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Doxorubicin liposomes cell penetration enhancement and its potential drawbacks for the tumor targeting efficiency.

Abstract：

:The clinical efficacy of the PEGylated doxorubicin liposomes (PLD) is limited by low tumor accumulation and limited intra-tumoral disposition. Decoration with the cell penetration enhancers (CPEs) can increase the PLD permeability via the biological barriers, however at the expense of enhanced distribution to the non-target organs and tissues, and may interfere with their tumor accumulation and with the resulting anti-cancer effects. We investigated the effect of the surface CPE agent tetraArg-[G-1]-distearoyl glycerol (DAG-Arg4) on the systemic and intra-tumoral accumulation of PLD, using a 4 T1-Luc murine orthotopic model of breast cancer, using several analytical approaches. CPE-decorated liposomes undergo efficient in vitro endocytosis, and delivered doxorubicin to the cell nuclei. In vivo, they had lower tumor and spleen accumulation, similar liver accumulation, and higher lung accumulation, as compared to those of the PLD. Despite the lower tumor accumulation, CPE-decorated liposomes induced more prominent in vivo anti-cancer effects, as compared to the PLD, apparently ascribable to the higher intra-tumoral permeability mediated by the CPE surface residues. Overall, liposomes decoration with the CPE residues had mostly beneficial effects on their systemic and intra-tumoral disposition. The mechanisms of the CPE-mediated effects on the liposome disposition should be further assessed with additional experimental models using robust analytical methods with high spatial resolution.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Popilski H,Feinshtein V,Kleiman S,Mattarei A,Garofalo M,Salmaso S,Stepensky D

doi

10.1016/j.ijpharm.2020.120012

subject

Has Abstract

pub_date

2021-01-05 00:00:00

pages

120012

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(20)30997-2

journal_volume

592

pub_type

杂志文章

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