Passion fruit-like exosome-PMA/Au-BSA@Ce6 nanovehicles for real-time fluorescence imaging and enhanced targeted photodynamic therapy with deep penetration and superior retention behavior in tumor

Abstract

Exosomes (Exos) of approximately 30-150 nm in diameters are the promising vehicles for therapeutic drugs. However, several challenges still exist in clinical applications, such as unsatisfied yield of exosomes, complicated labeling procedure and low drug loading efficiency. In this work, the gram-scale amount of high-purity urinary exosomes can be obtained from gastric cancer patients by non-invasive method. Passion fruit-like Exo-PMA/Au-BSA@Ce6 nanovehicles were fabricated by considerable freshly-urinary Exos loaded efficiently with multi-functionalized PMA/Au-BSA@Ce6 nanoparticles via instant electroporation strategy. In this system, prepared Exo-PMA/Au-BSA@Ce6 nanovehicles could be internalized into cancer cells effectively, and could delay the endocytosis of macrophages and prolong blood circulation time owing to its membrane structure and antigens. Under 633 nm laser irradiation and acidic condition, the structures of nanovehicles would be collapsed and tremendous PMA/Au-BSA@Ce6 nanoparticles could be released inside cancer cells, produced considerable singlet oxygen, inhibiting growth of tumor cells. In vivo experiment of MGC-803 tumor-bearing nude mice showed that prepared Exo-PMA/Au-BSA@Ce6 nanovehicles could target tumor cells with deep penetration and superior retention performance in tumors. This work reports a reliable conjugation-free labeling strategy for tracking exosomes harvested from human urine. Moreover, the integration of multifunctional nanoparticles with urinary Exos paves a versatile road for the development of cancer-targeted photodynamic therapy.

Keywords: Fluorescence imaging; Nanovehicles; Photodynamic therapy; Ultra-small gold nanoparticles; Urinary exosome.