Lipid-based siRNA Nanodelivery Systems: A Learning Process for Improving Transfer from Concepts to Clinical Applications

Pérez, Sebastián E.; Carlucci, Adriana

doi:10.2174/1574884713666180829143054

“…Compared to other nano-sized delivery systems, such as lipid, polymers, gold, and silica material [27][28][29][30][31][32] , exosomes are living-cell derived, highly biocompatible nano-carriers with intrinsic payload, and exhibit much stronger flexibility in loading desired antigens for effective delivery 33 . Exosomes also eliminate allergenic responses without concerns of carrying virulent factors and avoid degradation or loss during delivery [34][35] .…”

Section: Introductionmentioning

confidence: 99%

Microfluidic on-demand engineering of exosomes towards cancer immunotherapy

Zhao

¹

,

McGill

²

,

Gamero-Kubota

³

et al. 2019

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“…Compared to other nano-sized delivery systems, such as lipid, polymers, gold, and silica material [27][28][29][30][31][32] , exosomes are living-cell derived, highly biocompatible nano-carriers with intrinsic payload, and exhibit much stronger flexibility in loading desired antigens for effective delivery 33 . Exosomes also eliminate allergenic responses without concerns of carrying virulent factors and avoid degradation or loss during delivery [34][35] .…”

Section: Introductionmentioning

confidence: 99%

Microfluidic On-demand Engineering of Exosomes towards Cancer Immunotherapy

Zhao

¹

,

McGill

²

,

He

³

2018

Preprint

1

0

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Extracellular Vesicles (EVs), particularly exosomes (30-150 nm), are an emerging delivery system in mediating cellular communications, which have been observed for priming immune responses by presenting parent cell signaling proteins or tumor antigens to immune cells. Therefore, preparation of antigenic exosomes that can play therapeutic roles, particularly in cancer immunotherapy, is emerging. However, standard benchtop methods (e.g., ultracentrifugation and filtration) lack the ability to purify antigenic exosomes specifically among other microvesicle subtypes, due to the non-selective and timeconsuming (>10 h) isolation protocols. Exosome engineering approaches, such as the transfection of parent cells, also suffer from poor yield, low purity, and time-consuming operations. In this paper, we introduce a streamlined microfluidic cell culture platform for integration of harvesting, antigenic modification, and photo-release of surface engineered exosomes in one workflow, which enables the production of intact, MHC peptide surface engineered exosomes for cytolysis activation.The PDMS microfluidic cell culture chip is simply cast from a 3D-printed mold. The proof-of-concept study demonstrated the enhanced ability of harvested exosomes in antigen presentation and T cell activation, by decorating melanoma tumor peptides on the exosome surface (e.g., gp-100, MART-1, MAGE-A3). Such surface engineered antigenic exosomes were harvested in real-time from the on-chip culture of leukocytes isolated from human blood, leading to much faster cellular uptake. The activation of gp100-specific CD8 T cells which were purified from the spleen of 2 Pmel1 transgenic mice was evaluated using surface engineered exosomes prepared from muring antigen presenting cells. Antigen-specific CD8 T cell proliferation was significantly induced by the engineered exosomes compared to native, non-engineered exosomes. This microfluidic platform serves as an automated and highly integrated cell culture device for rapid, and real-time production of therapeutic exosomes that could advance cancer immunotherapy.

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