期刊
MOLECULAR PHARMACEUTICS
卷 16, 期 2, 页码 907-913出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.8b01216
关键词
blood-brain barrier; peptide ligand; immunocompatibility; glioblastoma; targeted drug delivery
资金
- National Natural Science Foundation of China [81673361, 81690263, 81803455, 81673370]
- Shanghai Education Commission Major Project [2017-01-07-00-07-E00052]
- Shanghai Natural Science Foundation [18ZR1404800]
- Shanghai Municipal Health Commission [2018BR04]
Peptide ligands have been exploited as versatile tools to facilitate targeted delivery of nanocarriers. However, the effects of peptide ligands on immunocompatibility and therapeutic efficacy of liposomes remain intricate. Here, a short and stable brain targeted peptide ligand D8 was modified on the surface of doxorubicin-loaded liposomes (D8-sLip/DOX), demonstrating prolonged blood circulation and lower liver distribution in comparison to the long and stable D-peptide ligand (CDX)-C-D-modified doxorubicin-loaded liposomes ((CDX)-C-D-sLip/DOX) by mitigating natural IgM absorption. Despite the improved pharmacokinetic profiles, D8-sLip/DOX exhibited comparable brain targeting capacity in ICR mice and antiglioblastoma efficacy to (CDX)-C-D-sLip/DOX in nude mice bearing intracranial glioblastoma. However, dramatic accumulation of (CDX)-C-D-sLip/DOX in liver (especially during the first 8 h after intravenous injection) resulted in pathological symptoms, including nuclei swelling, necrosis of liver cells, and inflammation. These results suggest that short peptide ligand-mediated brain-targeted drug delivery systems possessing enhanced immunocompatibility are promising to facilitate efficient brain transport with improved biosafety.
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