蛋白冠原位调控增强肿瘤靶向19F MRI和联合治疗

doi:10.11938/cjmr20253181

摘要/Abstract

摘要：

本文构建了一种pH响应型智能诊疗一体纳米探针．以具有¹⁹F磁共振成像（MRI）造影效果的全氟化碳纳米颗粒为核心，表面吸附牛血清白蛋白（BSA）形成蛋白冠，进一步络合单宁酸-铁（TA-Fe^III），以构建核壳结构的PP@BSA-TAFe^III纳米颗粒（NPs）探针．由于TA-Fe^III中的Fe³⁺处于不饱和配位状态，使纳米探针进入血液后可与转铁蛋白结合，形成“杂交”蛋白冠，并主动靶向肿瘤细胞膜高表达的转铁蛋白受体（TfR）．该探针可高效富集于肿瘤组织，产生强的¹⁹F-MRI信号，实现对肿瘤的高灵敏成像．进入肿瘤微环境后，在酸性条件下，释放Fe³⁺诱导铁死亡，TA-Fe^III还具有优异的光热性能，可对肿瘤进行联合治疗．该蛋白冠原位调控策略可为肿瘤精准诊疗提供新思路．

关键词: ¹⁹F磁共振成像, 铁死亡, 光热治疗

Abstract:

This study designed and constructed a pH-responsive intelligent theranostic nanoprobe. The nanoprobe utilizes perfluorocarbon nanoparticles with ¹⁹F magnetic resonance imaging (MRI) contrast capability as the core, with bovine serum albumin (BSA) adsorbed on the surface to form a “protein corona”. Furthermore, tannic acid-iron (TA-Fe^III) is complexed to create the core-shell structured PP@BSA-TAFe^III nanoparticles (NPs) probe. Owing to the unsaturated coordination state of Fe³⁺ in TA-Fe^III, the nanoprobe binds to transferrin upon entering the bloodstream, forming a “hybrid” protein corona and thereby achieving active targeting of transferrin receptors (TfR) highly expressed on the tumor cell membrane. The nanoprobe efficiently accumulates in tumor tissue and generates a strong ¹⁹F-MRI signal, enabling highly sensitive tumor imaging. Upon entry into the acidic tumor microenvironment, Fe³⁺ is released to induce ferroptosis, while TA-Fe^III exhibits excellent photothermal effects, thereby achieving synergistic therapy. This in situ regulation strategy of protein corona offers a new approach for precise tumor diagnosis and therapy.

Key words: ¹⁹F magnetic resonance imaging (¹⁹F MRI), ferroptosis, photothermal therapy

中图分类号:

O482.53

李睿鹥, 李莎, 徐秋怡, 隋美菊, 陈世桢. 蛋白冠原位调控增强肿瘤靶向¹⁹F MRI和联合治疗[J]. 波谱学杂志, 2026, 43(2): 200-213.

LI Ruiyi, LI Sha, XU Qiuyi, SUI Meiju, CHEN Shizhen. In Situ Regulation of Protein Corona for Enhanced Tumor-targeted ¹⁹F MRI and Combined Therapy[J]. Chinese Journal of Magnetic Resonance, 2026, 43(2): 200-213.

图/表 8

图1

表1

实验试剂与材料

试剂/材料名称	生产厂商	规格
十二水合磷酸氢二钠	中国医药集团有限公司	500 g
二水合磷酸二氢钠	中国医药集团有限公司	500 g
二氯甲烷	国药集团化学试剂有限公司	500 mL
甲醇	国药集团化学试剂有限公司	500 mL
单宁酸（TA）	西格玛奥德里奇贸易有限公司	100 g
聚乙烯醇（PVA）	西格玛奥德里奇贸易有限公司	250 g
罗丹明B	西格玛奥德里奇贸易有限公司	25 g
牛血清白蛋白（BSA）	阿达玛斯生命科学试剂有限公司	100 g
全氟-15-冠-5-醚（PFCE）	阿达玛斯试剂有限公司	1 g
六水合三氯化铁	上海阿拉丁生化科技股份有限公司	500 g
聚(D,L-乳酸-co-乙醇酸)（PLGA）	上海阿拉丁生化科技股份有限公司	5 g
Calcein AM/PI细胞活性与细胞毒性检测试剂盒	上海碧云天生物技术股份有限公司	500 T
苏木精&伊红（H&E）染色试剂盒	上海碧云天生物技术股份有限公司	200 T
TUNEL细胞凋亡检测试剂盒（绿色荧光）	上海碧云天生物技术股份有限公司	20 T
4',6-二脒基-2-苯基吲哚（DAPI）染色液	上海碧云天生物技术股份有限公司	10 mL
细胞计数试剂盒-8（CCK-8）	上海碧云天生物技术股份有限公司	2500 T
异硫氰酸荧光素（FITC）标记鬼笔环肽	北京索莱宝科技有限公司	300 T
2',7'-二氯荧光素二乙酸酯（DCFH-DA）	北京索莱宝科技有限公司	25 mg
无菌PBS	HyClone	500 mL
RPMI 1640基础培养基	Gibco Life Sciences	500 mL
青霉素-链霉素溶液	Gibco Life Sciences	100 mL
胰蛋白酶	Gibco Life Sciences	100 mL
TRF ELISA检测试剂盒	上海江莱生物科技有限公司	48 T
胎牛血清（FBS）	长沙赛尔博克斯生物科技有限公司	50 mL
4T1细胞	中国科学院上海细胞库	TCM32
Balb/c裸鼠	湖北贝恩特生物科技有限公司	6周龄雌性

表1

表2

图2

图3

图4

图5

图6

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仪器名称	生产厂商	型号
pH计	METTLER TOLEDO	FE20
磁力加热搅拌器	IKA	HS 7
高速离心机	Beckman Coulter	Advanti J-25
动态光散射仪	Malvern	ZetaSizer Nano-ZS90
透射电子显微镜	JEOL	JEM-2100
扫描电子显微镜	Carl Zeiss AG	Zeiss Sigma
紫外分光光度计	Thermo Fisher Scientific	Evolution 220
傅里叶变换红外吸收光谱仪	Thermo Fisher Scientific	Nicolet iS10
808 nm激光器	北京镭志威	LWIRL808
红外热成像仪	武汉红视热像科技	HS160
细胞培养箱	Thermo Fisher Scientific	HeraCell 150i
细胞计数仪	瑞沃德	C100-SE/C100
无菌操作台	Thermo Fisher Scientific	MCS Advantage
激光扫描共聚焦显微镜	Nikon	AIR/A1
酶标仪	Molecular Devices	Spectro Max 190
核磁共振波谱仪	Bruker	Ascend WB 500 MHz
微成像核磁共振谱仪	Bruker	Avance 400

蛋白冠原位调控增强肿瘤靶向¹⁹F MRI和联合治疗

In Situ Regulation of Protein Corona for Enhanced Tumor-targeted ¹⁹F MRI and Combined Therapy

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