1 3
Topics in Current Chemistry (2020) 378:13
part of liposome formation [135]. Various examples of MNP applications in gene
delivery that have been reported in the literature are shown in Table 3.
Plasmids can be used not only as disease treatment, but also as a vaccination system for genetic immunization. A DNA vaccine is a third-generation vaccine that
incorporates a vector with a eukaryotic cell promoter and a gene that encodes for
an immunogenic protein. In contrast with protein-based traditional vaccines, DNA
vaccination has the capacity to induce both cellular and humoral immune responses.
The structure of plasmid DNA provides some advantages over other traditional
protein-based or carbohydrate-based vaccines since plasmid DNA can encode
many immunogenic proteins of the same virus and can also encode similar proteins
belonging to different infective agents [145]. Other important advantages of DNA
vaccines are their easy assembly, stability at room temperature, ease of manipulation, and low cost of plasmid production. However, the remaining challenges are to
increase transfection efficiencies and facilitate intracellular uptake and to improve
targeting to cells, as well as to perform these operations with small amounts of
DNA. Various gene delivery and adjuvant systems at the nanoscale are used to overcome these problems. During the use of a nanotechnological adjuvant, the degradation of DNA is prevented, resulting in ultra-rapid delivery by targeting to the desired
cells [146].
Adjuvants are generally grouped into two subtypes, namely, molecular adjuvants,
which are immunostimulants, and carrier structures, which are systems that control
release (e.g., mineral salts, liposomes, biodegradable polymers, and micro/nanoparticles). The use of cationic polymers or (polications) is associated with important
advantages during transfection due to the possibility of electrostatic interactions
with DNA molecules [93, 95, 133]. This property together with the superparamagnetic behavior of IONPs make these nanostructures excellent adjuvants for DNA
vaccines. It has been reported that polymers bind with nucleic acid(s) to form complex structures known as polyplexes and that these polyplexes have increased transfection efficiency. Some of the examples reported in the literature include chitosan,
PEI, poly(2-hydroxyethyl methacrylate) (pHEMA), polyamidoamine (PAMAM)
dendrimers, polyethylene glycol (PEG), and poly-l-lysine [133, 145]. For example,
Al-Deen et al. reported the use of IONPs/PEI/DNA polyplexes to enhance the delivery of a malaria DNA vaccine using magnetofection [147]. Their results indicate that
in vitro transfection efficiency into eukaryotic cells can be significantly enhanced
under the application of an external magnetic field. Garu et al. also described a
novel DNA carrier based on lipoplexes of a model DNA vaccine using antibodylabeled MNPs [148]. This system revealed remarkable in vivo targeting properties
of the described liposomal DNA vaccine carrier. Importantly, mice immunization
induced a long-lasting anti-melanoma immune response.
4.3 Molecular Recognition Tools
One of the advantages of using MNPs in molecular platform technologies is related
to their easy manipulation due to a high separation efficiency with magnetic fields.
The principal disadvantage is related to the aggregation process that could occur
35
Reprinted from the journal
Topics in Current Chemistry (2020) 378:13
part of liposome formation [135]. Various examples of MNP applications in gene
delivery that have been reported in the literature are shown in Table 3.
Plasmids can be used not only as disease treatment, but also as a vaccination system for genetic immunization. A DNA vaccine is a third-generation vaccine that
incorporates a vector with a eukaryotic cell promoter and a gene that encodes for
an immunogenic protein. In contrast with protein-based traditional vaccines, DNA
vaccination has the capacity to induce both cellular and humoral immune responses.
The structure of plasmid DNA provides some advantages over other traditional
protein-based or carbohydrate-based vaccines since plasmid DNA can encode
many immunogenic proteins of the same virus and can also encode similar proteins
belonging to different infective agents [145]. Other important advantages of DNA
vaccines are their easy assembly, stability at room temperature, ease of manipulation, and low cost of plasmid production. However, the remaining challenges are to
increase transfection efficiencies and facilitate intracellular uptake and to improve
targeting to cells, as well as to perform these operations with small amounts of
DNA. Various gene delivery and adjuvant systems at the nanoscale are used to overcome these problems. During the use of a nanotechnological adjuvant, the degradation of DNA is prevented, resulting in ultra-rapid delivery by targeting to the desired
cells [146].
Adjuvants are generally grouped into two subtypes, namely, molecular adjuvants,
which are immunostimulants, and carrier structures, which are systems that control
release (e.g., mineral salts, liposomes, biodegradable polymers, and micro/nanoparticles). The use of cationic polymers or (polications) is associated with important
advantages during transfection due to the possibility of electrostatic interactions
with DNA molecules [93, 95, 133]. This property together with the superparamagnetic behavior of IONPs make these nanostructures excellent adjuvants for DNA
vaccines. It has been reported that polymers bind with nucleic acid(s) to form complex structures known as polyplexes and that these polyplexes have increased transfection efficiency. Some of the examples reported in the literature include chitosan,
PEI, poly(2-hydroxyethyl methacrylate) (pHEMA), polyamidoamine (PAMAM)
dendrimers, polyethylene glycol (PEG), and poly-l-lysine [133, 145]. For example,
Al-Deen et al. reported the use of IONPs/PEI/DNA polyplexes to enhance the delivery of a malaria DNA vaccine using magnetofection [147]. Their results indicate that
in vitro transfection efficiency into eukaryotic cells can be significantly enhanced
under the application of an external magnetic field. Garu et al. also described a
novel DNA carrier based on lipoplexes of a model DNA vaccine using antibodylabeled MNPs [148]. This system revealed remarkable in vivo targeting properties
of the described liposomal DNA vaccine carrier. Importantly, mice immunization
induced a long-lasting anti-melanoma immune response.
4.3 Molecular Recognition Tools
One of the advantages of using MNPs in molecular platform technologies is related
to their easy manipulation due to a high separation efficiency with magnetic fields.
The principal disadvantage is related to the aggregation process that could occur
35
Reprinted from the journal