当前位置： SCI文献检索 > AAPS PHARMSCITECH期刊下所有文献 > PD-1 siRNA-Encapsulated Solid Lipid Nanoparticles Downregulate PD-1 Expression by Macrophages and Inhibit Tumor Growth : PD-1 siRNA-Encapsulated Solid Lipid Nanoparticles.

PD-1 siRNA-Encapsulated Solid Lipid Nanoparticles Downregulate PD-1 Expression by Macrophages and Inhibit Tumor Growth : PD-1 siRNA-Encapsulated Solid Lipid Nanoparticles.

Abstract：

:The present study was designed to test the hypothesis that programmed cell death-1 (PD-1) siRNA can downregulate PD-1 expression in macrophages in culture and in tumor tissues in mice and inhibit tumor growth in a mouse model. PD-1 siRNA was encapsulated in solid lipid nanoparticles (SLNs), and the physical properties of the resultant SLNs were characterized. The ability of the PD-1 siRNA-SLNs to downregulate PD-1 expression was confirmed in J774A.1 macrophages in culture and in tumor tissues in mice. Moreover, the antitumor activity of the PD-1 siRNA-SLNs was evaluated in a mouse model. The PD-1 siRNA-SLNs were roughly spherical, and their particle size, polydispersity index, and zeta potential were 141 ± 5 nm, 0.17 ± 0.02, and 20.7 ± 4.7 mV, respectively, with an siRNA entrapment efficiency of 98.9%. The burst release of the PD-1 siRNA from the SLNs was minimal. The PD-1 siRNA-SLNs downregulated PD-1 expression on J774A.1 macrophage cell surface as well as in macrophages in B16-F10 tumors pre-established in mice. In mice with pre-established B16-F10 tumors, the PD-1 siRNA-SLNs significantly inhibited the tumor growth, as compared with siRNA-SLNs prepared with non-functional, negative control siRNA. In conclusion, the PD-1 siRNA-SLNs inhibited tumor growth, likely related to their ability to downregulate PD-1 expression by tumor-associated macrophage (TAMs).

journal_name

AAPS PharmSciTech

journal_title

AAPS PharmSciTech

authors

Hanafy MS,Hufnagel S,Trementozzi AN,Sakran W,Stachowiak JC,Koleng JJ,Cui Z

doi

10.1208/s12249-021-01933-y

subject

Has Abstract

pub_date

2021-01-31 00:00:00

pages

60

issue

2

issn

1530-9932

pii

10.1208/s12249-021-01933-y

journal_volume

22

pub_type

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