UC San Diego

Modern medicine has achieved extraordinary results with the use of nanotechnologies. The combination of the two disciplines created the modern field of nanomedicine, in which drug delivery is one of the most prominent branches. Several aspects are involved in drug delivery; this work will focus on the drug delivery vehicle. In particular three aspects will be investigated: building material, internal structure and material compatibility. In a first project DNA was proposed as an innovative building material. DNA nanoparticles were made from self-folding of long concatameric repeats of a single strand sequence. Nanoparticles with different sequences created a library that was bio- panned against dendritic cells (DC). Particles from the enriched library were sequenced and individually tested for affinity towards DC. The use of DNA as building material offers several advantages. For instance DNA binding drugs (such as Doxorubicin) can be easily incorporated, and immunostimulatory sequences (such as GpC) and any other encoding sequence can be integrated within the concatamers. In addition, any other molecule or small particle of interest can be conjugated to a short complementary sequence and hybridized on the outer layer of the DNA nanoparticle. DNA nanoparticles' payloads are limited to hydrophilic drugs. In addition to an hydrophobic payload, some therapies require a high loading and steady release. To achieve such results a gradient structure was created within the core of a polymeric nanoparticle. Physical and chemical gradient were considered. A chemical gradient was created by combining a low molecular weigh polycaprolactone (PCL) to a higher molecular weigh poly(lactic-co-glycolic acid) (PLGA). PCL and PLGA have different degradation rate and hydrophobicity. The particles created by combining the two polymers showed properties (such as loading) dependent on the two polymers' proportion into the composition. The chemical gradient nanoparticles are characterized by high loading and steady release of hydrophobic drugs. A new technique was examined to encapsulate hydrophilic oligonucleotides into hydrophobic nanoparticles. PMAL-C8, a zwitterionic polymer, interacts with oligonucleotides of different length and improves their loading into the hydrophobic core. The nanoparticles created were successfully used in transfection experiments, showing the bioavailability of the loaded oligonucleotides