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Publications

Journal Article Epublish

PubMed: 40697323 DOI: 10.1016/j.mtbio.2025.102077

Neutrophil/monocyte-targeted dual-ligands modified liposomes delivering puerarin for ischemia stroke treatment.

Mater Today Bio 33:102077

Authors: Chengli Ling, Linglong Chen, Jianming Liang, Xiaofang Li, Hua Wei, Cuiyun Yu, Jianxin Wang

Affiliations

  • Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 201203, PR China. Hunan Province Hospital of Integrated Traditional Chinese and Western Medicine (Affiliated Hospital of Hunan Academy of Chinese Medicine), Hunan Academy of Chinese Medicine, Changsha, 410006, PR China.
  • Hunan Province Hospital of Integrated Traditional Chinese and Western Medicine (Affiliated Hospital of Hunan Academy of Chinese Medicine), Hunan Academy of Chinese Medicine, Changsha, 410006, PR China.
  • Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China.
  • Chengdu University of Chinese Medicine, Chengdu, 611137, PR China.
  • Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study & School of Pharmaceutical Science, Hengyang Medical School, University of South China, 28 W Changsheng Road, Hengyang, 421001, PR China.
  • Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 201203, PR China.

Abstract

Extremely low actual biological effect of insoluble small molecule drugs in ischemia region is a pain point and aporia in Ischemia Stroke (IS) therapy, Although there are studies on single, double-ligands modified liposomes or biomimetic exogenous carriers for directly targeting IS so far, but they often have off-target effects due to they were swallowed, degraded directly (instability) and sabotaged without the help of endogenous cell in the systemic circulation. DSPE-PEG 3400-PGP (PGP) and DSPE-PEG 3400-cRGD (cRGD) were synthesized via michael addition reaction of maleimide (-Mal) with sulfhydryl (-SH), succinimidyl ester (-NHS) with active primary amine group (-NH 2) respectively. The cRGD and PGP were modified on liposomes by thin film hydration method. Optimal modified ratio of cRGD and PGP were achieved by cellular uptake of HL-60 cells and THP-1 cells in vitro. The precise targeting effects of cRGD/PGP-Lips were examined in a nude MCAO model by an in a vivo imaging system. Puerarin (Pue) was cleverly encapsulated using a calcium acetate gradient to construct cRGD/PGP-Pue-Lips, and its therapeutic efficiency were assessed by rat MCAO model of IS. Optimal modification ratio for both cRGD and PGP were 3 %. The cRGD/PGP-Lips had significant synergetic targeting efficiency in vitro and in vivo, and the encapsulation efficiency of Pue were greater than 80 % through calcium acetate gradient. The cRGD/PGP-Pue-Lips could effectively penetrate BBB and enhance Pue retention on the brain ischemia region in vivo, resulting in a nearly two-fold reduction significantly in cerebral infarction area and edema in rats. In addition, cRGD/PGP-Pue-Lips didn't cause systemic toxicity in major organ tissues. Precise dual-ligands modified nanocarrier targeting endogenous cells is highly competitive as a novel anti-stroke and perspective for treatment of IS.

MeSH

Cells, Amines, Monocytes, Stroke, Liposomes, Acetates, Neutrophils, Calcium, Therapeutics, Ligands, Ischemia