Phosphatidylserine and/or Sialic Acid Modified Liposomes Increase Uptake by Tumor-associated Macrophages and Enhance the Anti-tumor Effect.
AAPS PharmSciTech
; 25(5): 125, 2024 Jun 04.
Article
em En
| MEDLINE
| ID: mdl-38834759
ABSTRACT
DOX liposomes have better therapeutic effects and lower toxic side effects. The targeting ability of liposomes is one of the key factors affecting the therapeutic effect of DOX liposomes. This study developed two types of targeted liposomes. Sialic acid (SA)-modified liposomes were designed to target the highly expressed Siglec-1 receptor on tumor-associated macrophages surface. Phosphatidylserine (PS)-modified liposomes were designed to promote phagocytosis by monocyte-derived macrophages through PS apoptotic signaling. In order to assess and compare the therapeutic potential of different targeted pathways in the context of anti-tumor treatment, we compared four phosphatidylserine membrane materials (DOPS, DSPS, DPPS and DMPS) and found that liposomes prepared using DOPS as material could significantly improve the uptake ability of RAW264.7 cells for DOX liposomes. On this basis, normal DOX liposomes (CL-DOX) and SA-modified DOX liposomes (SAL-DOX), PS-modified DOX liposomes (PS-CL-DOX), SA and PS co-modified DOX liposomes (PS-SAL-DOX) were prepared. The anti-tumor cells function of each liposome on S180 and RAW264.7 in vitro was investigated, and it was found that SA on the surface of liposomes can increase the inhibitory effect. In vivo efficacy results exhibited that SAL-DOX and PS-CL-DOX were superior to other groups in terms of ability to inhibit tumor growth and tumor inhibition index, among which SAL-DOX had the best anti-tumor effect. Moreover, SAL-DOX group mice had high expression of IFN-γ as well as IL-12 factors, which could significantly inhibit mice tumor growth, improve the immune microenvironment of the tumor site, and have excellent targeted delivery potential.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfatidilserinas
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Doxorrubicina
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Ácido N-Acetilneuramínico
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Macrófagos Associados a Tumor
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Lipossomos
Limite:
Animals
Idioma:
En
Revista:
AAPS PharmSciTech
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article