Uddannelses- og Forskningsministeriet - EUopSTART - Nanostructured Silicon Particles as Novel Drug Carriers in Oncology

Project: Research

Project Details


The call is aiming at the following specific challenge: Promising pre-clinical nanomedicine proof-of-concepts have been developed for the therapy of cancer, but their translation into clinical therapies remains a major challenge. An important bottleneck is up-scaling under Good Manufacturing Practice (GMP) conditions for the production of the nanomedicines from the pre-clinical laboratory scale to the quantity needed for clinical testing.

The Scope of the Call: The aim is to translate promising novel nano-technology enabled therapies for cancer with pre-clinical proof-of-concept, from a pre-clinical lab stage up to Phase I clinical testing. The project shall start from an established pre-clinical proof-of-concept, with relevant efficacy and toxicity data. The project shall be focused on the translation process, so that ultimately new effective therapies can be introduced to the European healthcare market. An important aspect is the development of a pilot line for scaling-up the production of the nanomedicines and the quality control, taking into account GMP and medical regulatory requirements. Projects may include the later stages of pre-clinical testing and Phase 1 clinical testing, but the latter is not a requirement. Nanopharmaceuticals may be manufactured with either a top-down or a bottom-up approach, using for example self-assembling technology. Applicants must describe, according to industrial criteria, how the various barriers for advancing their new therapy to clinical application will be overcome, including technical, IPR, competitive, commercial and regulatory criteria, with efficacy and toxicity. Attention must be paid to clinical trial design and the foreseen research and commercial path to market introduction has to be well outlined.

Our project aims at developing nanostructured silicon particles as novel drug carriers in oncology. More specifically, we are aiming at the preclinical development of novel prototype medicines for the targeted delivery of anticancer dugs to solid tumors and/or the sustained delivery of peptide hormones (or their antagonists) suited to suppress the growth of sexual hormone-dependent tumors. The drug/hormone candidate(s) to be chosen for the project will be the ones already recognized to be effective in cancer treatment though clinical trials but which would benefit further from an effective delivery system. A good example of this type of drug is vincristine that is nowadays successfully used against various blood cancers but lacks of suitable targeted carrier system against solid tumors. Nanostructured silicon particles in the sub-micron size range have recently been demonstrated being useful as a novel type of drug carrier. Their versatility in morphology and surface characteristics opens up for a range of drug transport applications. In the project, which we are going to apply funding for from the Horizon2020 program, we are aiming at the following feature of the drug loaded into nanostructured silicon particles: the sustained release of the drug and consequently its protection against premature elimination and degradation in the blood stream or at the site of injection. Our own work (VP Lehto and collaborators) as well as that of others indicate that is feasible to load a variety of small therapeutic moieties, with characteristics similar to conventional anticancer drugs and large therapeutic peptides into nanostructured silicon particles and influence their release characteristics. Furthermore, from our work (M. Brandl and collaborators) as well as the work of others it is known for various kinds of nanoparticulate drug carriers that they accumulate in solid tumors via the “enhanced permeability and retention effect”. It is well established that such accumulation helps to enhance efficacy and reduce toxicity of anticancer drugs. In order to further promote the targeting, the nanoparticles can also decorated with targeting moieties like antibodies or peptides. This type of functionalization has been shown by VP Lehto and coworkers to be rather easy to be realized compared to other usually utilized nanoparticulate systems due to the inorganic nature of the nanostructured silicon. Also, other functionalities like imaging modalities were shown to be feasible to be attached to the drug carrier. We are convinced that there is good early-stage preclinical proof of concept that nanostructured silicon particles represent a promising novel type of nanotechnology. As part of the described project we wish to enter late-stage preclinical testing in preparation for translation into clinical therapies. At the same time we are aiming at overcoming important bottlenecks, such as up-scaling under Good Manufacturing Practice (GMP) conditions for the production of the nanomedicine from the preclinical laboratory scale to the quantity needed for clinical testing.
Effective start/end date01/07/201408/09/2015