Intelligent Nano-vehicles for Tracking and Selective Immunochemotherapy of Cancer

Samenvatting

Simultaneous visualization of cancer and selective immunochemotherapy could be achieved with minimal side effects, using drug-delivery systems carrying immunochemotherapeutic agents. These vehicles will locate and destroy tumor cells, while simultaneously activating the immune system to eliminate remaining chemo-resistant tumor cells. With this project, we aim to develop intelligent nano-vehicles that harbour three functions combining cancer detection and treatment: i) visualization based on contrast agents that enable real-time monitoring of tumor cells; ii) targeted selective chemotherapy; iii) and immunotherapy by chemotactic attraction and Toll-like receptor activation of immune cells. Therefore, these multifunctional nano-vehicles will comprise: the biodegradable, biocompatible and FDA-approved polymer poly(lactic-co-glycolic) acid (PLGA), for transport and controlled release of the active ingredients; an external layer that will enable selectivity by guiding the nano-vehicles according to receptors that are present on tumor cells; a protective surface layer of polyethylene glycol to prevent non-specific interactions and extend the physiological half-life of the nano-vehicles; encapsulated contrast agents, such as perfluorocarbon, that can be monitored non-invasively by magnetic resonance imaging; chemotherapeutic drugs with established clinical efficacy; chemotactic molecules, which will be released upon degradation of the vehicle at the tumor site to produce a local chemokine gradient that will attract dendritic cells (DCs) subsets; and an inducing maturation and activation agent for the tumor site attracted DCs, to induce an in situ anti-tumor immune response. Our selective immunochemotherapy approach aims to transform the tumor into its own antigenic therapeutic vaccine that, following the tumor-specific chemotherapy, will destroy residual cells in the primary tumor and distant metastases.
Our project will incorporate innovations from chemistry, nanotechnology, medical imaging, and immunology. We envision that these nano-vehicles will mark the advent of a new era of anti-tumor treatments, and that they could be further honed to enable non-invasive monitoring of tumors at different stages of development.

Producten

Wetenschappelijk artikel

  • L.J. Cruz(2014): Targeting nanoparticles to CD40, DEC-205 or CD11c molecules on dendritic cells for efficient CD8+ T cell response: A comparative study Journal of Controlled Release pp. 209 - 218
  • L.J Cruz(2016): Targeted nanoparticles for the non-invasive detection of traumatic brain injury by optical imaging and fluorine magnetic resonance imaging Nano Research pp. 1276 - 1289
  • J Cruz(2016): Combinatorial prospects of nano-targeted chemoimmunotherapy Biomaterials pp. 308 - 320
  • L.J. Cruz(2016): Effect of PLGA NP size on efficiency to target traumatic brain injury Journal of Controlled Release pp. 31 - 41
  • L.J. Cruz(2017): The Potential of Nano-Vehicle Mediated Therapy in Vasculitis and Multiple Sclerosis The Potential of Nano-Vehicle Mediated Therapy in Vasculitis and Multiple Sclerosis pp. 1 - 8

Publieksinformatie

Kenmerken

Projectnummer

723.012.110

Hoofdaanvrager

Dr. L.J. Cruz Ricondo

Verbonden aan

Universiteit Leiden, Leids Universitair Medisch Centrum, Divisie 2

Uitvoerders

Dr. L.J. Cruz Ricondo, Dr. C.E Eich PhD, C.G. da Silva

Looptijd

01/01/2014 tot 31/12/2018