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Abstract The paucity of targeted therapies for triple‐negative breast cancer (TNBC) causes patients with this aggressive disease to suffer a poor clinical prognosis. A promising target for therapeutic intervention is the Wnt signaling pathway, which is activated in TNBC cells when extracellular Wnt ligands bind overexpressed Frizzled7 (FZD7) transmembrane receptors. This stabilizes intracellular β‐catenin proteins that in turn promote transcription of oncogenes that drive tumor growth and metastasis. To suppress Wnt signaling in TNBC cells, this work develops therapeutic nanoparticles (NPs) functionalized with FZD7 antibodies and β‐catenin small interfering RNAs (siRNAs). The antibodies enable TNBC cell specific binding and inhibit Wnt signaling by locking FZD7 receptors in a ligand unresponsive state, while the siRNAs suppress β‐catenin through RNA interference. Compared to NPs coated with antibodies or siRNAs individually, NPs coated with both agents more potently reduce the expression of several Wnt related genes in TNBC cells, leading to greater inhibition of cell proliferation, migration, and spheroid formation. In two murine models of metastatic TNBC, the dual antibody/siRNA nanocarriers outperformed controls in terms of inhibiting tumor growth, metastasis, and recurrence. These findings demonstrate suppressing Wnt signaling at both the receptor and mRNA levels via antibody/siRNA nanocarriers is a promising approach to combat TNBC. 

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. 

Abstract Significant advances have been made in the development of nanoparticles for cancer treatment in recent years. Despite promising results in preclinical animal models, cancer nanomedicines often fail in clinical trials. This failure rate could be reduced by defining stringent criteria for testing and quality control during the design and development stages, and by performing carefully planned preclinical studies in relevant animal models. This article discusses best practices for the evaluation of nanomedicines in murine tumor models. First, a recommended set of experiments to perform is introduced, including discussion of the types of data to collect during these studies. This is followed by an outline of various tumor models and their clinical relevance. Next, different routes of nanoparticle administration are overviewed, followed by a summary of important controls to include in in vivo studies of nanomedicine. Finally, animal welfare considerations are discussed, and an overview of the steps involved in achieving US Food and Drug Administration approval after animal studies are completed is provided. Researchers should use this report as a guideline for effective preclinical evaluation of cancer nanomedicine. As the community adopts best practices for in vivo testing, the rate of clinical translation of cancer nanomedicines is likely to improve.