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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. 

Hematologic malignancies are a prevalent group of cancers that originate from abnormal hematopoietic stem cells (HSCs) in the bone marrow. As these cells differentiate to produce all blood cell types, their mutation and/or abnormal differentiation results in a wide range of diseases and complications. Current treatments for hematologic maligancies include chemotherapy and HSC transplants, both of which engender detrimental side effects that the patient must endure, and the end result is still often death. Thus, there exists a dire need for alternative methods to treat hematologic malignancies. Researchers have recently begun to explore the use of biomimetic nanotherapeutic to treat these cancers and mitigate their side effects, with promising results. Biomimetic nanoparticles (NPs) imitate naturally occurring structures such as cells through various techniques to avoid immune recognition and target specific locations in the body; by exploiting cells’ expression of “self‐recognition” molecules and their unique homing abilities, biomimetic NPs can deliver therapeutic cargo precisely to diseased cells while minimizing risks of toxicity. Herein, several biomimetic nanomedicines are reviewed that are investigated as treatments for hematologic malignancies and offers perspective on the future of this approach as a therapeutic strategy.