Biomedical Engineering Reference
In-Depth Information
Additionally, previous studies have largely relied on viral vectors to deliver
these therapeutic genes, which are associated with safety concerns 2
and limit
the clinical application of these cytokines.
Targeted delivery of anticancer agents is one of the promising fields in
anticancer therapy. A major disadvantage of anticancer agents is their lack of
selectivity for tumor tissue, which causes severe side effects and results in low
therapeutic efficiency. Therefore, tumor-targeting approaches have been
developed for improved efficiency and minimizing systematic toxicity by
altering the biodistribution profiles of anticancer agents. In recent years,
targeting drug delivery systems (TDDS) have attracted the extensive attention
of researchers. More and more drug/gene targeted delivery carriers, such as
stealth liposomes, 3 magnetic nanoparticles, 4 ligand-conjugated nanoparticles, 5
and ultrasound microbubbles, 6 have been developed and are under investiga-
tion for their tumor target efficiency and effectiveness for cancer treatment
(Table 12.1). 7 However, these drug/gene delivery vehicles are limited by their
several disadvantages. For example, the magnetic nanoparticles have low drug-
loading capacities, non-uniform particle size distributions, and are prone to
form agglomerates that may lead to an occlusion of capillaries. 4 Also, the rapid
recognition and clearance of liposomes themselves from the bloodstream by
the reticuloendothelial system (RES) limits the usefulness of liposomes as drug
carriers (Table 12.1).
Cell-based therapies are emerging as promising therapeutic options for
cancer treatment. However, the clinical application of differentiated cells is
hindered by the difficulty in obtaining a large quantity of cell numbers and
their lack of ability to expand in vitro, as well as the poor engraftment
efficiency to targeted tumor sites. Mesenchymal stem cells (MSCs) have been
attractive cell therapy vehicles for the delivery of agents into tumor cells
because of their capability of self-renewal, relative ease of isolation and
expansion in vitro, and homing capacity, allowing them to migrate toward and
engraft into tumor sites. 8 Several studies have provided evidence supporting
the rationale for genetically modified MSCs to deliver therapeutic cytokines
directly into the tumor microenvironment to produce high concentrations of
antitumor proteins at the tumor sites, which have been shown to inhibit tumor
growth in experimental animal models. The antitumor effects of intravenous
injections of gene-modified MSCs have been demonstrated in lung, brain, and
subcutaneous tumors. 9-12
d n 4 y 3 n g | 1
12.2 Gene Recombination of MSCs
To develop MSCs as therapeutic agents, efficient gene transfer to the cells is
a prerequisite. The strategies for gene delivery into MSCs include using
viral vectors, nonviral vectors, and three-dimensional/reverse transfection
systems.
 
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