The photodynamic (PD) effect has been reported to be efficient for the opening of the blood-brain barrier (BBB), which provides a new informative platform for developing perspective strategies towards
brain disease therapy and drug delivery. However, this method is usually performed via
craniotomy due to high scattering of the turbid skull. In this work, we employed a newly-developed optical clearing skull window for investigating non-invasive PD-induced BBB opening to high weight molecules and 100-nm fluid-phase
liposomes containing
ganglioside GM1. The results demonstrated that the BBB permeability to the
Evans blue albumin complex is related to
laser doses. By in vivo two-photon imaging and ex vivo confocal imaging with specific markers of the BBB, we noticed PD-related extravasation of
rhodamine-dextran and
liposomes from the vessels into the brain parenchyma. The PD induced an increase in oxidative stress associated with mild
hypoxia and changes in the expression of tight junction (CLND-5 and ZO-1) and adherens junction (
VE-cadherin)
proteins, which might be one of the mechanisms underlying the PD-related BBB opening for
liposomes. Our experiments indicate that optical clearing skull window will be a promising tool for non-invasive PD-related BBB opening for high weight molecules and
liposomes that provides a novel useful tool for brain drug delivery and treatment of
brain diseases.