Brain-targeted drug delivery by manipulating protein corona functions

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 Aβ 1-42 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.

Recent Advances in Understanding the Protein Corona of Nanoparticles and in the Formulation of “Stealthy” Nanomaterials

“…Similarly, the impact of NP-to-protein ratio in a complex medium has been assessed by a recent study by Zhang et al (2019). NPs coated with differently charged surfactants to modulate their zeta potential (ζ) had different PC features based on their concentration in solution (range 125-1,000 µg/ml) after incubation with 5% FBS at different time points over a period of 60 min.…”

“…The archetype of such hard-to-tackle obstacle is represented by the BBB, which prevents brain targeting using traditional drugs due to reduced diffusion and active extrusion of active molecules from the CNS. This challenge was undertaken by Zhang et al (2019) in a recent work. In this study, novel biomimetic liposomes, functionalized with a peptide derived from Aβ amyloid (SP) and loaded with DOXO (SP-Lipo-DOXO) for the treatment of glioblastoma, were tested.…”

Engineering Versatile Nanoparticles for Near‐Infrared Light‐Tunable Drug Release and Photothermal Degradation of Amyloid β

“…Without bEnd.3 cells monolayer, the transport percentage was calculated to be 57%, whereas the permeability of PDLC NPs across the BBB layer was 30%. The comparable transport efficiency of PDLC NPs across the BBB might be attributed to corona‐mediated brain targeting using a short peptide derived from Aβ protein . With NIR irradiation, the permeability was increased to 42%, which was ascribed to the local hyperthermia .…”

Recent Advances in Nanocarrier-Assisted Therapeutics Delivery Systems

“…In addition to using bioinspired nanomaterials to develop new nanocarriers, existing nanocarriers can also be modified in a bioinspired fashion. Zhang et al recently developed a liposomal nanocarrier with a modified surface that has a short nontoxic peptide derived from Aβ1-42 that specifically interacts with the lipid-binding domain of apolipoproteins [157]. These nanocarriers absorb plasma apolipoproteins A1, E, and J, resulting in the exposure of the receptor-binding domain of apolipoproteins to achieve brain-targeting drug delivery [157].…”