Possible contribution of sialic acid to the enhanced tumor targeting efficiency of nanoparticles engineered with doxorubicin

Song Yi Lee,Suyeong Nam,Chaerim Hwang,Da In Jeong,Ja Seong Koo,Mingyu Yang,Sungyun Kim,Hyun-Jong Cho,Jihye Park

doi:10.1038/s41598-020-76778-9

Song Yi Lee, Suyeong Nam + Show 7 more

Open Access

https://doi.org/10.1038/s41598-020-76778-9

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Journal: Scientific Reports	Publication Date: Nov 12, 2020
Citations: 9	License type: open-access

Affiliation: Kangwon National University

Abstract

Doxorubicin (DOX)-engineered poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) including phloretin (PHL) were designed and the feasible contribution of sialic acid (SA) to the improved tumor targeting and penetration capabilities was elucidated in lung adenocarcinoma models. DOX has been clinically used as liposomal formulations after its introduction to the inner side of vehicles, however DOX is anchored in the outer surface of PLGA NPs for improved tumor penetration by interactions with SA in this study. DOX (positively charged at physiological pH) was adsorbed onto the negatively charged PLGA NPs via electrostatic interactions and consequent binding of SA (negatively charged at physiological pH) to DOX located in NPs was also elucidated. DOX layer in DOX@PLGA NPs rendered improved endocytosis and partial contribution of SA (expressed in cancer cells) to that endocytosis was demonstrated. DOX@PLGA/PHL NPs provided enhanced antiproliferation potentials in A549 cells rather than single agent (DOX or PHL)-installed NPs. In addition, DOX-SA interactions seemed to play critical roles in tumor infiltration and accumulation of DOX@PLGA NPs in A549 tumor-xenografted mouse model. All these findings support the novel use of DOX which is used for the surface engineering of NPs for improved tumor targeting and penetration.

Highlights

Doxorubicin (DOX)-engineered poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) including phloretin (PHL) were designed and the feasible contribution of sialic acid (SA) to the improved tumor targeting and penetration capabilities was elucidated in lung adenocarcinoma models
PHL was loaded to PLGA NPs as an anticancer agent and DOX was coated onto the outer layer of PLGA/PHL NPs aiming at elevated cellular accumulation, tumor infiltration, and antiproliferation in this study (Fig. 1)
DOX was introduced to the outer surface of PLGA/PHL NPs for improved tumor targeting and penetration probably based on DOX-SA interactions in this study

Summary

Introduction

Doxorubicin (DOX)-engineered poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) including phloretin (PHL) were designed and the feasible contribution of sialic acid (SA) to the improved tumor targeting and penetration capabilities was elucidated in lung adenocarcinoma models. Nature of PLGA, hydrophilic or hydrophobic drug cargos can be coated to the outer layer of PLGA NPs or loaded to the internal space of PLGA NPs3 In this investigation, doxorubicin HCl (DOX)-engineered PLGA NPs (DOX@PLGA NPs) containing phloretin (PHL) were designed for the enhancement of tumor targeting and penetrating potentials. Contrary to the incorporated DOX molecules in the liposomal structures (i.e., Doxil) which are clinically available, externally attached DOX onto NPs is expected to provide tumor targeting and penetrating capabilities as well as chemotherapeutic efficacies in tumor tissues. Physicochemical and biological functions of DOX-engineered PLGA NPs including PHL will be systemically assessed in this study

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