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The applications of gene therapy in approaching the target disease by genetic material engineered modification or substitution at the site of gene expression in the target cells are vectored by the nanotools [28]. The advances in nanoparticles as an emerging technique are a promising tool for clinical therapy utilizing their nature of shape, size, surface, biological deportment, and properties. Gene-based therapy is showcased as an emerging advanced significant strategy for the treatment of many diseases associating the specific gene responsible for the following diseases: tumors, neurodegenerative diseases, autoimmune disease, hypercholesterolemia, hemophilia, many microbial caused diseases, etc. The strategy involves introducing a gene into a particular target pathogen tissue causing modification or substitution at the endogenous gene expression by employing nanoparticle dosage form as a vehicle for delivery, preventing and curing the progression of that disease. The major challenges of this particular delivery of genomic material to the target site by equipping nanotech are the encapsulation efficacy of the genomic material in the nanodosage form, degradation in systemic circulation, endocytosis and endosomal escape by the target tissues, efficacy of the delivery system, pharmacological toxicity, and nanoparticle stability [29]. To bypass these many hinders, there are researchers forecasting many different types of nanocarriers for genetic material delivery such as lipoid-based nanoformulations, polymeric nanoparticles, and inorganic nanovehicles [30]. In 2016, Farris et al. developed and formulated a clinical nanocarrier for delivering a gene. A multinucleotide vaccine synthesizes a protein antigen in the area neighboring the antigen presenting cell leading to immunological responses. The key components (DNA) of the formulated vaccine delivery system can economically produce and has better storage and handling property than the components present in the other major peptide-based vaccines [31].

Various types of nanoformulations (Table 3.1) as carriers opting the advantage of their morphology, function, and composition are mentioned below:

Table 3.1 An overview of the nanotools.

Customized nanotools	Size range (nm)	Description	Advantages	Disadvantages
Liposomes	50 to 100	A spherical vesicle containing minimum of one lipid bilayer encapsulating the aqueous core contain the drug molecules serve as a carrier.	Increase the efficacy and therapeutic index of the drugReduce toxicityFlexibility to couple to the target specific ligandsBiocompatible, biodegradable, non-immunogenic for both systemic and nonsystemic administration	Low solubilityLesser half-lifeLipids undergo reactions like oxidation and hydrolysis to a specific extentLeakage and fusion of the vesiclesEconomically high in costLess stable
Solid lipid nanoparticle (SLN)	50 to 1000	Globular structure vesicles encapsulated by monolayers of phospholipids containing dissolved or dispersed drug in the core media.	Control and/or target drug release and enhance bioavailabilityExcellent biocompatibilityHigh and enhanced drug contentEasy to scale up and sterilizeBetter control over release kinetics of encapsulated compoundsLiable drugsChemical protection of labile incorporated compoundsCan be subjected to commercial sterilization procedures.	Particle growthUnpredictable gelation tendencyUnexpected dynamics of polymeric transitions.
Nanocarbon tubes	20 to 1000	They are cylindrical molecules consisting of multilayers of rolled-up sheets of carbon atoms.	High bioavailability because of its high specific surface area and nanosize range.Multiple conjugation sites for the drug molecule.	Lack of solubility in aqueous media
Polymer-based nanoparticles	10 to 1000	Colloidal particles comprising drugs encapsulated or impinged by polymeric substance.	Increase the stability of volatile drug substance Biodegradable, biocompatible, and non-immunogenic Site-specific targeted drug delivery Reduce the adverse drug reactions	Toxic monomer aggregation Polymeric degradation On degradation, they yield toxic residual material
Polymer-based micelles	10 to 100	Self-assembled nanoscopic core shell formed by amphiphilic copolymer, containing hydrophobic drugs surrounded by micelles and hydrophilic bioactive materials.	Serves the advantage of controlled drug release NontoxicHigher physical stability Greater cargo capacity of drugs	Poor drug loading efficiency.Poor in vivo stability Poor cellular interaction with malignant tissues
Dendrimers	< 10	Branched molecules that consist of a core and spherical 3D morphology.	Low toxic and antigenic.Biodegradable and metabolized.Can increase the half-life of the moiety.Good tissue permeability.Aids sustained and controlled drug release.	Limited storage condition.Time consuming.High material and equipment cost.Low retention.More complex in nature.
Metallic nanoparticles	< 100	They are nanosized metals that are synthesized and modified to bind along with ligands, antibodies, drugs, etc.	Optical properties like photo absorption, light scattering, modified SERS (surface enhanced Raman scattering) and fluorescenceEnhance the resolutions of the imaging techniques such as MRI, tracking stem cells, and cellular molecules.	They are concerned with the issues of high toxicity.Their shape, size, surface chemistry, targeting ligands, elasticity, and composition largely influence their toxic profile.High in material and production cost.
Quantum dots	2 to 10	They are smaller nano range tiny nanoparticles and have good optical and electronic properties that vary from larger particles due to their intrinsic quantum mechanics.	They are better than fluorophore dyes that are 20 times brighter.Variations in the wavelength ranging from 400 to 4000 nm range.They are economically cost effective and also amenable to high-speed printing techniques.	Highly toxic and require stable polymer shell.The shells can alter the optical property.Hard to control the particle size of the nano structures.DegradationOverall conversion yield is poor.
Nanodiamonds	~5	Medically used diamonds of size range lesser than 5 nm containing three main components: the core, surface, and the overall shape.	They can be used in the drug delivery in their original form whereas there is no need to apply the oxidation modification process due to their good aqueous solubility nature, without any acidic media treatment.Reduces adverse effects.High affinity towards proteins and antibodies forming stable conjugates	Chances of genotoxicity occurrence due to the introduction of various chemical groups into the nanodiamonds.Difficulties in evaluation due to being smaller in size; special techniques such as radionuclide tracer are to be adopted.The process is quite complicated during the complexation of nanodiamonds with the active drug molecules covalently.Economically high in cost.