Clinical Cancer Nanomedicine

Abstract

Nanotechnology offers new solutions for the development of cancer therapeutics that display improved efficacy and safety. Although several nanotherapeutics have received clinical approval, the most promising nanotechnology applications for patients still lie ahead. Nanoparticles display unique transport, biological, optical, magnetic, electronic, and thermal properties that are not apparent on the molecular or macroscale, and can be utilized for therapeutic purposes. These characteristics arise because nanoparticles are in the same size range as the wavelength of light and display large surface area to volume ratios. The large size of nanoparticles compared to conventional chemotherapeutic agents or biological macromolecule drugs also enables incorporation of several supportive components in addition to active pharmaceutical ingredients. These components can facilitate solubilization, protection from degradation, sustained release, immunoevasion, tissue penetration, imaging, targeting, and triggered activation. Nanoparticles are also processed differently in the body compared to conventional drugs. Specifically, nanoparticles display unique hemodynamic properties and biodistribution profiles. Notably, the interactions that occur at the bio-nano interface can be exploited for improved drug delivery. This review discusses successful clinically approved cancer nanodrugs as well as promising candidates in the pipeline. These nanotherapeutics are categorized according to whether they predominantly exploit multifunctionality, unique electromagnetic properties, or distinct transport characteristics in the body. Moreover, future directions in nanomedicine such as companion diagnostics, strategies for modifying the microenvironment, spatiotemporal nanoparticle transitions, and the use of extracellular vesicles for drug delivery are also explored.

Keywords: drug delivery; extracellular vesicle; multifunctional; nanomedicine; nanoparticle.

Figure 1 |. Multifunctional properties of nanotherapeutics.

Figure 2 |. Hemodynamic-based tumor targeting.

Spherical nanoparticles follow the streamline (upper panel), while discoidal microparticles flow close to the vessel wall (lower panel). Proximity to the endothelium and a large parallel surface area that can attach to the vessel wall make disc-shaped particles ideal for vascular adhesion. Unique hemodynamics in normal and tumor blood vessels lead to different patterns of particle adhesion. Specifically, the disorganized vasculature network of tumors leads to lower shear rates and permanent attachment of discoidal microparticles