Gene Therapy in Cancer Treatment: Why Go Nano?

Abstract

The proposal of gene therapy to tackle cancer development has been instrumental for the development of novel approaches and strategies to fight this disease, but the efficacy of the proposed strategies has still fallen short of delivering the full potential of gene therapy in the clinic. Despite the plethora of gene modulation approaches, e.g., gene silencing, antisense therapy, RNA interference, gene and genome editing, finding a way to efficiently deliver these effectors to the desired cell and tissue has been a challenge. Nanomedicine has put forward several innovative platforms to overcome this obstacle. Most of these platforms rely on the application of nanoscale structures, with particular focus on nanoparticles. Herein, we review the current trends on the use of nanoparticles designed for cancer gene therapy, including inorganic, organic, or biological (e.g., exosomes) variants, in clinical development and their progress towards clinical applications.

Gold Nanoparticles for Vectorization of Nucleic Acids for Cancer Therapeutics

“…Some of these more precise approaches often include directing/targeting drugs directly at tumor cells via molecular actuators, antibodies and peptides that promote the destruction of cancer cells whilst sparing the surrounding healthy tissue (e.g., immune drug conjugates, gene therapy, etc.) [7].…”

“…Several types of nanosized vehicles have been developed for the vectorization of TNAs, such as polymeric particles, dendrimers, semiconductor quantum dots, amino acids, liposomes, carbon-based nanostructures, viral vectors, silica and metallic nanoparticles [7,76]. These vehicles are essential to deliver TNAs directed against cancer cells, even though the delivery efficiency of these carriers to malignant cells in clinical applications remains a challenge [76][77][78].…”

“…The paradigm is the enhanced permeability and retention (EPR) effect, which promotes the facilitated extravasation of NPs through the endothelia of surrounding vessels into the tumor. EPR occurs due to leaky endothelia resulting from the unstructured development and expansion of new vessels supplying the tumor with the greatly needed nutrients, which have grown too fast and without proper maturation to provide for fully structurally stable and finished architecture [7]. In the case of triggered targeting, NPs may release their content following a stimulus, such as a magnetic field (e.g., magnetic stimuli), an electric field, ultrasound or light (e.g., photothermy, optical hyperthermia) [83][84][85].…”

“…Metal nanoparticles, such as iron oxide (IONP), superparamagnetic iron oxide (SPION), silver (AgNP) and gold (AuNP), have been exhaustively used in several biomedical applications due to their physical and chemical properties, which are strongly dependent on size, shape, surface area, amphiphilicity and biocompatibility. Most of these NPs are often synthesized through simple procedures, and may be easily functionalized with a plethora of biomolecules, usually via simple chemistry (e.g., nucleic acids, proteins, drugs/compounds) to provide for biological activity and functionality [7,85,86].…”

“…For example, spherical AuNPs are good vectors for gene therapy, since they are easy to synthesize and usually exhibit low cytotoxicity, large specific surface areas that are easy to functionalize, high cell uptake and fast endosomal escape, making them biocompatible [7,29]. Due to some of the NPs' properties (surface charge, polarity, etc.…”