BASIC DATA OF THE RESEARCH PROJECT
- ARRS code: J4-50150
- TITLE: Erythrocyte membrane-based nanocarriers for gene silencing cancer therapy
- PRICE CLASS: D
- PROJECT LEADER: Boštjan Markelc, PhD
- APPLICANT RESEARCH ORGANISATION: Institut “Jožef Stefan”
- PARTICIPATING RESEARCH ORGANISATIONS: Institute of Oncology Ljubljana
- DURATION: 1.10.2023 – 30.9.2026
- FINANCING: Slovenian Research and Innovation Agency
ABSTRACT
This proposal addresses new concepts in cancer treatment and diagnostics based on a multi-functional biomimetic nanosystem made of body's own cells as drug carriers. Disguised with cell membranes, the nanoparticles or other active components can act as autogenous cells and thus ensure the inherent biocompatibility and increase the circulation time. Therefore, we propose to use red blood cell membranes (RBCMs) as a drug delivery system. The proposed biomimetic system will enable gene therapy of tumour metastases by delivering siRNA for gene silencing and photothermal therapy. To realize this, the RBCMs will be encapsulated with:
- siRNA for gene silencing cancer therapy and
- indocyanine green (ICG) that enables both photothermal treatment and fluorescent imaging
As tumors depend on angiogenesis, targeting endoglin, an endothelial cell marker, has potential in the treatment of solid tumours, as well as metastasis in both breast and colon cancers. Our membrane-based carriers will be evaluated in terms of biodistribution and gene delivery efficacy. The project is organized sequentially towards the final goal – the development of a preclinical proof-of-concept-efficient theranostic system. In the first part of the project, the focus will be on the synthesis and ex vitro evaluation of the performance of each active component separately before constructing the final hybrid system. The special task will be dedicated to the characterization of membrane-carriers in terms of membrane composition and compared to the membrane composition of original cells, which is crucial to ensure non-immunogenicity and long circulation time of RBCMs. In the second part of the project, in vitro testing on normal and cancerous cells will be performed to evaluate the cytotoxicity and the cellular uptake of each individual component and RBCMs containing siRNA and ICG. Finally, siRNA gene silencing efficiency will be evaluated. Based on the extensive in vitro experiments, the final ICG/siRNA-RBCMs will be designed and used for the subsequent in vivo testing. Biodistribution and pharmacokinetics of intravenously injected nanocarriers and their potential for gene silencing will be determined. Similar reports can be found with synthetic liposomes, but the as-proposed nanosystem with a biomimetic RBCMs is a complete novelty and represents a huge step forward in this newly evolving field of biomimetic theranostic nanomedicine. Moreover, photothermal treatment will be used as adjuvant to gene therapy to improve the outcome of the treatment.