Inno-Indigo: Nanoplatform-based drug delivery system: combinational therapy against breast and colorectal cancer

One of the major causes of failure of conventional chemo-therapies is the poor entry of anti-cancer drugs into tumors. In this context, tumor targeting by nanomedicine-based therapeutics has emerged as a promising approach to overcome the lack of specificity of conventional chemotherapeutic agents. Another major challenge in chemotherapy is loss of therapeutic efficacy through acquired drug resistance. This phenomenon, called multidrug resistance, is found in up to 50-70% of breast cancer patients undergoing chemotherapy. Furthermore, it is known that most tumors consist of a heterogeneous population of cancer cells which respond differently to a certain anti-cancer drug. In this project, we loaded biodegradable lipid nanocapsules with anti-cancer drugs to achieve a a good therapeutic effect. Multiple challenges must be overcome in such a project and we established an interdisciplinary cluster of experts in the fields of nanoparticle synthesis, pharmacy, cell biology, and human tumor models in mice. The studies have resulted in two manuscript, the first was recently submitted for publication and the second manuscript is expected to be submitted a couple of months after the end of this project.

Forskningsgruppene i prosjektet har oppnådd gode nytteeffekter og bygd tverrfaglig kompetanse innen preklinisk dokumentasjon av biologisk nedbrytbare lipid nanokapsler (LNCs). Disse nanopartikelene er blitt optimalisert gjennom iterative prosesser basert på resultater i celleforsøk og dyremodeller. I tillegg til de vitenskapelige data som er oppnådd og som nå sendes for publisering har prosjektet også bidratt til kompetansebygging for flere forskere innen den type studier som utføres i Sandvig-gruppen ved at to unge gjesteforskere fra Giri-gruppen i Hyderabad arbeidet to måneder i Sandvig-laben. Dette oppholdet medførte også kunnskapsoverføring om produksjon av LNC-partikler fra Giri-gruppen til Sandvig-gruppen. Prosjektresultatene er lovende og danner et godt grunnlag for videreutvikling av LNC-partikler til målrettet levering av anti-kreftmedisin. Prosjektet har skapt oppmerksomhet om fagmiljøene og skaffet oss nye internasjonale samarbeidspartnere for fremtidig forskningssamarbeid.

This project aims at using the lipid nanocapsule (LNC) drug delivery system we have recently developed for treatment of breast and colon cancer. The LNCs have a superior ligand binding capability on the surface and can load a broad range of drug molecules. Our approach is to develop a novel LNC based delivery system as an all-in-one solution due to the following issues: (i) A significant portion of the drug molecules end up in normal organs, rather than accumulating at tumor sites, causing severe side effects and limiting the dosage of the therapeutic regimen. (ii) There is a loss of therapeutic efficacy over the course of treatment, through acquired drug resistance. This phenomenon, called multidrug resistance, is found in up to 50-70% of breast cancer patients undergoing chemotherapy. The LNC with multimodal strategies of tumor targeting (both passive targeting via EPR and active targeting by adding small molecules), combinational therapeutic treatment (delivery of drugs for killing cancer cells including cancer stem cells and reducing drug resistance) along with capabilities of MRI based detection will revolutionize cancer treatment. The physico-chemical properties of the LNC will be optimized and functionalized with cyclic-RGD to enhance the therapeutic effect on tumors. We will load small paramagnetic irion oxide nanoparticles with drug molecules to integrate therapeutic and imaging functions, which can be used as cancer theranostic and personalized medicine. This project will provide a novel nano-vehicle system for delivery of important cancer drugs and also provide effective treatment of cancer by including different drugs within the same nanoparticle.