The live-cell drug delivery using monocytes loaded chemotherapeutic nanoparticles Akihiro Maeda1, Roberta Avigni1, Barbara La Ferla2, Fernando Torres Andon1, Paola Allavena1 1IRCCS Humanitas Clinical and Research Center; 2Department of Biotechnology and Biosciences, University of Milano-Bicocca
The drug delivery system has been studied in these several decades, improving targeting and efficacy of chemotherapeutics delivery, such as targeting peptides, nanoscale drug carriers or controlled drug release. In this study, we employed a live-cell drug delivery (LCDL) strategy using monocytes loaded with chemotherapeutic nanoparticles. It is well established that circulating blood monocytes are actively recruited at peripheral tumor sites where they differentiate in Tumor-Associated Macrophages (TAMs). We exploited their tissue penetration ability to set up a possibly useful tool for tumor targeting therapy. We used a nanotechnological approach to load anti-tumor chemotherapeutics into blood-isolated monocytes, thus protecting them from drug toxicity. For this purpose, we chose the poly (lactic-co-glycolic acid) nanoparticles (PLGA-NP), which are approved by the US Food and Drug Administration (FDA) for the use of drug delivery, due to their biocompatibility and biodegradability. Using fluorescent PLGA-NP we confirmed their significant engulfment by human and mouse monocytes with intra-cellular stability for up to 48 h, and stable size (around 150 nm) and Z-potential (-30 mV). Upon demonstration that human primary monocytes are able to migrate in vitro in response to mouse fibrosarcoma supernatant, we subsequently examined if human monocytes injected into fibrosarcoma-bearing mice are recruited at tumor site in vivo. Two days after injection we indeed observed significant migration of fluorescent monocytes into tumor tissues. These initial results are encouraging and suggest that this LCDL strategy may be useful as a new of anti-tumor strategy.
Funding This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 706557.
Credits: None available.
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