An Insulin-Gold Nanoplatform as Enhanced Antibody-Drug Conjugate Cancer Therapy

Descripción del proyecto

Nanoplataforma de oro e insulina para el tratamiento antineoplásico dirigido

Los anticuerpos conjugados a fármacos (ACF o ADC, por sus siglas en inglés) son un tipo de tratamiento antineoplásico prometedor que actúa de forma selectiva sobre los tumores sin afectar al tejido sano. No obstante, problemas relacionados con su diseño y administración limitan su eficacia contra los tumores sólidos. En el proyecto Golden-ADC, financiado por el Consejo Europeo de Investigación, se pretende abordar esas limitaciones desarrollando nanopartículas de oro que aprovechen la insulina para administrar fármacos de tamaño molecular grande, incluidos anticuerpos, a través de barreras biológicas. Investigaciones recientes han demostrado que las nanopartículas de oro e insulina pueden servir como nanoplataforma para ACF al favorecer la conjugación eficaz de diferentes anticuerpos y fármacos. Esta plataforma ha demostrado su eficacia en modelos celulares de cáncer, ya que mejora la acumulación, penetración y distribución tumoral. El proyecto se centrará en probar la nanoplataforma para el tratamiento del cáncer de mama triple negativo, una enfermedad para la que aún hoy no se dispone de terapias eficaces.

Objetivo

Antibody-drug conjugates (ADCs) have emerged as promising therapies by combining the precision targeting abilities of antibodies with the potency of chemotherapy drugs, to directly attack cancer cells and minimize damage to healthy tissue. However, approved ADCs show low efficacies in treating solid tumours, due to inherent challenges. These include design challenges, which limit the drug-antibody ratio and the ability to integrate multiple drug types, and delivery challenges, in which pharmacokinetics and tumor barriers limit ADC accumulation and distribution within tumours.
In the framework of the ERC-CoG project, we are developing gold nanoparticles (GNPs) that harness insulin for delivery of large therapeutics, including antibodies, across biological barriers. As part of this research, we have recently revealed that these insulin-GNPs can be further developed as an ADC nanoplatform. This Golden-ADC nanoplatform enables simple conjugation of large payloads of multiple antibodies and drug types, shows efficacy in cancer cell models, and enhances in vivo tumor accumulation, together with deep penetration and wide distribution throughout the tumour.
In this PoC proposal, we will test our Golden-ADC nanoplatform for effective and safe treatment of triple negative breast cancer, due to the potential high benefits that our nanoplatform can provide for this hard-to-treat cancer, which has a long-standing paucity of effective therapies. Within GOLDEN ADC, we aim to acheive significant progress in the technology development process, by proof of concept demonstration of efficacy and safety of the Golden-ADC conjugated with multiple drugs in in-vivo triple negative breast cancer models. We also intend to achieve business readiness, via consolidating the IP strategy, undertaking a comprehensive market analysis, end-user engagement and developing the business strategy.