Periodic Reporting for period 1 - PepPtNPAntiCan (Peptide Coated Platinum Nanoparticles as Antitumor Agents)
Reporting period: 2016-03-01 to 2018-02-28
Cisplatin is an efficient chemotherapeutic drug, yet it suffers from two main disadvantages: evolving drug resistance and relatively high toxicity. There is therefore a need to develop successful candidates for anticancer treatments with reduced toxicity and improved activity. One of the latest approaches for dealing with these drawbacks has been the development of platinum nanoparticles (PtNPs) as a source of Pt(II) ions. However, this solution is far from effective, mainly due to obstacles in cancer cell targeting and a lack of nuclear penetration.
The overall objectives of this project were to form PtNPs in a straight forward process that have high cytotoxicity and tumor selectivity.
The overall objectives of this project were to form PtNPs in a straight forward process that have high cytotoxicity and tumor selectivity.
We have developed peptide-coated PtNPs that are stable for more than 12 months, both as a suspension in water and as a dry powder. The peptide was identified from a combinatorial screening of more than 3000 different sequences and further optimized to provide for high water solubility and long-time stability of the PtNPs. The PtNPs form in a single step and are small and monodisperse. In addition, they were formed in water at room temperature. They were also covalently functionalized with moieties that allow for monitoring and improving their cellular uptake, before and also after PtNP formation. This resulted in PtNPs that exhibit high cytotoxicity and specificity for certain types of carcinoma cells.
Based on the successful in vitro results, we are currently pursuing further in vivo investigation, if successful, we expect these PtNPs to be patented and be further investigated toward pharmaceutical application. In this case, the potential impact of such system can be enormous in the field of chemotherapeutics.