Development of flexible nanocarriers for siRNA delivery into tumor tissue

Jung, Ho-Youl; Shimatani, Yuri; Hasan, Mahadi; Uno, Kohei; Hama, Susumu; Kogure, Kentaro

doi:10.1016/j.ijpharm.2016.11.042

Cited by 4 publications

(4 citation statements)

References 20 publications

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“…For example, retroviral infection allowed the sustained expression of GFP in more than 90% of cells from organoid fragments that were removed from Matrigel ( 12 ). In other studies, researchers managed to achieve high transfection efficiencies using polyplex nanomicelles ( 37 ), flexible nanocarriers ( 38 ) or polyamine nanoparticles ( 39 ) on MCTS. However, these studies were performed on incomplete 3D models, cell aggregates such as MCTS or dissociated organoids devoid of any exogenous ECM ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Direct transfection of clonal organoids in Matrigel microbeads: a promising approach toward organoid-based genetic screens

Laperrousaz

Porte

Gerbaud

et al. 2018

Nucleic Acids Research

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Organoid cultures in 3D matrices are relevant models to mimic the complex in vivo environment that supports cell physiological and pathological behaviors. For instance, 3D epithelial organoids recapitulate numerous features of glandular tissues including the development of fully differentiated acini that maintain apico-basal polarity with hollow lumen. Effective genetic engineering in organoids would bring new insights in organogenesis and carcinogenesis. However, direct 3D transfection on already formed organoids remains challenging. One limitation is that organoids are embedded in extracellular matrix and grow into compact structures that hinder transfection using traditional techniques. To address this issue, we developed an innovative approach for transgene expression in 3D organoids by combining single-cell encapsulation in Matrigel microbeads using a microfluidic device and electroporation. We demonstrate that direct electroporation of encapsulated organoids reaches up to 80% of transfection efficiency. Using this technique and a morphological read-out that recapitulate the different stages of tumor development, we further validate the role of p63 and PTEN as key genes in acinar development in breast and prostate tissues. We believe that the combination of controlled organoid generation and efficient 3D transfection developed here opens new perspectives for flow-based high-throughput genetic screening and functional genomic applications.

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Section: Discussionmentioning

confidence: 99%

Direct transfection of clonal organoids in Matrigel microbeads: a promising approach toward organoid-based genetic screens

Laperrousaz

Porte

Gerbaud

et al. 2018

Nucleic Acids Research

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“…As well known, the physicochemical characteristics (size [ 155 ], surface charge [ 156 ], particle shape and rigidity/flexibility [ 157 ] of structures) play critical roles in tissue penetration and accumulation capability. Generally, small-size NPs have good tissues ( e.g.…”

Section: Synthetic Non-viral Vectors For Rna Deliverymentioning

confidence: 99%

“…In addition, the rigidity/flexibility of NPs is also a key factor for tissues permeability and accumulation. The rigid structures of the nanocarriers are considered to prevent penetration into deeper regions within tumor tissue [ 157 ]. While a flexible nanocarrier can be deformed during the paracellular transport, facilitating the intratumoral accumulation.…”

Section: Synthetic Non-viral Vectors For Rna Deliverymentioning

confidence: 99%

“…While a flexible nanocarrier can be deformed during the paracellular transport, facilitating the intratumoral accumulation. For example, a siRNA-loaded non-cationic soft polyphenol nanocapsule called Nanosac was developed by sequential coating of MSN with siRNA and polydopamine, followed by removal of the sacrificial MSN core to produce a hollow structure [ 157 ]. The results of intravital confocal microscopy showed that the mean fluorescence intensity (MFI) of soft Nanosac in the tumor spheroid was 2-fold higher than that of hard NPs (MSNa-cy5/pD), indicating that the soft NPs with flexible structure could improve penetration and accumulation of RNAs at tumors compared to hard counterpart.…”

Section: Synthetic Non-viral Vectors For Rna Deliverymentioning

confidence: 99%

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Non-viral vectors for RNA delivery

Yan

Liu

et al. 2022

Journal of Controlled Release

152

100

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RNA-based therapy is a promising and potential strategy for disease treatment by introducing exogenous nucleic acids such as messenger RNA (mRNA), small interfering RNA (siRNA), microRNA (miRNA) or antisense oligonucleotides (ASO) to modulate gene expression in specific cells. It is exciting that mRNA encoding the spike protein of COVID-19 (coronavirus disease 2019) delivered by lipid nanoparticles (LNPs) exhibits the efficient protection of lungs infection against the virus. In this review, we introduce the biological barriers to RNA delivery in vivo and discuss recent advances in non-viral delivery systems, such as lipid-based nanoparticles, polymeric nanoparticles, N -acetylgalactosamine (GalNAc)-siRNA conjugate, and biomimetic nanovectors, which can protect RNAs against degradation by ribonucleases, accumulate in specific tissue, facilitate cell internalization, and allow for the controlled release of the encapsulated therapeutics.

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Quantifying how drug-polymer interaction and volume phase transition modulate the drug release kinetics from core-shell microgels

Lim

Irwan

et al. 2022

International Journal of Pharmaceutics

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Development of flexible nanocarriers for siRNA delivery into tumor tissue

Cited by 4 publications

References 20 publications

Direct transfection of clonal organoids in Matrigel microbeads: a promising approach toward organoid-based genetic screens

Direct transfection of clonal organoids in Matrigel microbeads: a promising approach toward organoid-based genetic screens

Non-viral vectors for RNA delivery

Quantifying how drug-polymer interaction and volume phase transition modulate the drug release kinetics from core-shell microgels

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