Shaping cancer nanomedicine: the effect of particle shape on the in vivo journey of nanoparticles

Abstract

Recent advances in nanoparticle technology have enabled the fabrication of nanoparticle classes with unique sizes, shapes and materials, which in turn has facilitated major advancements in the field of nanomedicine. More specifically, in the last decade, nanoscientists have recognized that nanomedicine exhibits a highly engineerable nature that makes it a mainstream scientific discipline that is governed by its own distinctive principles in terms of interactions with cells and intravascular, transvascular and interstitial transport. This review focuses on the recent developments and understanding of the relationship between the shape of a nanoparticle and its navigation through different biological processes. It also seeks to illustrate that the shape of a nanoparticle can govern its in vivo journey and destination, dictating its biodistribution, intravascular and transvascular transport, and, ultimately, targeting of difficult to reach cancer sites.

Figure 1. Schematic of biological processes which influence nanoparticle delivery

A nanoparticle must be able to circulate, marginate, and bind to a vascular target or extravasate into the tumor interstitium before it can be internalized by a cancer cell.

Figure 2. Effect of contact angle (θ) on the rate of nanoparticle internalization

Rod-shaped nanoparticles internalize most quickly when their major axis is perpendicular to the cell membrane. As the rod is oriented more tangentially to the cell membrane, the rate of internalization decreases. This is due to the increased difficulty to “wrap” the nanoparticle. Because spherical nanoparticles are symmetric, they internalize at a rate independent of θ.

Figure 3. Effect of shape on nanoparticle margination

Spherical nanoparticles tend to remain in the center of the flow. Variable forces and torques exerted on rods under flow allow them to marginate and drift towards the vessel wall, where they are able to bind to wall receptors or extravasate through gaps between cells of the endothelium.

Figure 4. Effect of shape on nanoparticle binding avidity

Shape, ligand length, and polymer flexibility all play a role in the active fractional area of a nano-carrier (AFAC). For a sphere, the AFAC is defined as (L-d_B)/D_c, where L is the length of the ligand, d_b is the binding distance between the nanoparticle and the receptor, and D_c is the diameter of the nano-carrier. For particles with equal surface area, the ligand length, binding distance, and shape affects AFAC.