Nanoparticles for death‑induced gene therapy in cancer (Review)

Abstract

Due to the high toxicity and side effects of the use of traditional chemotherapy in cancer, scientists are working on the development of alternative therapeutic technologies. An example of this is the use of death‑induced gene therapy. This therapy consists of the killing of tumor cells via transfection with plasmid DNA (pDNA) that contains a gene which produces a protein that results in the apoptosis of cancerous cells. The cell death is caused by the direct activation of apoptosis (apoptosis‑induced gene therapy) or by the protein toxic effects (toxin‑induced gene therapy). The introduction of pDNA into the tumor cells has been a challenge for the development of this therapy. The most recent implementation of gene vectors is the use of polymeric or inorganic nanoparticles, which have biological and physicochemical properties (shape, size, surface charge, water interaction and biodegradation rate) that allow them to carry the pDNA into the tumor cell. Furthermore, nanoparticles may be functionalized with specific molecules for the recognition of molecular markers on the surface of tumor cells. The binding between the nanoparticle and the tumor cell induces specific endocytosis, avoiding toxicity in healthy cells. Currently, there are no clinical protocols approved for the use of nanoparticles in death‑induced gene therapy. There are still various challenges in the design of the perfect transfection vector, however nanoparticles have been demonstrated to be a suitable candidate. This review describes the role of nanoparticles used for pDNA transfection and key aspects for their use in death‑induced gene therapy.

Magnetite Nanoparticles Coated with PEG 3350-Tween 80: In Vitro Characterization Using Primary Cell Cultures

“…Nanoparticles with a diameter smaller than 5.5 nm results in a rapid urinary excretion [41]. A disadvantage of larger particles is that they are easily recognized by the macrophages from the immune system, while smaller sizes have a longer circulation time in blood [4]. In fact, agglomeration of coated nanoparticles is demonstrated in DLS results, but SEM images shows well defined nanoparticles in the nanometer scale.…”

“…There was a difference between bare magnetite nanoparticles, which were non-hemolytic at the concentration of 1000 µg/mL, against nanoparticles coated with PEG 3350-Tween 80, which were high hemolytic at the same concentration. This grade of hemotoxicity can be attributed to the positive charges in the coated nanoparticle surface [4].…”

“…There was a difference between bare magnetite nanoparticles, which were non-hemolytic at the concentration of 1000 µg/mL, against nanoparticles coated with PEG 3350-Tween 80, which were high hemolytic at the same concentration. This grade of hemotoxicity can be attributed to the positive charges in the coated nanoparticle surface [4]. Although there are many advantages of the use of PEG 3350 and Tween 80, such as prolonging the circulation time in the body [12], the correct formulations and concentrations in the use of the coating must be measured and tested because excess of coating can cause several problems at the cellular level.…”

“…MNPs must be designed taking into consideration their physical characteristics to be biocompatible with blood elements and not cause cytotoxicity to other tissues. Nanoparticle size should be from 30 to 150 nm because nanoparticles with smaller sizes are immediately discarded from the blood by the kidneys and large sizes hardly cross biological barriers like epithelia [4]. Due to these characteristics, MNPs have a potential to be applied as an alternative in the diagnosis or treatment of several diseases, such as cancer.…”

“…However, a common problem with some polymeric nanoparticles in blood is their high surface charge, which can interact with erythrocytes causing lysis. Polyethylene glycol (PEG) is a nontoxic and non-electrostatic-charge linear polymer [4] that has already been used to coat MNPs. Although there is a common use of PEG in medicine [10,11], the interaction of the PEG molecule with the human body is still being studied [12][13][14].…”