Lipid Envelope-Type Nanoparticle Incorporating a Multifunctional Peptide for Systemic siRNA Delivery to the Pulmonary Endothelium
Kenji Kusumoto
Hidetaka Akita
Taichi Ishitsuka
Yu Matsumoto
Takahiro Nomoto
Ryo Furukawa
Ayman El-Sayed
Hiroto Hatakeyama
Kazuaki Kajimoto
Yuma Yamada
Kazunori Kataoka
Hideyoshi Harashima
10.1021/nn401317t.s004
https://acs.figshare.com/articles/media/Lipid_Envelope_Type_Nanoparticle_Incorporating_a_Multifunctional_Peptide_for_Systemic_siRNA_Delivery_to_the_Pulmonary_Endothelium/2373847
A system that permits the delivery of cargoes to the lung endothelium would be extraordinarily useful in terms of curing a wide variety of lung-related diseases. This study describes the development of a multifunctional envelope-type nanodevice (MEND) that targets the lung endothelium, delivers its encapsulated siRNA to the cytoplasm, and eradicates lung metastasis. The key to the success can be attributed to the presence of a surface-modified GALA peptide that has dual functions: targeting the sialic acid-terminated sugar chains on the pulmonary endothelium and subsequently delivering the encapsulated cargoes to the cytosol <i>via</i> endosomal membrane fusion, analogous to the influenza virus. The active targeting of MENDs without the formation of large aggregates was verified by intravital real-time confocal laser scanning microscopy in living lung tissue. The GALA-modified MEND is a promising carrier that opens a new generation of therapeutic approaches for satisfying unmet medical needs in curing lung diseases.
2013-09-24 00:00:00
encapsulated
Systemic siRNA Delivery
confocal laser scanning microscopy
eradicates lung metastasis
endosomal membrane fusion
cargo
GALA
lung endothelium
MEND
Pulmonary EndotheliumA system