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Systemic study on anti-tumor activity of HER2 induced peptide-drug conjugate clustering in xenograft tumor models 认领 引用
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作者 Qing-Hua Chen Da-Yong Hou +21 位作者 Ni-Yuan Zhang Jia-Qi Wang Rui Zheng Xing-Jie Hu Xiu-Hai Wu Li Yi Ying-Jin Zhang Guang-Xu Zhang Yu-Juan Gao Ben-Li Song Rui Wang Jian-Xiao Liang Ming-Ze Cai Yu Wang Jia-Yuan Niu Li-Ying Wang Yang Yang Hao-Ze Li Hong-Wei An Lei Wang Yuliang Zhao Hao Wang 《Chinese Chemical Letters》 SCIE CAS CSCD 2026年第5期438-442,共5页
Target therapy represents a paradigm shift to a precise and personalized approach.Unlike the great success of antibody-drug conjugate(ADC)in clinical practice,peptide-drug conjugate(PDC)with good tissue penetration an... Target therapy represents a paradigm shift to a precise and personalized approach.Unlike the great success of antibody-drug conjugate(ADC)in clinical practice,peptide-drug conjugate(PDC)with good tissue penetration and drug loading capacity exhibits poor stability,quick blood clearance and cellular internalization that limit their translation.In this study,a feasible approach for constructing an in vivo self-assembling peptide-drug conjugate(s PDC)was proposed by rationally designing the combination of tumor-specific targeting peptide module,responsive self-assembling peptide module,and therapeutic drug.Two optimized s PDCs(s PDC1 and s PDC2)capable of specifically targeting human epidermal growth factor receptor 2(HER2)on the surface of tumors were reported.s PDCs could selectively target HER2-positive tumors and effectively kill HER2 overexpressing tumor cells.In addition,weak but significant efficacy of s PDCs was also observed in HER2-negative tumors,which was likely by-stander effect due to the release of monomethyl auristatin E(MMAE)in the tumor microenvironment.Finally,in HER2-positive xenograft mouse models,s PDC1 showed superior therapeutic efficacy over the clinical HER2-targeted therapeutic agents trastuzumab and lapatinib,and roughly equivalent therapeutic efficacy compared with RC48 even in large tumor-bearing mouse models.Therefore,s PDC1 was promising to serve as a lead compound for further clinical development for oncology therapy. 展开更多
关键词 Human epidermal growth factor receptor 2(HER2) Peptide-drug conjugate(PDC) In vivo self-assembly Monomethyl auristatin E(MMAE) Tumor-targeted therapy
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Screened peptides from one-bead one-compound technique extend half-life of peptide drugs in circulation through binding to albumin 认领 引用 被引量：1
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作者 Yi-Jing Li Lingze Zhang +7 位作者 Ming-Hao Pang Pei-Pei Yang Lu-Ming Guo Kuo Zhang Da-Yong Hou Lei Wang Hao Wang Hui Cao 《Chinese Chemical Letters》 SCIE CAS CSCD 2024年第3期384-388,共5页
Peptide drugs are known for their high biological safety.However,compared with small molecule drugs,peptide drugs are easily oxidized and hydrolyzed as well as short in half-life.Herein,inspired by the long circulatio... Peptide drugs are known for their high biological safety.However,compared with small molecule drugs,peptide drugs are easily oxidized and hydrolyzed as well as short in half-life.Herein,inspired by the long circulation of albumin in blood,we screened albumin binding peptides(ABPs)from a one-bead one-compound(OBOC)peptide library to increase the half-life of peptide drugs.Beads displaying random peptides were screened using fluorescent labeled human serum albumin.Fluorescent beads with specific binding to albumin were isolated for sequencing.The selected ABPs can effectively bind to albumin,thus possessing the long circulation of albumin.The dissociation constant(KD)of ABPs to albumin is up to 1×10-8mol/L.Once one of ABPs(ABP2)was coupled to triptorelin,the circulation half-life of triptorelin in mice was significantly prolonged to 263.50 h much longer than that of triptorelin alone(179.07 h).In addition,the combination therapy using ABP-conjugated triptorelin and doxorubicin(DOX)can effectively inhibit the proliferation of tumor cells in mice.The OBOC screening strategy and resulting ABPs showed great potential for enhancing the delivery efficiency of peptide drugs. 展开更多
关键词 One-bead one-compound Combinatorial library Albumin binding Drug delivery Triptorelin
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In vivo self-assembled bispecific fluorescence probe for early detection of bladder cancer and metastasis 认领 引用 被引量：4
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作者 Da-Yong Hou Ni-Yuan Zhang +12 位作者 Peng Zhang Xiang-Peng Li Jiong-Cheng Wu Mei-Yu Lv Zhi-Jia Wang Xing-Jie Hu Jian-Xiao Liang Hong-Lei Wang Yue-Ze Wang Hui-Hui You Hong-Wei An Hao Wang Wanhai Xu 《Science Bulletin》 SCIE EI CAS CSCD 2025年第3期407-418,共12页
Tumor metastasis accounts for over 90%of tumor-related deaths,prompting the development of fluorescently labeled tumor-specific molecular imaging agents for differentiating tumors from normal tissues.However,early det... Tumor metastasis accounts for over 90%of tumor-related deaths,prompting the development of fluorescently labeled tumor-specific molecular imaging agents for differentiating tumors from normal tissues.However,early detection of metastasis lesions by tracking tumor markers alone has proven to be challenging.Herein,we reported a glycopeptide-based bispecific fluorescence probe(bsProbe)for earlier detection of bladder cancer and metastasis.By simultaneously recognition(tumor&tumor microenvironment)and in vivo self-assembly,the tumor accumulation of bsProbe(12.3%ID/g)was obviously increased by∼6 fold compared with that in CXCR4 specific fluorescence probe(sProbe),indicating the obvious advantages of bsProbe over existing tumor metastasis detection probes.Additionally,bsProbe substantially broadens the tumor diagnosis window and enhances the detection signal to noise ratio(SNR:approximately 9.5),permitting early diagnosis of lung micro-metastasis(∼1 mm),precise identifying of tumor boundaries and micro-tumors in orthotopic tumor models.More importantly,bsProbe was demonstrated to distinguish malignant from benign specimen with a specificity of 90.48%and sensitivity of 92.22%in 195 clinical specimens of bladder cancer patients.Taken together,this novel synergetic targeting(CD206×CXCR4)strategy provides an attractive method for earlier detection of bladder cancer and metastasis,which might be further extended to the imaging-guided surgery of clinical invisible tumors. 展开更多
关键词 Self-assembly Peptide Nanomaterial Fluorescence imaging Bladder cancer
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An activated excretion-retarded tumor imaging strategy towards metabolic organs 认领 引用 被引量：5
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作者 Da-Yong Hou Man-Di Wang +8 位作者 Xing-Jie Hu Zhi-Jia Wang Ni-Yuan Zhang Gan-Tian Lv Jia-Qi Wang Xiu-Hai Wu Lu Wang Hao Wang Wanhai Xu 《Bioactive Materials》 SCIE CSCD 2022年第8期110-119,共10页
Intraoperative fluorescence-based tumor imaging plays a crucial role in performing the oncological safe tumor resection with the advantage of differentiating tumor from normal tissues.However,the application of these ... Intraoperative fluorescence-based tumor imaging plays a crucial role in performing the oncological safe tumor resection with the advantage of differentiating tumor from normal tissues.However,the application of these fluorescence contrast agents in renal cell carcinoma(RCC)and hepatocellular carcinoma(HCC)was dramatically hammered as a result of lacking active targeting and poor retention time in tumor,which limited the Signal to Noise Ratio(SNR)and narrowed the imaging window for complicated surgery.Herein,we reported an activated excretion-retarded tumor imaging(AERTI)strategy,which could be in situ activated with MMP-2 and self-assembled on the surface of tumor cells,thereby resulting in a promoted excretion-retarded effect with an extended tumor retention time and enhanced SNR.Briefly,the AERTI strategy could selectively recognize the Integrin αvβ3.Afterwards,the AERTI strategy would be activated and in situ assembled into nanofibrillar structure after specifically cleaved by MMP-2 upregulated in a variety of human tumors.We demonstrated that the AERTI strategy was successfully accumulated at the tumor sites in the 786-O and HepG2 xenograft models.More importantly,the modified modular design strategy obviously enhanced the SNR of AERTI strategy in the imaging of orthotopic RCC and HCC.Taken together,the results presented here undoubtedly confirmed the design and advantage of this AERTI strategy for the imaging of tumors in metabolic organs. 展开更多
关键词 Self-assembly Biomaging Peptide Probe Tumor
Live Cells Process Exogenous Peptide as Fibronectin Fibrillogenesis In Vivo 认领 引用 被引量：1
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作者 Ping-Ping He Xiang-Dan Li +10 位作者 Jia-Qi Fan Yu Fan Pei-Pei Yang Bing-Nan Li Yong Cong Chao Yang Kuo Zhang Zi-Qi Wang Da-Yong Hou Hao Wang Lei Wang 《CCS Chemistry》 2020年第5期539-554,共16页
The human body is one of the most sophisticated material systems.It is still a considerable challenge to biomimic the“life-design”process to construct a part of“life”in vivo.Herein,we mimicked the natural fibronec... The human body is one of the most sophisticated material systems.It is still a considerable challenge to biomimic the“life-design”process to construct a part of“life”in vivo.Herein,we mimicked the natural fibronectin(FN)fibrillogenesis system using ligand–receptor interaction-induced self-assembly to construct in situ artificial fibrous FN in vivo,based on exogenous FN mimic peptide(FNMP).We performed the in vivo study with a tumor-bearing mouse model,to which the particle formulated FNMP raw materials were delivered with high efficiency to the tumor site through intravenous(iv)administration.In the tumor,the presence of overexpressed integrin receptors on the cell surface induced the self-assembly of the FNMP into fibrous structures,thereby,creating an artificial fibrous FN.However,the FNMP-based artificial fibrous FN showed different biological functionality from the natural fibrous FN,inhibiting the growth and migration of cells,making our constructed FN able to inhibit tumor growth,invasion,and metastasis.Thus,this study opens an avenue for the precise construction of biomimetic materials for in vivo biomedical applications. 展开更多
关键词 biomimetic ligand–receptor interaction peptide self-assembly tumor
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