Nanoparticles in Gene Delivery and Theranostics
Abstract
Nanoparticles (NPs) are recently gaining significant attention as efficient non-viral gene delivery vehicles and theranostic multifunctional platforms to overcome the main drawbacks of gene therapy, such as enzymatic degradation, suboptimal cellular uptake, endosomal trapping, and off-target side effects. This chapter describes the basic principles of gene delivery with a focus on different types of nucleic acid cargos (plasmid DNA, mRNA, siRNA, miRNA and CRISPR/Cas9), and the comparison of viral and non-viral delivery methods. The systematic classification of NPs is presented, including lipid-based systems (liposomes, solid lipid nanoparticles, nanostructured lipid carriers), polymeric nanocarriers (chitosan, PLGA, dendrimers, polyethyleneimine), inorganic nanoparticles (gold, silver, mesoporous silica, superparamagnetic iron oxide), and carbon-based nanomaterials (carbon nanotubes, graphene oxide, fullerenes). Special focus is given to their physicochemical properties (shape, size, surface charge, functionalization), the mechanisms of their nucleic acid encapsulation, their endocytic uptake pathways, endosomal escape, their intracellular trafficking, nuclear localization, and their stimuli-responsive release. Theranostics is explored in the context of co-delivering therapeutic genes with imaging probes (MRI, CT, fluorescence, PET/SPECT) for image-guided targeted gene silencing, combinatorial chemo-gene therapy, photothermal and photodynamic therapy, and personalised oncology. Passive (EPR effect) and active targeting, as well as pH-, redox-, enzyme- and thermo-responsive systems are critically reviewed. Safety considerations such as nanotoxicology, biocompatibility, immunogenicity, biodistribution, clearance, and regulatory frameworks and ethical implications are discussed. Translational advances and challenges in scalability and commercialization are highlighted by FDA-approved nanomedicines (e.g. Onpattro) and current clinical trials.
Author Affiliations
- 1 Assistant Professor, Department of Pharmaceutical Chemistry, SBSPM's B. Pharmacy College, Ambajogai, Maharashtra, India.
- 2 Assistant Professor, Shri Bhairavnath Nisarg Mandal's Diploma Institute of Pharmacy, Hatta, Hingoli, Maharashtra, India.
- 3 Principal, SVERI College of Pharmacy, Pandharpur, Maharashtra, India.