**6.1. Magnetic nanoparticle**

Combination of inorganic nanoparticles with organic materials forms hybrids which possess unique physical, chemical, optical, and electrical properties. These unique properties can be utilized in different applications than large size materials. Recently, magnetic nanoparticles have been utilized as an effective tool in gene delivery because of its submicron size. Hence, much research has been carried out to control the size and shape of the metal nanostructure due to its magnetic, catalytic, electrical, and optical properties. Iron oxides, such as CoFe2O4, NiFe2O4, and MnFe2O4, exhibit superior performance compared to other magnetic materials but highly toxic to cells. The most widely used iron oxide as magnetic cores are magnetite (Fe3O4) and maghemite (γ-Fe2O3), possess high magnetic moments and relatively safe. The magnetic nanoparticle core is fairly reactive, prevents corrosion and leaking when applied *in vivo*. In the magnetic nanoparticle gene delivery system, the gene directly binds to the magnetic particle or carrier. In magnetic nanoparticle, a magnetic core is coated by a protective layer either by dispersing in a polymer matrix or encapsulated within a polymer/metallic shell, which can be combined with therapeutic agents (carrier/DNA complexes or other drugs) through covalent or noncovalent bond. Silica, gold, natural polymers, such as dextran, or synthetic polymers, such as PEI, PLL, PEG, and polyvinyl alcohol (PVA), are commonly used coating materials in magnetic nanoparticle. Introduction of various functional groups (organic linkers) like carboxyl, amines, thiols, and aldehyde can alter the surface properties to suit various therapeutic agents to improve targeted gene delivery. The preferred coating surface for magnetic particles is strongly cationic because of the negatively charged DNA molecules that are to be delivered. Magnetofection is a methodology based on the association of magnetic nanoparticle with gene vectors in order to optimize/enhance gene delivery in the presence of a magnetic field. The magnetic field is applied to move the MNP-gene vector complexes toward the target site. In magnetofection, gene can be delivered in few minutes to the target site, whereas traditional transfection methods can take several hours. Stability of any magnetic nanoparticles depends upon the balance between attractive (van der Waals and dipole-dipole) and repulsive (steric and electrostatic) forces between the particles and the surrounding solvent molecules. Temperature also has an effect in the stability of the magnetic nanoparticle due to energy transfer from the solvent molecules (Brownian motion) to the nanometric particles. Hence, magnetic nanoparticle can be coated with a biocompatible polymer to enhance its stability [30, 31, 48–62].

## **6.2. Metal nanoparticle (gold nanoparticle)**

**5. Nonviral vector gene delivery**

18 Advanced Technology for Delivering Therapeutics

transferring of a gene into a target cell [41–44].

nanotubes, gold nanoparticles (GNPs), etc.) [45].

**•** They exist in the same size domain as proteins.

**6. Inorganic type nonviral delivery vectors**

gold nanoparticles, and so on [31, 47].

reasons.

groups.

characteristics. [46].

**6.1. Magnetic nanoparticle**

Nonviral vector consists of either natural vectors (plasmid DNA or small nucleic acids, antisense oligonucleotides, small interfering RNAs) or synthetic vectors (liposomes, cationic polymers) [40]. Naked DNA, usually in plasmid form, is the simplest form of non-viral

Nonviral vector delivery is categorized as organic (lipid complexes, conjugated polymers, cationic polymers, etc.) and inorganic systems (magnetic nanoparticles, quantum dots, carbon

To achieve the desired therapeutic efficacy, a suitable carrier system is needed. Nanoparticles can be considered as a good carrier for various therapeutic applications due to the following

**•** They have large surface areas and ability to bind to a large number of surface functional

**•** They possess controllable absorption and release properties and particle size and surface

Inorganic type of nonviral delivery vectors are magnetic nanoparticles, quantum dots, and

Combination of inorganic nanoparticles with organic materials forms hybrids which possess unique physical, chemical, optical, and electrical properties. These unique properties can be utilized in different applications than large size materials. Recently, magnetic nanoparticles have been utilized as an effective tool in gene delivery because of its submicron size. Hence, much research has been carried out to control the size and shape of the metal nanostructure due to its magnetic, catalytic, electrical, and optical properties. Iron oxides, such as CoFe2O4, NiFe2O4, and MnFe2O4, exhibit superior performance compared to other magnetic materials but highly toxic to cells. The most widely used iron oxide as magnetic cores are magnetite (Fe3O4) and maghemite (γ-Fe2O3), possess high magnetic moments and relatively safe. The magnetic nanoparticle core is fairly reactive, prevents corrosion and leaking when applied *in vivo*. In the magnetic nanoparticle gene delivery system, the gene directly binds to the magnetic particle or carrier. In magnetic nanoparticle, a magnetic core is coated by a protective layer either by dispersing in a polymer matrix or encapsulated within a polymer/metallic shell, which can be combined with therapeutic agents (carrier/DNA complexes or other drugs) through covalent or noncovalent bond. Silica, gold, natural polymers, such as dextran, or Owing to nano-dimension size to volume ratio and its stability, inorganic (metal) nanoparticles are being extensively used as promising gene carriers in various biomedical applications. Among the various metal nanoparticle gold nanoparticles (GNPs) are an obvious choice due to its inert, amenability of synthesis, high functionalization, fictionalization ability, higher absorption coefficient, good biocompatibility, less cytotoxic, ease of detection, and potential capability of targeted delivery, hence it is extensively used for various applications including drug and gene delivery. Due to its remarkable stability, large surface area, surface modification, and high biocompatibility, gold nanoparticles can retain the native structure and enzymatic activity of the attached proteins or enzymes in the drug delivery. Gold nanoparticles have large surface area due to which their surfaces are readily available for modification with targeting molecules or specific biomarkers and applicable in biomedical purposes.

Gold nanoparticles have large surface bio conjugation with molecular probes, and they also have many optical properties which are mainly concerned with localized plasmon resonance (PR). Gold nanoparticles can bind with a wide range of organic molecules and have tunable physical and chemical properties. Gold nanoparticles can be synthesized by chemical (seeding growth method), physical (γ-irradiation method, microwave irradiation method), and green methods (natural biomaterial egg shell membrane, sun light irradiation method).

Combination of gold nanoparticles into smart polymer like poly (N-isopropylacrylamine) is an effective process to enhance its properties. Gold nanoparticles exhibit different shapes such as spherical, sub-octahedral, octahedral, decahedral, icosahedral multiple twined, multiple twined, irregular shape, tetrahedral, nanotriangles, nanoprisms, hexagonal platelets, and nanorods, which are shown in **Figure 2**. Among the various shapes triangular-shaped nanoparticles show attractive optical properties compared with the spherical-shaped nanoparticles [30, 58, 63–72].

**Figure 2.** Various shapes of gold nanoparticle.
