Abstract
Protein corona presents a major obstacle to bench-to-bedside translation of targeted drug delivery systems, severely affecting targeting yields and directing unfavorable biodistribution. Corona-mediated targeting provides a new impetus for specific drug delivery by precisely manipulating interaction modes of functional plasma proteins on nano-surface. Here bio-inspired liposomes (SP-sLip) were developed by modifying liposomal surface with a short nontoxic peptide derived from Aβ1-42 that specifically interacts with the lipid-binding domain of exchangeable apolipoproteins. SP-sLip absorb plasma apolipoproteins A1, E and J, consequently exposing receptor-binding domain of apolipoproteins to achieve brain-targeted delivery. Doxorubicin loaded SP-sLip (SP-sLip/DOX) show significant enhancement of brain distribution and anti-brain cancer effect in comparison to doxorubicin loaded plain liposomes. SP-sLip preserve functions of the absorbed human plasma ApoE, and the corona-mediated targeting strategy works in SP modified PLGA nanoparticles. The present study may pave a new avenue to facilitate clinical translation of targeted drug delivery systems.
Highlights
Protein corona presents a major obstacle to bench-to-bedside translation of targeted drug delivery systems, severely affecting targeting yields and directing unfavorable biodistribution
Protein corona presents a major obstacle to the bench-to-bedside translation of targeted drug delivery systems (TDDS)
Exchangeable apolipoproteins that can direct the transport of lipids through lymphatic and circulatory systems have been found in protein coronas formed on the surface of a variety of drug delivery systems[15,16,17]
Summary
Protein corona presents a major obstacle to bench-to-bedside translation of targeted drug delivery systems, severely affecting targeting yields and directing unfavorable biodistribution. Corona-mediated targeting provides a new impetus for specific drug delivery by precisely manipulating interaction modes of functional plasma proteins on nano-surface. Exchangeable apolipoproteins (such as ApoA, C, and E) that can direct the transport of lipids through lymphatic and circulatory systems have been found in protein coronas formed on the surface of a variety of drug delivery systems[15,16,17] Some of those exchangeable apolipoproteins (ApoA1 and ApoE) can cross the blood-brain barrier (BBB) via receptor-mediated transcytosis[18,19,20,21]; it is rarely reported that plain drug delivery systems (without modification of brain-targeting ligands) penetrate the BBB after absorption of such apolipoproteins in blood. After entry into blood stream, SP-sLip are anticipated to associate brain targeting apolipoproteins (i.e., ApoE, ApoJ, and ApoA1) via the interaction between SP and the lipid-binding domain of apolipoproteins Their receptor-binding domains are exposed on the liposomal surface for multiple receptors recognition (LRP1/ApoE, LRP2/ApoJ, and SRB1/ApoA1) and brain transport via LRP1/LRP2/SR-B1 mediated transcytosis. The brain targeting efficiency and anti-brain cancer effect of doxorubicin-loaded SP-sLip (SP-sLip/DOX) are studied and the application of this novel targeting strategy in other nanomedicines (such as PLGA nanoparticles) is investigated
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