Biodegradable Microembolics with Nanografted Polyanions Enable High-Efficiency Drug Loading and Sustained Deep-Tumor Drug Penetration for Locoregional Chemoembolization Treatment

Ma, Yutao1,2; Li, Zhihua1; Luo, Yucheng1; Chen, Yao1; Ma, Le1; Liu, Xiaoya1; Xiao, Jingyu1; Huang, Man1; Li, Yingnan1; Jiang, Hongliang1; Wang, Meijuan1; Wang, Xiaoqian1; Li, Jiangtao3; Kong, Jian4; Shi, Peng2,5; Yu, Hanry6,7,8; Jiang, Xingyu1; Guo, Qiongyu1

2024-07-01

10.1021/acsnano.4c00047

ACS NANO   影响因子和分区

1936-0851

1936-086X

Transarterial chemoembolization (TACE), the mainstay treatment of unresectable primary liver cancer that primarily employs nondegradable drug-loaded embolic agents to achieve synergistic vascular embolization and locoregional chemotherapy effects, suffers from an inferior drug burst behavior lacking long-term drug release controllability that severely limits the TACE efficacy. Here we developed gelatin-based drug-eluting microembolics grafted with nanosized poly(acrylic acid) serving as a biodegradable ion-exchange platform that leverages a counterion condensation effect to achieve high-efficiency electrostatic drug loading with electropositive drugs such as doxorubicin (i.e., drug loading capacity >34 mg/mL, encapsulation efficiency >98%, and loading time <10 min) and an enzymatic surface-erosion degradation pattern (similar to 2 months) to offer sustained locoregional pharmacokinetics with long-lasting deep-tumor retention capability for TACE treatment. The microembolics demonstrated facile microcatheter deliverability in a healthy porcine liver embolization model, superior tumor-killing capacity in a rabbit VX2 liver cancer embolization model, and stabilized extravascular drug penetration depth (>3 mm for 3 months) in a rabbit ear embolization model. Importantly, the microembolics finally exhibited vessel remodeling-induced permanent embolization with minimal inflammation responses after complete degradation. Such a biodegradable ion-exchange drug carrier provides an effective and versatile strategy for enhancing long-term therapeutic responses of various local chemotherapy treatments.

liver cancer transarterial chemoembolization biodegradable drug-elutingbeads deep-tumor drug penetration counterion condensation

SCI ; EI

英语

第一 ; 通讯

National Natural Science Foundation of China[2020YFA0908900] ; National Key R&D Program of China[81971764] ; National Natural Science Foundation of China[2019ZT08Y191] ; Guangdong Research Fund[KQTD20200820113012029] ; Shenzhen Science and Technology Innovation Commission[JCYJ20200109141638004] ; Innovation Committee of Shenzhen Municipality[2022B1212010003] ; Guangdong Provincial Key Laboratory of Advanced Biomaterials[ZDSYS20200811144003009]

Chemistry ; Science & Technology - Other Topics ; Materials Science

Chemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:001260656400001

AMER CHEMICAL SOC

Web of Science

1.Southern Univ Sci & Technol, Dept Biomed Engn, Shenzhen Key Lab Smart Healthcare Engn, Guangdong Prov Key Lab Adv Biomat, Shenzhen 518055, Guangdong, Peoples R China
2.City Univ Hong Kong, Dept Biomed Engn, Kowloon, Hong Kong 999077, Peoples R China
3.Zhejiang Univ, Affiliated Hosp 2, Sch Med, Dept Surg, Hangzhou 310009, Zhejiang, Peoples R China
4.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Intervent Radiol,Affiliated Hosp 1,Southern U, Shenzhen 518020, Guangdong, Peoples R China
5.City Univ Hong Kong, Shenzhen Res Inst, Shenzhen 518057, Guangdong, Peoples R China
6.Natl Univ Singapore, Mechanobiol Inst, Singapore 117411, Singapore
7.Yong Loo Lin Sch Med, Inst Digital Med WisDM, Dept Physiol, Singapore 117593, Singapore
8.Singapore MIT Alliance Res & Technol, Singapore 138602, Singapore

Ma, Yutao,Li, Zhihua,Luo, Yucheng,et al. Biodegradable Microembolics with Nanografted Polyanions Enable High-Efficiency Drug Loading and Sustained Deep-Tumor Drug Penetration for Locoregional Chemoembolization Treatment[J]. ACS NANO,2024.

Ma, Yutao.,Li, Zhihua.,Luo, Yucheng.,Chen, Yao.,Ma, Le.,...&Guo, Qiongyu.(2024).Biodegradable Microembolics with Nanografted Polyanions Enable High-Efficiency Drug Loading and Sustained Deep-Tumor Drug Penetration for Locoregional Chemoembolization Treatment.ACS NANO.

Ma, Yutao,et al."Biodegradable Microembolics with Nanografted Polyanions Enable High-Efficiency Drug Loading and Sustained Deep-Tumor Drug Penetration for Locoregional Chemoembolization Treatment".ACS NANO (2024).