Megakaryocyte membrane‐wrapped nanoparticles for targeted cargo delivery to hematopoietic stem and progenitor cells
Abstract 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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-05-01
|
| Series: | Bioengineering & Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/btm2.10456 |
| _version_ | 1827946077545824256 |
|---|---|
| author | Samik Das Jenna C. Harris Erica J. Winter Chen‐Yuan Kao Emily S. Day Eleftherios Terry Papoutsakis |
| author_facet | Samik Das Jenna C. Harris Erica J. Winter Chen‐Yuan Kao Emily S. Day Eleftherios Terry Papoutsakis |
| author_sort | Samik Das |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-13T10:53:37Z |
| format | Article |
| id | doaj.art-aca1d621ab66431490d1c4b03729a9b3 |
| institution | Directory Open Access Journal |
| issn | 2380-6761 |
| language | English |
| last_indexed | 2024-03-13T10:53:37Z |
| publishDate | 2023-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioengineering & Translational Medicine |
| spelling | doaj.art-aca1d621ab66431490d1c4b03729a9b32023-05-17T07:33:11ZengWileyBioengineering & Translational Medicine2380-67612023-05-0183n/an/a10.1002/btm2.10456Megakaryocyte membrane‐wrapped nanoparticles for targeted cargo delivery to hematopoietic stem and progenitor cellsSamik Das0Jenna C. Harris1Erica J. Winter2Chen‐Yuan Kao3Emily S. Day4Eleftherios Terry Papoutsakis5Department of Chemical and Biomolecular Engineering University of Delaware Newark Delaware USADepartment of Materials Science and Engineering University of Delaware Newark Delaware USADelaware Biotechnology Institute University of Delaware Newark Delaware USADepartment of Chemical and Biomolecular Engineering University of Delaware Newark Delaware USADepartment of Materials Science and Engineering University of Delaware Newark Delaware USADepartment of Chemical and Biomolecular Engineering University of Delaware Newark Delaware USAAbstract 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.https://doi.org/10.1002/btm2.10456biomimeticendocytosisgene regulationhematopoietic stem cellsmembrane‐wrappedtargeted delivery |
| spellingShingle | Samik Das Jenna C. Harris Erica J. Winter Chen‐Yuan Kao Emily S. Day Eleftherios Terry Papoutsakis Megakaryocyte membrane‐wrapped nanoparticles for targeted cargo delivery to hematopoietic stem and progenitor cells Bioengineering & Translational Medicine biomimetic endocytosis gene regulation hematopoietic stem cells membrane‐wrapped targeted delivery |
| title | Megakaryocyte membrane‐wrapped nanoparticles for targeted cargo delivery to hematopoietic stem and progenitor cells |
| title_full | Megakaryocyte membrane‐wrapped nanoparticles for targeted cargo delivery to hematopoietic stem and progenitor cells |
| title_fullStr | Megakaryocyte membrane‐wrapped nanoparticles for targeted cargo delivery to hematopoietic stem and progenitor cells |
| title_full_unstemmed | Megakaryocyte membrane‐wrapped nanoparticles for targeted cargo delivery to hematopoietic stem and progenitor cells |
| title_short | Megakaryocyte membrane‐wrapped nanoparticles for targeted cargo delivery to hematopoietic stem and progenitor cells |
| title_sort | megakaryocyte membrane wrapped nanoparticles for targeted cargo delivery to hematopoietic stem and progenitor cells |
| topic | biomimetic endocytosis gene regulation hematopoietic stem cells membrane‐wrapped targeted delivery |
| url | https://doi.org/10.1002/btm2.10456 |
| work_keys_str_mv | AT samikdas megakaryocytemembranewrappednanoparticlesfortargetedcargodeliverytohematopoieticstemandprogenitorcells AT jennacharris megakaryocytemembranewrappednanoparticlesfortargetedcargodeliverytohematopoieticstemandprogenitorcells AT ericajwinter megakaryocytemembranewrappednanoparticlesfortargetedcargodeliverytohematopoieticstemandprogenitorcells AT chenyuankao megakaryocytemembranewrappednanoparticlesfortargetedcargodeliverytohematopoieticstemandprogenitorcells AT emilysday megakaryocytemembranewrappednanoparticlesfortargetedcargodeliverytohematopoieticstemandprogenitorcells AT eleftheriosterrypapoutsakis megakaryocytemembranewrappednanoparticlesfortargetedcargodeliverytohematopoieticstemandprogenitorcells |