Nano-bioengineering for Drug and Gene Delivery

Title: Nano-bioengineering for Drug and Gene Delivery

Speaker: Kyeil Joo -  SUNUM G11

Optimal treatment by many drugs often requires maintenance of the drug level for a prolonged time in
order to achieve the therapeutic goals. Nanoparticle-based drug delivery systems, which possess
capability of modulating drug release profile and improving drug circulation, have been widely viewed
as a new treatment option for many therapeutic drugs. Especially for cancer treatment, the ability of
nanoparticles to accumulate in tumor microenvironment has resulted in development of various
therapeutic nanoparticles for clinical use. Liposomes are one of most popular nanocarrier, however,
inherent instability in the presence of serum components and limited drug loading have remained
prohibitive obstacles in their utility for the delivery of anticancer agents. To overcome theses
challenges, I have developed a novel nanotechnology platform (CML) that involves generating a
robust multi-layered structure of nanoparticles, which could remarkably improve vesicle stability that
enables release of entrapped drugs in a controllable and sustainable manner in a serum environment.
I have demonstrated that this engineered nanoparticle system is capable of co-delivery of multiple
hydrophilic/hydrophobic drugs for inducing synergistic antitumor activity, which can be readily adapted
as effective treatment options for diseases with unmet medical needs.
As a consequence of their well-defined nanostructure and intrinsic bioactive functionality, virus-based
nanoparticles have shown promise for mediating gene delivery. Among various viral nanoparticles,
adeno-associated virus (AAV) has been considered as a promising vehicle for human gene therapy
based on its ability to infect both dividing and nondividing cells, as well as establish long-term gene
expression in vivo without known pathological consequence of infection. Although AAV nanovectors
possess a high safety profile and remarkable potential in several disease models, their utilization in
many areas of gene therapy is limited by the restricted tissue tropism of AAV. Therefore, retargeting
the viral particle tropism of AAV to desired target cells could not only expand its utility for gene
delivery applications, but also mitigate safety issues for use in human gene therapy. In this seminar,
the general strategies that I have established for retargeting viral nanoparticles will be discussed in
more detail.
In addition, ineffective uptake of drug/gene delivery vectors to target cells in vivo environment always
remains obstacles for the clinical translation of the therapeutic vectors. I have developed a general
strategy for in vivo modulation of target cells using a biomaterial scaffold by creating optimal in vivo
microenvironment where target cells can be recruited and proliferated. This method could remarkably
enhance drug/gene delivery efficacy to the target cells in vivo. Many components of the therapeutic
strategy proposed in these researches will be presented in the seminar.