Targeted Delivery of siRNA Lipoplexes to Cancer Cells Using Macrophage Transient Horizontal Gene Transfer

Wayne, Elizabeth; Long, C. Tyler; Haney, Matthew J.; Batrakova, Elena V.; Leisner, Tina M.; Parise, Leslie V.; Kabanov, Alexander V.

doi:10.1002/advs.201900582

Cited by 64 publications

(44 citation statements)

References 68 publications

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“…Thus, pre-transfected macrophages serve as “donors” that pass or “horizontally transfer” the gene to acceptor cells. In this respect, we demonstrated recently that transfected macrophages can pass p DNA to muscle cells 55 , and siRNA to cancer cells 56 , causing significant antitumor effects. In addition, GDNF-BMM can also deliver the overexpressed neurotrophic factor.…”

Section: Discussionmentioning

confidence: 99%

Genetically modified macrophages accomplish targeted gene delivery to the inflamed brain in transgenic Parkin Q311X(A) mice: importance of administration routes

Haney

Zhao

Fay

et al. 2020

Sci Rep

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Cell-based drug delivery systems have generated an increasing interest in recent years. We previously demonstrated that systemically administered macrophages deliver therapeutics to CNS, including glial cell line-derived neurotrophic factor (GDNF), and produce potent effects in Parkinson’s disease (PD) mouse models. Herein, we report fundamental changes in biodistribution and brain bioavailability of macrophage-based formulations upon different routes of administration: intravenous, intraperitoneal, or intrathecal injections. The brain accumulation of adoptively transferred macrophages was evaluated by various imaging methods in transgenic Parkin Q311(X)A mice and compared with those in healthy wild type littermates. Neuroinflammation manifested in PD mice warranted targeting macrophages to the brain for each route of administration. The maximum amount of cell-carriers in the brain, up to 8.1% ID/g, was recorded followed a single intrathecal injection. GDNF-transfected macrophages administered through intrathecal route provided significant increases of GDNF levels in different brain sub-regions, including midbrain, cerebellum, frontal cortex, and pons. No significant offsite toxicity of the cell-based formulations in mouse brain and peripheral organs was observed. Overall, intrathecal injection appeared to be the optimal administration route for genetically modified macrophages, which accomplished targeted gene delivery, and significant expression of reporter and therapeutic genes in the brain.

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Section: Discussionmentioning

confidence: 99%

Genetically modified macrophages accomplish targeted gene delivery to the inflamed brain in transgenic Parkin Q311X(A) mice: importance of administration routes

Haney

Zhao

Fay

et al. 2020

Sci Rep

Self Cite

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“… 20 Nanoporous silicon particles were later encapsulated with purified mononuclear macrophage membranes, resulting in materials with macrophage-like functions. 21 Based on these encouraging findings, the application of macrophages as carriers for the delivery of drugs with different properties has been significantly expanded in order to study and treat various conditions such as cancer, 22 inflammation, 23 and HIV infection 24 ( Table 1 ).…”

Section: Development Of Macrophage-mediated Drug Delivery Systemsmentioning

confidence: 99%

Recent Advances in Macrophage-Mediated Drug Delivery Systems

Liang

Zhang

Liu

et al. 2021

IJN

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Macrophages have been extensively used in the development of drug delivery systems, as they can prolong the circulation and release of drugs, extend their half-life, increase their stability and targeting ability, and reduce immunogenicity. Moreover, they have good biocompatibility and degradability and offer abundant surface receptors for targeted delivery of a wide variety of drugs. Macrophage-mediated drug delivery systems can be prepared by loading drugs or drug-loaded nanoparticles into macrophages, macrophage membranes or macrophage-derived vesicles. Although such systems can be used to treat inflammation, cancer, HIV infection and other diseases, they require further research and optimization since they have been assembled from diverse sources and therefore can have quite different physical and chemical properties. Moreover, potential cell-drug interactions can limit their application, and the biological activity of membrane proteins might be lost during membrane extraction and storage. In this review, we summarize the recent advances in this field and discuss the preparation of macrophage-mediated drug delivery systems, their advantages over other delivery systems, their potential applications and future lines of research.

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“…Furthermore, side scattering was recorded to confirm the granularity of macrophages (Ch6, 762/35). The liposome uptake was imaged in green fluorescence (Ch02, 528/65 nm) after 4, 6, 12, 18 and 24 h. Untreated live and dead cells were also imaged, as negative and positive controls, respectively, to adjust for auto-fluorescence and validate the gating tree [43].…”

Section: Flow Imagingmentioning

confidence: 99%

Following the Fate of Dye-Containing Liposomes In Vitro

Cauzzo

Nystad

Holsæter

et al. 2020

IJMS

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The rather limited success of translation from basic research to clinical application has been highlighted as a major issue in the nanomedicine field. To identify the factors influencing the applicability of nanosystems as drug carriers and potential nanomedicine, we focused on following their fate through fluorescence-based assays, namely flow cytometry and imaging. These methods are often used to follow the nanocarrier internalization and targeting; however, the validity of the obtained results strictly depends on how much the nanosystem’s fate can be inferred from the fate of fluorescent dyes. To evaluate the parameters that affect the physicochemical and biological stability of the labeled nanosystems, we studied the versatility of two lipid dyes, TopFluor®-PC and Cy5-DSPE, in conventional liposomes utilizing well-defined in vitro assays. Our results suggest that the dye can affect the major characteristics of the system, such as vesicle size and zeta-potential. However, a nanocarrier can also affect the dye properties. Medium, temperature, time, fluorophore localization and its concentration, as well as their interplay, affect the outcome of tracing experiments. Therefore, an in-depth characterization of the labeled nanosystem should be fundamental to understand the conditions that validate the results within the screening process in optimization of nanocarrier.

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Targeted Delivery of siRNA Lipoplexes to Cancer Cells Using Macrophage Transient Horizontal Gene Transfer

Cited by 64 publications

References 68 publications

Genetically modified macrophages accomplish targeted gene delivery to the inflamed brain in transgenic Parkin Q311X(A) mice: importance of administration routes

Genetically modified macrophages accomplish targeted gene delivery to the inflamed brain in transgenic Parkin Q311X(A) mice: importance of administration routes

Recent Advances in Macrophage-Mediated Drug Delivery Systems

Following the Fate of Dye-Containing Liposomes In Vitro

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