无机材料学报2025，Vol.40Issue(7)：754-764,中插3-中插10,19.DOI:10.15541/jim20240504
基于稀土铕离子荧光标记的磷酸钙纳米材料体内分布与代谢研究
In vivo Distribution and Metabolism of Calcium Phosphate Nanomaterials Based on Fluorescent Labeling with Rare Earth Europium Ions
摘要
Abstract
Nano-calcium phosphate(nCaP)has potential applications in nanomedicine fields such as drug delivery,bioimaging,antibacterial treatment,and bone formation promotion.However,its distribution and metabolic patterns within the body are not yet fully understood and require further in-depth research.This study employs a rare earth europium ion fluorescence labeling method and uses tumor-bearing mice as a model to investigate the distribution and metabolism of two sizes of nCaP(nanodots NDs:(2.53±0.63)nm;nanoparticles NPs:(107.76±25.37)nm×(17.66±1.63)nm)in the liver,spleen,lung,kidney,and tumor tissue.The results showed that after tail vein injection of 200 μL with a mass concentration of 1.5 mg/mL nCaP into tumor-bearing nude rats for 4 h,CaP NPs were primarily distributed in the liver and spleen,accounting for 65.70%and 29.32%,respectively,with 3.83%in the lung,while only 0.84%and 0.32%in the kidney and tumor.This suggests that larger CaP NPs are more easily captured by phagocytes within the reticuloendothelial system(RES).In contrast,compared to CaP NPs,accumulation of CaP NDs in the liver,spleen,and lung decreased significantly by 89.40%,87.00%,and 88.89%,respectively,while their accumulation in the kidney and tumor increased by 3.67 and 3.06 times.This indicates that smaller particle size facilitates CaP NDs in glomerular filtration for urinary excretion and enhances their tumor-targeting capability.The clearance rates(CLz)of CaP NDs in the liver,spleen,and lung were 6.60,4.14,and 2.40 times higher than that of CaP NPs,respectively,and 42.29%in the kidney.This indicates that reduced size of CaP NDs facilitates rapid metabolism by phagocytes in the liver,spleen,and lung but also results in reabsorption in the renal tubules.In tumor,the CLz of CaP NDs decreased by 91.9%,much smaller than that of CaP NPs,suggesting that the smaller CaP NDs exhibit significantly enhanced tumor targeting and retention capability.In the meantime,a physiologically based pharmacokinetic(PBPK)model incorporating particle size factors was preliminarily established for tumor-bearing mice to simulate the distribution of nano-calcium phosphate.The model's predictive fit(R2)for CaP NDs and CaP NPs in tumor sites reached 0.925 and 0.827,respectively.This study provides promising support for understanding in vivo distribution and metabolic patterns of nCaP and applying potential in medicine.关键词
纳米磷酸钙/尺寸效应/荧光标记/组织分布/生理药代动力学模型Key words
nano-calcium phosphate/size effect/fluorescent labeling/tissue distribution/physiologically based pharmacokinetic model分类
化学化工引用本文复制引用
汤新丽,丁自友,陈俊锐,赵刚,韩颖超..基于稀土铕离子荧光标记的磷酸钙纳米材料体内分布与代谢研究[J].无机材料学报,2025,40(7):754-764,中插3-中插10,19.基金项目
国家自然科学基金(51672206) （51672206）
材料复合新技术国家重点实验室开放基金(2023-KF-9)National Natural Science Foundation of China(51672206) （2023-KF-9）
State Key Laboratory of Advanced Technology for Materials Synthesis and Processing(2023-KF-9) （2023-KF-9）
