Tumor-specific Peptide Probes and the Applications in Bioimaging

doi:10.6023/A23100448

Acta Chimica Sinica ›› 2024, Vol. 82 ›› Issue (3): 367-376.DOI: 10.6023/A23100448 Previous Articles

Review

肿瘤特异性多肽探针及其在生物成像中的应用

王博^a^,^b, 蔡向东^a^,^b^,^*(), 肖建喜^a^,^b^,^*()

a 兰州大学化学化工学院兰州 730000
b 甘肃省医用胶原蛋白工程研究中心兰州 730000

投稿日期:2023-10-13 发布日期:2024-02-02

作者简介:

王博, 兰州大学化学化工学院在读硕士生, 2020年6月于西安交通大学化学工程与工艺专业获得学士学位, 随后加入兰州大学化学化工学院肖建喜教授课题组, 主要研究方向为多肽探针的设计及其在肿瘤检测方面的应用.

蔡向东, 博士, 分别于2015年和2021年在兰州大学化学化工学院化学专业获得学士学位和博士学位, 随后在兰州大学生命科学学院从事博士后研究工作. 主要研究方向为基于多肽化学的肿瘤诊断和治疗.

肖建喜, 教授, 博士生导师. 2003年获武汉大学化学学士学位, 2009年获美国新泽西州罗格斯大学(Rutgers-New Brunswick)化学博士学位. 2009~2011年在罗格斯大学从事博士后研究工作. 2012年获聘为兰州大学教授. 主要研究领域包括生物分析化学, 生物医用材料和蛋白质工程与产业化应用等. 已发表多篇SCI期刊论文, 申请发明专利40余项.

基金资助:
国家自然科学基金(22074057); 甘肃省自然科学基金(20YF3FA025); 甘肃省自然科学基金(23JRRA1096); 中国博士后科学基金(2022M711449)

Tumor-specific Peptide Probes and the Applications in Bioimaging

Bo Wang^a^,^b, Xiangdong Cai^a^,^b(), Jianxi Xiao^a^,^b()

a College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China
b Gansu Engineering Research Center of Medical Collagen, Lanzhou 730000, China

Received:2023-10-13 Published:2024-02-02
Contact: *E-mail: caixd@lzu.edu.cn;xiaojx@lzu.edu.cn
Supported by:
National Natural Science Foundation of China(22074057); Natural Science Foundation of Gansu Province(20YF3FA025); Natural Science Foundation of Gansu Province(23JRRA1096); China Postdoctoral Science Foundation(2022M711449)

The tumor is a complex system composed of various elements, encompassing cells, extracellular matrix, and the tumor microenvironment. Each of these distinct factors plays a pivotal role in the development and progression of tumors. The specific analysis of tumor-associated cells, extracellular matrix, and tumor microenvironment is of paramount importance for precise diagnosis and targeted therapy of tumors. Peptide probes have gained substantial prominence in investigations focused on tumor-specific imaging, primarily attributed to their notable attributes, including high specificity, biocompatibility, tissue-penetrating capabilities, and straightforward preparation processes. This review comprehensively summarizes the peptide probes for specific imaging of tumor-associated cells. The specific recognition of cells was by binding various cellular markers, such as the epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), and folate receptor (FRα) for tumor cells. Additionally, the biomarkers include CD206, neurokinin-1 receptor (NK-1R), and CD11c for immune cells, along with nucleolin and integrins for tumor vascular endothelial cells. Furthermore, this comprehensive review encapsulates peptide probes designed for the specific targeting of extracellular matrix proteins and their applications in tumor-specific imaging. The focal points among these protein targets encompass pathological collagen, matrix metalloproteinases, and fibronectin. Of particular significance is the potential of pathological collagen as a highly promising extracellular matrix target for achieving tumor-specific imaging. The review comprehensively outlines tumor-specific peptide probes responsive to various factors within the tumor microenvironment. Commonly encountered responsive factors in the tumor microenvironment include mild acidity (pH), heightened enzyme activity, such as matrix metalloproteinases and cathepsin, and elevated levels of oxidative stress. It further explores their versatile applications in bioimaging. Lastly, this review discusses the clinical applications of tumor-specific peptide probes in diagnostic practices. It explores the current challenges and prospects of these peptide probes, elucidating their potential contributions to precision diagnosis and personalized treatment of tumors, including precise surgical navigation and their synergistic use with immunotherapy.

Key words: cancer, tumor microenvironment, extracellular matrix, peptide probes, biological imaging

Cite this article

Bo Wang, Xiangdong Cai, Jianxi Xiao. Tumor-specific Peptide Probes and the Applications in Bioimaging[J]. Acta Chimica Sinica, 2024, 82(3): 367-376.

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Cells	Targets	Sequences	Applications	Ref.
Tumor cells	HER2	LTVSPWY	SKBR3 cells	[27]
	EGFR	YHWYGYTPQNVI	SMMC-7721 and K562 cells	[42]
	VEGFR-3	CSDSWHYWC	HT29 cells	[29]
	Tf-R	CRTIGPSVC	glioblastoma xenograft-bearing mice	[46]
	FRα	MHTAPGWGYRLS	SKOV3 cells	[28]
	CD44	WHPWSYLWTQQA	SGC-7901, BGC-823 and MKN-28 cells	[48]
	CD133	LQNAPRS	CT-26, MA-782, UMR106 and SW480 cells	[49]
Immune cells	CD206	CSPGAKVRC	B16F10 tumor-bearing mice	[56]
Immune cells	Nrp1	CGNKRTRGC	B16BL/6 tumor-bearing mice	[57]
Endothelial cells	Nucleolin	KDEPQRRSARLSAKPAPPKPEPKPKKAPAKK	—	[62-63]
	α_vβ₃and α_vβ₅ integrin	CDCRGDCFC	MDA-MB-435 tumor-bearing mice	[64]
	Plectin-1 and integrin	KTLLPTPKRGDFKK	Panc1 tumor-bearing mice	[68]

Cells	Targets	Sequences	Applications	Ref.
Tumor cells	HER2	LTVSPWY	SKBR3 cells	[27]
	EGFR	YHWYGYTPQNVI	SMMC-7721 and K562 cells	[42]
	VEGFR-3	CSDSWHYWC	HT29 cells	[29]
	Tf-R	CRTIGPSVC	glioblastoma xenograft-bearing mice	[46]
	FRα	MHTAPGWGYRLS	SKOV3 cells	[28]
	CD44	WHPWSYLWTQQA	SGC-7901, BGC-823 and MKN-28 cells	[48]
	CD133	LQNAPRS	CT-26, MA-782, UMR106 and SW480 cells	[49]
Immune cells	CD206	CSPGAKVRC	B16F10 tumor-bearing mice	[56]
Immune cells	Nrp1	CGNKRTRGC	B16BL/6 tumor-bearing mice	[57]
Endothelial cells	Nucleolin	KDEPQRRSARLSAKPAPPKPEPKPKKAPAKK	—	[62-63]
	α_vβ₃and α_vβ₅ integrin	CDCRGDCFC	MDA-MB-435 tumor-bearing mice	[64]
	Plectin-1 and integrin	KTLLPTPKRGDFKK	Panc1 tumor-bearing mice	[68]

Extracellular matrix	Sequences	Applications	Ref.
Pathological collagen	AF647-(GPO)₉	3D cells of MDA-MB-231 and MCF-7	[77]
	CF-G₃(GPO)₄^NBGPO(GPO)₄	PC-3 tumor-bearing mice	[78]
	ROX-Ahx-(GPO)₇-D₆-NH₂	Rectal, lung, cervical and breast cancer tissue	[79]
	FAM-(GPP)₈	Leiomyoma, gastric and rectal cancer tissue	[80]
	FAM-(GOP)₁₀	Gastric, lung, colorectal and breast cancers tissue	[81]
MMP-2、MMP-9	CTTHWGFTLC	B16F10 and MDA-MB-435 tumor-bearing mice	[82-83]
MMP-14	HWKHLHNTKTFL	MDA-MB-435 xenograft model mice	[84]
MMP-14	HSVEDVS	HT1080 and A549 tumor-bearing mice	[85]
MMP-16	ASTSMLRTILGP	HT-1080 cells and imaging of the tumor model mice	[86]
Fibrin	GGGGY-dGlu-C-Hyp-3ClY-GLCYIQG-NH₂	BT-20 tumor-bearing mice	[87]
Tenascin	FHKHKSPALSPVGGG	U251 and HCT116 cells; lung cancer tissue	[88]
EDB-FN	CTVRTSADC	PC3 tumor-bearing mice	[89]
Fibronectin-fibronectin	CREKA	4T1 tumor-bearing mice	[90-91]

Extracellular matrix	Sequences	Applications	Ref.
Pathological collagen	AF647-(GPO)₉	3D cells of MDA-MB-231 and MCF-7	[77]
	CF-G₃(GPO)₄^NBGPO(GPO)₄	PC-3 tumor-bearing mice	[78]
	ROX-Ahx-(GPO)₇-D₆-NH₂	Rectal, lung, cervical and breast cancer tissue	[79]
	FAM-(GPP)₈	Leiomyoma, gastric and rectal cancer tissue	[80]
	FAM-(GOP)₁₀	Gastric, lung, colorectal and breast cancers tissue	[81]
MMP-2、MMP-9	CTTHWGFTLC	B16F10 and MDA-MB-435 tumor-bearing mice	[82-83]
MMP-14	HWKHLHNTKTFL	MDA-MB-435 xenograft model mice	[84]
MMP-14	HSVEDVS	HT1080 and A549 tumor-bearing mice	[85]
MMP-16	ASTSMLRTILGP	HT-1080 cells and imaging of the tumor model mice	[86]
Fibrin	GGGGY-dGlu-C-Hyp-3ClY-GLCYIQG-NH₂	BT-20 tumor-bearing mice	[87]
Tenascin	FHKHKSPALSPVGGG	U251 and HCT116 cells; lung cancer tissue	[88]
EDB-FN	CTVRTSADC	PC3 tumor-bearing mice	[89]
Fibronectin-fibronectin	CREKA	4T1 tumor-bearing mice	[90-91]

Responsive types	Sequences	Applications	Ref.
pH	AAEQNPIYWARYADWLFTTPLLLLDLALLVDADEGTCG	M4A4 and NM2C5 cells tumor-bearing mice	[95]
	ACEQNPIYWARYANWLFTTPLLLLNLALLVDADEGTG	Breast cancer	[96]
	ACDDQNPWRAYLDLLFPTDTLLLDLLW	MDA-MB-231, 4T1, A549 and LLC tumor- bearing mice	[97-98]
	H₆	Breast cancer tumor-bearing mice	[99]
MMP-2	PLGLAG	HT-1080 cells and HT-1080 tumor-bearing mice	[100]
	GPLGVRGK	HT29 tumor-bearing mice	[101]
	PLGVR	HT-1080 cells and HT-1080 tumor-bearing mice	[102]
	GPLGIAGQ	MCF-7, MDR and L02 cells and tumor- bearing mice	[103]
MMP-14	RS-Cit-G-HPhe-YLY	U87 cells and U87 tumor-bearing	[104]
Cathepsin B	GFLG	HeLa cells and H640 tumor-bearing	[105]
Cathepsin S	PMGLP	HPAC tumor-bearing	[107]
GSH	e4(Ce4)-S-S-YHWYGYTPQNVI	Triple negative breast cancer tumor-bearing	[108]
Multi- responsiveness	MMP-2: GPLGVRG, MMP-7: VPLSLTMG	HepG2 and HL7702	[110]
	pH: R₉, MMP-2: PLGLAG	Glioma distribution in mice	[111]
	pH: HLAH-LAHHLAHLAH, MMP-2: GPLGIAGQC	U87 cells	[112]

肿瘤特异性多肽探针及其在生物成像中的应用

Tumor-specific Peptide Probes and the Applications in Bioimaging

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⁶⁴Cu DOTA-TATE Detectnet^®	neuroendocrine tumors
⁶⁸Ga PSMA-11	prostate cancer
Piflufolastat F18 injection Pylarify^®	prostate cancer

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