The effects of stiffness on the specificity and avidity of antibody-coated microcapsules with target cells are strongly shape dependent

Liu, Rui1; Zhang, Zhe2; Liu, Lingrong1; Li, Xuemin1; Duan, Ruiping1; Ren, Ying1; Du, Bo1; Zhang, Qiqing1,3,4; Zhou, Zhimin1

2024-02-01

10.1016/j.colsurfb.2024.113752

COLLOIDS AND SURFACES B-BIOINTERFACES   影响因子和分区

0927-7765

1873-4367

Antibody modification is a common method for endowing drug carriers with the ability to target specific cells. Recent studies suggest that the efficacy of these antibody-modified drug carriers is closely related to their physicochemical properties, such as size, shape, stiffness, charge, and surface chemistry. In this study, we functionalized microcapsules with antibodies to investigate the combined effect of shape and stiffness on their targeting ability. We synthesized hollow microcapsules, both spherical and rod-shaped, with adjustable stiffness using calcium carbonate particles as templates and silk fibroin (SF) as the shell material. These microcapsules were then functionalized with trastuzumab (TTZ) to enhance targeting capabilities. Our analysis revealed that increasing stiffness significantly improved the specificity and avidity of TTZ-coated rod-shaped microcapsules, but not spherical ones, indicating a strong shape-dependent influence of stiffness on these properties. Additionally, we explored the mechanisms of endocytosis using various inhibitors and found that both macropinocytosis and clathrin played critical roles in the cellular uptake of microcapsules. Furthermore, we loaded microcapsules with doxorubicin (DOX) to evaluate their anti-tumor efficacy. The stiffest TTZ-coated, DOX-loaded rod-shaped microcapsules demonstrated the most potent anti-tumor effects on BT-474 cells and the highest uptake in BT-474 3D spheroids. This research contributes to the development of more effective microcapsulebased target delivery systems and the realization of the full potential of microcapsule drug delivery systems.

Cellular targeting Stiffness Shape Drug carriers Microcapsules

SCI ; EI

英语

通讯

National Natural Science Foundation of China["82204461","81501578","81972043"] ; National Key Basic Research and Development Projects[2017YFC1103601] ; Tianjin Natural Science Foundation[J230006] ; CAMS Innovation Fund for Medical Sciences[2021-I2M-1-052]

Biophysics ; Chemistry ; Materials Science

Biophysics ; Chemistry, Physical ; Materials Science, Biomaterials

WOS:001156439300001

ELSEVIER

BIOLOGY & BIOCHEMISTRY

Web of Science

1.Chinese Acad Med Sci & Peking Union Med Coll, Inst Biomed Engn, Biomed Barriers Res Ctr, Tianjin Key Lab Biomed Mat, Tianjin 300192, Peoples R China
2.Tianjin Med Univ, Sch Pharmaceut Sci, Tianjin Key Lab Technol Enabling Dev Clin Therapeu, Key Lab Immune Microenvironm & Dis Minist Educ, Tianjin 300070, Peoples R China
3.Fujian Bote Biotechnol Co Ltd, Fuzhou 350013, Fujian, Peoples R China
4.Southern Univ Sci & Technol, Jinan Univ,Inst Biomed Engn, Clin Med Coll 2, Shenzhen Peoples Hosp,Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China

Liu, Rui,Zhang, Zhe,Liu, Lingrong,et al. The effects of stiffness on the specificity and avidity of antibody-coated microcapsules with target cells are strongly shape dependent[J]. COLLOIDS AND SURFACES B-BIOINTERFACES,2024,234.

Liu, Rui.,Zhang, Zhe.,Liu, Lingrong.,Li, Xuemin.,Duan, Ruiping.,...&Zhou, Zhimin.(2024).The effects of stiffness on the specificity and avidity of antibody-coated microcapsules with target cells are strongly shape dependent.COLLOIDS AND SURFACES B-BIOINTERFACES,234.

Liu, Rui,et al."The effects of stiffness on the specificity and avidity of antibody-coated microcapsules with target cells are strongly shape dependent".COLLOIDS AND SURFACES B-BIOINTERFACES 234(2024).