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HEIndividual fellowship2023–2025

MAGNOSTICS · Biomimetic MAGnetic nanoparticles with homotypic targeting for combinatorial theraNOSTICS of triple-negative breast cancers

Horizon Europe — Marie Skłodowska-Curie Actions

Duration
2023-05-02 → 2025-05-01
EU contribution
€172,619
Participants
1
Scheme
HORIZON-TMA-MSCA-PF-EF

Lines connect the coordinator with its partners.

Results in brief

Biomimetic MAGnetic nanoparticles with homotypic targeting for combinatorial theraNOSTICS of triple-negative breast cancers

MAGNOSTICS aimed at developing biomimetic platform for the targeted delivery of siRNA against ABCB1 gene and anti-cancer drug to achieve a multi-modal thernaostics for triple negative breast cancer (TNBC). Metastatic TNBCs are aggressive tumors with poor prognosis contributing to about 15 % of all the breast cancers with high mortality rates. Characterized by the absence of estrogen, progesterone, and human epidermal growth factor 2 receptors, endocrine and targeted therapies are ineffective. Thus, chemotherapy is still the cornerstone for TNBC treatment. However, chemotherapy is strongly impeded by non-specificity and efflux/drug resistance, which lead to recurrence and relapse. In metastatic cases, 90% of therapy failure is attributed to chemoresistance. ATP-binding cassette (ABC) transporters are one of the strong reasons leading to drug efflux and thus chemoresistance. Suppressing the expression of ABCB1 gene with a small-interfering RNA (siRNA) can inhibit drug efflux. A combined treatment approach addressing drug efflux with superior synergistic effect is required for the improved management of TNBCs. Through MAGNOSTICS, we aimed to develop multimodal biomimetic nanoplatform to address non-specificity and ABCB1-mediated chemoresistance in TNBC. Thus, the objectives of MAGNOSTICS were to synthesize and characterize biomimetic magnetic iron-oxide nanoparticles (MNPs) loaded with the anticancer drug, doxorubicin (Dox) and siRNA against ABCB1 gene with a coating of cancer cell membrane (CM) obtained from a drug-resistant TNBC cell line. Through MAGNOSTICS, the biomimetic nanoparticles (NPs) were found to be biocompatible, demonstrated efficient uptake by cancer cells, and displayed immune escape capability. Importantly, these biomimetic NPs showed excellent gene silencing and retention of dox. Furthermore, with the magnetic hyperthermia, the NPs demonstrated enhanced siRNA release and as MRI contrast agents.

Data: CORDIS, © European Union

Project objective

Cancer is a leading cause of death and is a major impediment to increasing life expectancy around the globe. Amongst all breast cancers (BC), triple-negative breast cancers (TNBCs), are of much concern, as chemotherapy is the only option. However, it is associated with chemoresistance owing to drug efflux. Moreover, since TNBCs are negative for estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER 2), treatment strategies targeting these receptors do not work. Combined strategies for TNBCs have strong potential in treating TNBCs, as compared to singular approaches. Thus, MAGNOSTICS aims to develop biomimetic cancer cell membrane (CCM) coated magnetic nanoparticles for chemotherapy, gene targeting, and magnetic hyperthermia as a triple strategy for TNBC therapy. In addition, MAGNOSTICS proposes multimodal theranostics incorporating MRI enabled by MNPs. To promote cellular uptake and immune escape, MNPs will be loaded with CDDP and siRNA and camouflaged with CCM derived from TNBC cells. CCM coating will utilize the homotypic targeting strategy for self-recognition and uptake of NPs. Thus, the objectives are; i) to synthesize and characterize CCM coated MNPs conjugated with CDDP and siABCB1, ii) to study the biocompatibility/uptake and single therapeutic strategies as proof-of-concept in 2D cell cultures, iii) To develop 3D multicellular tumor spheroids and demonstrate the effectiveness of camouflaged NPs as combined theranostic platform; iv) to ensure further professional development of the ER through training, dissemination and public engagement. MAGNOSTICS thus aims to improve TNBC treatment and impact society with the right term and place.

Original text from CORDIS.

Participants

  • INTERNATIONAL IBERIAN NANOTECHNOLOGY LABORATORY · BragaCoordinatorPortugal

Links

Data: CORDIS, © European Union