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Gold nanostars loaded erythrocyte ghost membrane as biomimetic nanotheranostic agent for homotypic targeting and hypoxic tumor treatment

Wrenit Gem Pearl,1 Rajakar Selvam,1 Artashes V. Karmenyan,1 Elena V. Perevedentseva,2 Shih-Che Hung,3 Hsin-Hou Chang,3 Chia-Liang Cheng,1*
1 Department of Physics, National Dong Hwa University, Hualien 97401, Taiwan
2 P. N. Lebedev Physics Institute of Russian Academy of Sciences, Moscow, 119991, Russia
3 Department of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien 97004, Taiwan

Abstract

Cancer has been one of the leading causes of death globally. Although nanomedicine have been made progress in alleviating cancer, certain types of tumor remain challenging to completely obliterate and becomes treatment resistance due to the severe hypoxic microenvironment. Herein, gold nanostars (AuNSts) loaded erythrocyte ghost cell membrane (AuNSt@ghost) were fabricated for homotypic targeting and the presence of residual hemoglobin in the erythrocyte ghosts acts as an oxygen carrier to relieve the hypoxia. AuNSts have been evidenced as a dual photo based photodynamic therapy (PDT) and photothermal therapy (PTT) abilities, generating reactive oxygen species (ROS) for PDT and inducing an incomparable light-to-heat conversion for ablating tumor environment under near infrared (NIR) laser irradiation. AuNSts with tunable optical properties in the NIR optical window gives a strong emission intensity at two-photon excitation. This property of AuNSts offers a great potential for bioimaging applications. Here, AuNSts with plasmon absorption peak around 800 nm wavelength was synthesized and loaded in erythrocyte ghosts. The intracellular localization of AuNSt@ghosts was visualized using two-photon FLIM. A strong emission of AuNSts at two-photon excitation was observed with estimated fluorescence lifetime of 0.5 ns. The enhanced antitumor effect of AuNSts were confirmed in 2D monolayer and 3D spheroid cultures under 808 nm laser irradiation. The obtained results demonstrate that AuNSt@ghost can work as an oxygen vehicle, offering an enhanced therapeutic effect. Therefore, AuNSt@ghost can be considered as a novel biomimetic agent for nanotheranostics applications.

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Speaker

Wrenit Gem Pearl Irudaya Raj
National Dong Hwa University
Taiwan

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