with reduced side effect, enhanced anti-tumor and anti-metastasis efficacy.
研究领域:
药学
·
肿瘤学
·
生物材料
✓ 已验证
DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
Chunbao Du,Xiaoling Hu,Yuan Cheng,Junfeng Gao,Yong-Wei Zhang,Kehe Su,Zhijian Li,Nan Zhang,Ninghui Chang,Kaiyang Zeng
In this paper we systematically investigate the loading capacity of raspberry–like nano/microspheres with highly cross–linked structure for the peptide, immunostimulating hexapeptide from human (IHH), by integrating both experimental and simulation efforts. The experimental results indicate that the loading capacities of raspberry–like nano/microspheres with different functionalized chains vary drastically. To provide theoretical insights into the observed phenomenon, the typical raspberry–like nano/microspheres were simplified as effective functionalized groups, thereby the interactions between them and IHH were accurately calculated by ab initio method. The ab initio results agree well with the experimental observations, and the underlying binding mechanism is analyzed in great details. It is shown that hydrogen bonding plays an important role and the binding affinity strongly depends on the functionalized motifs. Therefore, this work provides insightful guidance to controlling the drug loading by design of the functionalized surface of nanomaterials.
研究领域:
生物医学工程
·
药剂学
·
计算化学
✓ 已验证
DOI
高影响因子
Polymer Chemistry
·
2013
·Vol. 4
·期 11
·3345-3356
·
IF 5.231
Jianxun Ding,Li Zhao,Di Li,Chunsheng Xiao,Xiuli Zhuang,Xuesi Chen
A series of thermo-responsive “hairy-rod” polypeptides was efficiently synthesized by grafting of azide-terminated (co)polymers of 2-(2-methoxyethoxy)ethyl methacrylate (MEO2MA) or 2-(2-(2-methoxyethoxy)ethoxy)ethyl methacrylate (MEO3MA) (i.e., N3-PMEOiMA) onto poly(γ-propargyl-L-glutamate) (PPLG) through a “click” reaction. The thermo-responsiveness and secondary structure of the resultant polypeptides (i.e. PLG-g-PMEOiMA) were shown to be dependent on the MEO2MA : MEO3MA ratio in PMEOiMA side chains. PLG40-g-P(MEO2MA18-co-MEO3MA9) (P2) and PLG40-g-P(MEO2MA7-co-MEO3MA18) (P4) with lower critical solution temperatures at 25.6 and 34.8 °C, and cloud points at 26.9 and 35.6 °C in physiological saline, respectively, were selected to self-assemble into micelles for doxorubicin (DOX) loading and release. In vitro DOX release from DOX-loaded micelles could be accelerated by a decrease of temperature and pH. Confocal laser scanning microscopy and flow cytometry confirmed the efficient internalization and intracellular DOX release of DOX-loaded micelles towards HeLa cells (a human cervical carcinoma cell line). In vitro methyl thiazolyl tetrazolium assays revealed that the polypeptides were cytocompatible, and DOX-loaded micelles showed efficient cellular proliferation inhibition. Hemolysis tests indicated that micelles were hemocompatible, and the encapsulation with polypeptides significantly reduced the hemolysis ratio of DOX. Therefore, the thermo-responsive polypeptide micelles, which are stable in physiological condition while releasing payloads in the acidic intracellular microenvironment, are promising for smart drug delivery.
研究领域:
生物材料
·
药学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Dedai Lu,Hongsen Wang,Ting’e Li,Yunfei Li,Fajuan Dou,Shaobo Sun,Hongyun Guo,Shiqi Liao,Zhiwang Yang,Qiangbing Wei,Ziqiang Lei
Inspired by marine mussel adhesive proteins, polymers with catechol side groups have been extensively explored in industrial and academic research. Here, Pluronic L-31 alcoholate ions were used as the initiator to prepare a series of polypeptide–Pluronic–polypeptide triblock copolymers via ring-opening polymerization of l-DOPA-N-carboxyanhydride (DOPA-NCA), l-arginine-NCA (Arg-NCA), l-cysteine-NCA (Cys-NCA), and ε-N-acryloyl lysine-NCA (Ac-Lys-NCA). These copolymers demonstrated good biodegradability, biocompatibility, and thermoresponsive properties. Adhesion tests using porcine skin and bone as adherends demonstrated lap-shear adhesion strengths up to 106 kPa and tensile adhesion strengths up to 675 kPa. The antibleeding activity and tissue adhesive ability were evaluated using a rat model. These polypeptide–Pluronic copolymer glues showed superior hemostatic properties and superior effects in wound healing and osteotomy gaps. Complete healing of skin incisions and remodeling of osteotomy gaps were observed in all rats after 14 and 60 days, respectively. These copolymers have potential uses as tissue adhesives, antibleeding, and tissue engineering materials.
研究领域:
生物材料
·
医学
·
高分子化学
✓ 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）