6 months Internship: Controlled and targeted photothermal delivery of CDK4 inhibitors by Prussian Blue nanoparticles into cellular and ex ovo models of pancreatic cancer.
Pancreatic cancer (PC) has a less than 1% overall 10-year survival rate and is typically diagnosed at an advanced stage with limited treatment options. Surgical resection remains the only potentially curative treatment, generally followed by adjuvant chemotherapy. For non-resectable metastatic PC, current chemotherapy regimens provide limited benefit and are associated with significant toxicity. In addition, the dense stromal environment of PC tumors restricts drug penetration, highlighting the need for innovative therapeutic strategies. This proposal focuses on developing new nanomedicines targeting PC by encapsulating drugs that inhibit CDK4 kinase in photothermal Prussian Blue nanoparticles (PBNP) allowing controlled drug release. Building on the expertise and existing proofs-of-concepts developed at ICGM (PBNP engineering, photothermal activation) and IBMM (kinase inhibitors and biosensors, PC cell and ex ovo models), the project will investigate whether irradiation-triggered delivery can improve the efficacy and selectivity of kinase inhibitor treatment while addressing the major limitations associated with conventional drug administration. The collaboration brings together complementary expertise in nanochemistry, photothermal nanomaterials, biochemistry, kinase-targeted therapeutics, cancer biology and ex ovo models using the chicken chorioallantoic membrane (CAM). This multidisciplinary approach will enable the rational design and evaluation of nanoparticle/drug formulations, from their physicochemical characterization and light-triggered drug release to their biological validation in relevant PC models, ultimately paving the way towards innovative therapeutic strategies for pancreatic cancer.
Specifically, the M2 student will be involved in three tasks in collaboration with both teams at ICGM and IBMM, thereby acquiring interdisciplinary expertise in chemistry and biology:
- Engineering of PBNP/drug systems and physico-chemical characterization of drug loading and release following irradiation
- Characterization of the PBNP/drug efficacy to inhibit CDK4 and proliferation of cultured PC cell lines following irradiation
- In-vivo evaluation of the efficacy of PBNP/drugs in ex ovo CAM models of PC following irradiation
Profile Sought:
We are seeking a Master 2 (or 3rd-year ENSCM student) with a background in chemistry or biology and an interest in interdisciplinary research. Depending on their background, the student will have the opportunity to develop existing skills and acquire new knowledge and expertise relevant to the project, including nanoparticle synthesis, characterization and/or biological evaluation. Good organizational skills, experimental rigor, scientific curiosity, enthusiasm and motivation will be essential. The ability to write and present scientific work will be appreciated.
Références
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