Nanoparticles in Medicine: Current Status in Cancer Treatment

Abstract

Cancer is still a leading cause of deaths worldwide, especially due to those cases diagnosed at late stages with metastases that are still considered untreatable and are managed in such a way that a lengthy chronic state is achieved. Nanotechnology has been acknowledged as one possible solution to improve existing cancer treatments, but also as an innovative approach to developing new therapeutic solutions that will lower systemic toxicity and increase targeted action on tumors and metastatic tumor cells. In particular, the nanoparticles studied in the context of cancer treatment include organic and inorganic particles whose role may often be expanded into diagnostic applications. Some of the best studied nanoparticles include metallic gold and silver nanoparticles, quantum dots, polymeric nanoparticles, carbon nanotubes and graphene, with diverse mechanisms of action such as, for example, the increased induction of reactive oxygen species, increased cellular uptake and functionalization properties for improved targeted delivery. Recently, novel nanoparticles for improved cancer cell targeting also include nanobubbles, which have already demonstrated increased localization of anticancer molecules in tumor tissues. In this review, we will accordingly present and discuss state-of-the-art nanoparticles and nano-formulations for cancer treatment and limitations for their application in a clinical setting.

Keywords: cancer treatment; carbon nanotubes; graphene; metallic nanoparticles; nanoparticles; polymeric nanoparticles; quantum dots.

Figure 1

Depictions of carbon nanomaterials: graphene hexagonal grid (A), fullerene C70 (B) and carbon nanotube (C). Carbon nanomaterials are structures made up of well-arranged sp2 carbon atoms and a nanoscale diameter with one or more walls or sheets. Figures provided by Wikimedia Commons and available under the Creative Commons CC0 License and Creative Commons Attribution-Share Alike 3.0.

Figure 2

Examples of polymers used for preparing polymer-based nanoparticles. Poly(lactic-co-glycolic) acid PLGA is a biocompatible synthetic polymer, while chitosan and fibroin are natural materials. Skeletal formula of chitosan—a linear polysaccharide composed of randomly distributed β-(1 → 4)-linked d-glucosamine (deacetylated unit) and N-acetyl-d-glucosamine (acetylated unit). This structure shows completely deacetylated chitosan. Figures provided by Wikimedia Commons and available under the Creative Commons CC0 License and Creative Commons Attribution-Share Alike 3.0. (A) Skeletal formula of poly(lactic-co-glycolic acid) (PLGA). Created using ACD/ChemSketch 10.0 and Inkscape. PLGA. (B) Silk fibroin primary structure. (C) Chitosan.

Figure 3

Schematic overview of tumor microenvironment and passive intratumor targeting of drug-carrying NPs. Due to the porous vessels, NPs can enter the vessels through passive diffusion and be delivered to the site of action in the tumor. This figure is similar those published before in studies by Cheng and Santos [135] and Roscigno et al. [136].

Figure 4

A schematic overview of active tumor cell targeting when the ligand on NPs carrying drug is a monoclonal antibody (MAb). When MAb binds with, in this case specifically, HER2 receptor on the tumor cell, it enters through the process of endocytosis. This enables NPs to release the drug that they are carrying inside the cell, which should lead to the apoptosis of the cell.

Figure 5

Schematic overview of current applications of NPs in medicine, which include cell imaging, in vivo imaging, drug delivery, gene delivery, cancer treatment and regenerative medicine.