Nanoparticle strategies for cancer therapeutics: Nucleic acids, polyamines, bovine serum amine oxidase and iron oxide nanoparticles (Review)

Abstract

Nanotechnology for cancer gene therapy is an emerging field. Nucleic acids, polyamine analogues and cytotoxic products of polyamine oxidation, generated in situ by an enzyme-catalyzed reaction, can be developed for nanotechnology-based cancer therapeutics with reduced systemic toxicity and improved therapeutic efficacy. Nucleic acid-based gene therapy approaches depend on the compaction of DNA/RNA to nanoparticles and polyamine analogues are excellent agents for the condensation of nucleic acids to nanoparticles. Polyamines and amine oxidases are found in higher levels in tumours compared to that of normal tissues. Therefore, the metabolism of polyamines spermidine and spermine, and their diamine precursor, putrescine, can be targets for antineoplastic therapy since these naturally occurring alkylamines are essential for normal mammalian cell growth. Intracellular polyamine concentrations are maintained at a cell type-specific set point through the coordinated and highly regulated interplay between biosynthesis, transport, and catabolism. In particular, polyamine catabolism involves copper-containing amine oxidases. Several studies showed an important role of these enzymes in developmental and disease-related processes in animals through the control of polyamine homeostasis in response to normal cellular signals, drug treatment, and environmental and/or cellular stress. The production of toxic aldehydes and reactive oxygen species (ROS), H2O2 in particular, by these oxidases suggests a mechanism by which amine oxidases can be exploited as antineoplastic drug targets. The combination of bovine serum amine oxidase (BSAO) and polyamines prevents tumour growth, particularly well if the enzyme has been conjugated with a biocompatible hydrogel polymer. The findings described herein suggest that enzymatically formed cytotoxic agents activate stress signal transduction pathways, leading to apoptotic cell death. Consequently, superparamagnetic nanoparticles or other advanced nanosystem based on directed nucleic acid assemblies, polyamine-induced DNA condensation, and bovine serum amine oxidase may be proposed for futuristic anticancer therapy utilizing nucleic acids, polyamines and BSAO. BSAO based nanoparticles can be employed for the generation of cytotoxic polyamine metabolites.

The antioxidant, aged garlic extract, exerts cytotoxic effects on wild-type and multidrug-resistant human cancer cells by altering mitochondrial permeability

“…Nanoparticlebased therapies have been shown to reduce systemic toxicities and to enhance therapeutic efficacy of drugs (60,61). Our research group has previously performed several studies into the research of novel nanoparticles in inducing polyamine and bovine serum amine oxidase (BSAO)-based nanoparticles to overcome some of the issues associated with conventional anticancer therapy, including the limitations of treating drug resistant tumors (62). To increase the stability of the enzyme and the release of cytotoxic products, core-shell gold nanoparticles have been employed for the immobilization of BSAO (63).…”

Polyamine catabolism and oxidative damage

“…Experiments in multidrug-resistant tumor cell lines have indicated their increased sensitivity to the oxidation products of BSAO and Spm (113)(114)(115)(116). Recent advances in drug delivery technology have led to the incorporation of BSAO into nanoparticle formulations, thereby enhancing the stability of its catalytic activity and improving its potential as an in situ treatment strategy to reduce intratumoral PA levels while generating tumor-toxic oxidative stress (117)(118)(119).…”

Multimodal correlative microscopy for in situ detection and quantification of chemical elements in biological specimens. Applications to nanotoxicology

“…NPs have unique physicochemical properties such as large surface area per gram, high surface/volume ratio, surface reactivity, charge, and shape, which make them extensively used in industry. As their size approaches that of proteins, DNA, and other biological species, they are used in bioapplications such as therapeutics [1], antimicrobial agents [19], transfection vectors [8,6], and for fluorescent labeling [14,9]. Nevertheless, besides the numerous physical and chemical advantages exhibited by NPs, the risks for adverse health effects due to prolonged or repetitive exposures at various concentration levels in biological species and in the environment have not yet been clearly established.…”