DREAM

Main Area
Nanotechnologies

Acronym
DREAM

Project Name
Drug delivery nanosyste for HPV infection therapy Nanotechnologies

Reference
UTAP-EXPL/NTec/0015/2017

Team


 

Carla Cruz
Principal Investigator
in Portugal

 

 

Andrew Ellington
Principal Investigator
in Austin

Keywords
AS1411 derivatives G-quadruplex
Nucleolin
Vehicles-drugs
HPV

Abstract
High risk human papillomaviruses (HPVs) are responsible for over 70% of all cervical cancer cases worldwide, as well as other anogenital cancers in both women and men. The need remains for an efficient treatment of patients with HPV. The nanotechnology applied to viral infection and cancer treatment has a tremendous potential for developing next-generation therapeutics. Specifically, DNA nano-based drug carriers for antiviral and/or anticancer drugs greatly enhance their bioavailability and increase their target specificity. AS1411 is a G-quadruplex (G4)-forming DNA oligonucleotide that functions as an aptamer of nucleolin (NCL), a protein that is present at high levels on the surface of cancer cells. Clinical trials of AS1411 have indicated that it is well tolerated with evidence of therapeutic activity, but improved pharmacology and potency may be required for optimal efficacy. To this purpose, the production of AS1411 derivatives with chemical modifications (introduction of Locked Nucleic Acid and uracil derivatives) will be first addressed, aiming at improving the binding affinity to NCL and their pharmacological properties. To promote the endosomal escape and release of the ligands into the cytoplasm of cancer cells, the AS1411 derivatives will be conjugated to AuNP peptides known for causing endosome disruption. DREAM seeks to use the actual lines of research of the national and international groups involved (which already have a strong background in the development of nanosystems), deepening it to develop a novel vehicle-ligand with antiviral and antitumoral effect in precancerous cells infected by HPV.

Leading Institution
Universidade da Beira Interior (UBI)

Participating Institutions
Associação do Instituto Superior Técnico para a Investigação e Desenvolvimento (IST-ID)
Centro Hospitalar da Cova da Beira (CHCB)
Labfit - Health Products Research and Development Lda (HPRD Lda)

Duration
12 months