Megakaryocyte membrane‐wrapped nanoparticles for targeted cargo delivery to hematopoietic stem and progenitor cells

Hematopoietic stem and progenitor cells (HSPCs) are desirable targets for gene therapy but are notoriously difficult to target and transfect. Existing viral vector‐based delivery methods are not effective in HSPCs due to their cytotoxicity, limited HSPC uptake and lack of target specificity (tropism...

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Published inBioengineering & translational medicine Vol. 8; no. 3; pp. e10456 - n/a
Main Authors Das, Samik, Harris, Jenna C., Winter, Erica J., Kao, Chen‐Yuan, Day, Emily S., Papoutsakis, Eleftherios Terry
Format Journal Article
LanguageEnglish
Published Hoboken, USA John Wiley & Sons, Inc 01.05.2023
Wiley
Subjects
Acids
Biocompatibility
biomimetic
Blood
Bone marrow
Cargo
Cells (biology)
Controlled release
endocytosis
Flow cytometry
gene regulation
Gene therapy
Glycolic acid
hematopoietic stem cells
Membranes
membrane‐wrapped
MicroRNAs
Nanoparticles
Polyethylene glycol
Ribonucleic acid
RNA
targeted delivery
Toxicity
Transmission electron microscopy
Tropism
endocytosis
targeted delivery
hematopoietic stem cells
gene regulation
membrane‐wrapped
biomimetic
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Summary:Hematopoietic stem and progenitor cells (HSPCs) are desirable targets for gene therapy but are notoriously difficult to target and transfect. Existing viral vector‐based delivery methods are not effective in HSPCs due to their cytotoxicity, limited HSPC uptake and lack of target specificity (tropism). Poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles (NPs) are attractive, nontoxic carriers that can encapsulate various cargo and enable its controlled release. To engineer PLGA NP tropism for HSPCs, megakaryocyte (Mk) membranes, which possess HSPC‐targeting moieties, were extracted and wrapped around PLGA NPs, producing MkNPs. In vitro, fluorophore‐labeled MkNPs are internalized by HSPCs within 24 h and were selectively taken up by HSPCs versus other physiologically related cell types. Using membranes from megakaryoblastic CHRF‐288 cells containing the same HSPC‐targeting moieties as Mks, CHRF‐wrapped NPs (CHNPs) loaded with small interfering RNA facilitated efficient RNA interference upon delivery to HSPCs in vitro. HSPC targeting was conserved in vivo, as poly(ethylene glycol)–PLGA NPs wrapped in CHRF membranes specifically targeted and were taken up by murine bone marrow HSPCs following intravenous administration. These findings suggest that MkNPs and CHNPs are effective and promising vehicles for targeted cargo delivery to HSPCs.
Bibliography:Samik Das and Jenna C. Harris contributed equally to this work.
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ISSN:2380-6761
2380-6761
DOI:10.1002/btm2.10456