Nanotechnology-enabled gene delivery for cancer and other genetic diseases

Abstract

Introduction: Despite gene therapy is ideal for genetic abnormality-related diseases, the easy degradation, poor targeting, and inefficiency in entering targeted cells are plaguing the effective delivery of gene therapy. Viral and non-viral vectors have been used for delivering gene therapeutics in vivo by safeguarding nucleic acid agents to target cells and to reach the specific intracellular location. A variety of nanotechnology-enabled safe and efficient systems have been successfully developed to improve the targeting ability for effective therapeutic delivery of genetic drugs.

Areas covered: In this review, we outline the multiple biological barriers associated with gene delivery process, and highlight recent advances to gene therapy strategy in vivo, including gene correction, gene silencing, gene activation and genome editing. We point out current developments and challenges exist of non-viral and viral vector systems in association with chemical and physical gene delivery technologies and their potential for the future.

Expert opinion: This review focuses on the opportunities and challenges to various gene therapy strategy, with specific emphasis on overcoming the challenges through the development of biocompatibility and smart gene vectors for potential clinical application.

Keywords: Gene therapy; drug delivery system; nanotechnology; non-viral vectors; viral vectors.

Figure 1.. Biological and physical barriers in vivo for precision medicine applications.

Summarization emphasizing several biological and physical barriers that nanomedicines can overcome (wathet) and what advantage that precision medicine applications could profit from nanomedicines (indipink). As this review probed, intelligent nanomedicines develop to enhance drugs delivery efficiency which means the potential to increase the performance of precision medicines further to accelerate the clinical translation. Reproduced with the permission, copyright@Springer Nature, 2020. doi.org/10.1038/s41573-020-0090-8. ^[25]

Figure 2.. Classes of Nucleic Acid Drug Delivery Carriers.

Each example of nanoparticle (NP) features multiple subclasses, with some of the most common highlighted here. Viral delivery carriers include RVs, LVs, ADVs, AAVs etc. and non-viral delivery carriers include polymeric systems (micelle, nanogel, linear chain, dendrimer, and polymersome, etc.), inorganic systems (Au/Ag NPs, quantum dots, and silica NPs, etc.), liposomal and exosome systems, DNA nanostructure-based, also some kinds of compounded nanomaterials the advantageous functions of different NPs combined. Each type has multitudinous vast merits and demerits regarding freight, delivery and disease responsiveness. Reproduced with the permission, copyright@John Wiley and Sons, 2020. doi.org/10.1002/adhm.202001238^[28]; copyright@Elsevier, 2018 doi.org/10.1016/j.tibtech.2018.01.006^[29].

Figure 3.

Au NVs for remote control of gene expression. Upon introducing a polymeric guest species specifically into cancer cells, the dissociated Au NRs functionalized with macrocyclic host molecules could re-aggregate rapidly in cells to retard exocytosis of these NRs. Reproduced with the permission, copyright@Chinese Chemical Society, 2022. doi.org/10.31635/ccschem.021.202101029^[60].

Figure 4.

Illustration of an siRNA-based vesicle (siRNAsome) formation and composition, which consists of a hydrophilic siRNA shell, a thermal- and intracellular-reduction-sensitive hydrophobic median layer, and an empty aqueous interior, for synergistic therapy in response to a reducing environment. T>LCST= Temperature greater than the lower critical solution temperature. Reproduced with the permission, copyright@ John Wiley and Sons, 2019. Doi.org/ 10.1002/anie.201814289^[101].

Figure 5.. Organ-tunable therapeutic gene modulation using engineered lipid nanoparticles.

SORT-LNPs are engineered by rapid mixing procedures. Reporter models based on luciferase expression and a Cre-Lox approach coupled to td-Tomato (tdTom) fluorescence were used to identify SORT-LNPs for tissue-specific gene expression and editing. hEPO, human erythropoietin; IL-10, interleukin 10. Reproduced with the permission, copyright@Springer Nature, 2020. doi.org/10.1038/s41565-020-0666-9.^[163]

Figure 6.. Scheme of the Preparation of gene editing nanostructures.

a) The preparation of CRISPR-Gold NPs. Gold nanoparticles were conjugated with a thiol-modified single stranded DNA (DNA-SH), and hybridized with single stranded donor DNA (SIZE=15 nm). Cas9 and gRNA are loaded and then a silicate and PASp(DET) polymer coating are added. b) Schematic illustration of MDNP formation and delivery process after intravenous injection, the average particle size of the CRISPR/dCas9 polyplex (N/P ratio = 30) = 150.2 ± 6.9 nm. Reproduced with the permission, copyright@Springer Nature, 2017. doi.org/10.1038/s41551-017-0137-2^[167]; copyright@John Wiley and Sons, 2019. doi.org/10.1002/advs.201801423^[166].