A Journey of Nanomotors for Targeted Cancer Therapy: Principles, Challenges, and a Critical Review of the State‐of‐the‐Art

Abstract

A nanomotor is a miniaturized device that converts energy stored in the environment into mechanical motion. The last two decades have witnessed a surge of research interests in the biomedical applications of nanomotors, but little clinical translation. To accelerate this process, targeted cancer therapy is used as an example to describe a “survive, locate, operate, and terminate” (SLOT) mission of a nanomotor, where it must 1) survive in the unfriendly in vivo environment, 2) locate its target as well as be located by human operators, 3) carry out specific operations, and 4) terminate after the mission is completed. Along this journey, the challenges presented to a nanomotor, including to power, navigate, steer, target, release, control, image, and communicate are discussed, and how state‐of‐the‐art nanomotors meet or fall short of these requirements is critically reviewed. These discussions are then condensed into a table for easy reference. In particular, it is argued that chemically powered nanomotors are intrinsically ill‐positioned for targeted cancer therapy, while nanomotors powered by magnetic fields or ultrasound show more promises. Following this argument, a tentative nanomotor design is then presented in the end to conform to the SLOT guideline, and to inspire practical, functional nanorobots that are yet to come.

Acoustically propelled nano- and microcones: fast forward and backward motion

“…Research on active nano-and microparticles is strongly motivated by their complex nonequilibrium behavior, which is interesting from a fundamental point of view, and by the wide range of possible future applications of such particles. [1][2][3][4] Among the most important potential fields of application are medicine [5][6][7][8][9][10][11][12] and materials science. [13][14][15][16][17][18][19] However, most of the active particles that have been developed so far are mainly useful for fundamental research but not suitable for applications, e.g., since their propulsion runs quickly out of fuel, requires a very particular chemical environment, or is not biocompatible.…”

Preparation of alginate hydrogel microparticles by gelation introducing cross-linkers using droplet-based microfluidics: a review of methods

“… Currently, most publications concern proof-of-concepts or preliminary demonstrations. Little work is available on microparticles in real biological or biomedical applications [ 53 ]. Apart from biological barriers [ 35 ], the physiological environment is quite complex in terms of composition and rheological characteristics, which makes it extremely unlikely that microparticles can provide the functions required.…”

Chemically Propelled Nano and Micromotors in the Body: Quo Vadis?

“…[32] Despite the early promise, however, the usefulness of active chemically powered nano and micromotors in diagnostics and treatment remains to be established. [33][34][35][36] They have yet to find a niche where such systems are indispensable or the tools of choice for a given application. What follows is our perspective on the critical barriers that must be overcome before the use of catalytic nano and micromotors in disease detection and treatment becomes acceptable (Figure 1).…”

“…[50] Still others move by bubble propulsion. [33][34][35][36] Again, these are unsuitable for introduction into the circulatory systems in the body for fear of embolism. More encouraging are the micromotors powered by enzyme catalysis, since they do not necessarily depend on the above propulsion mechanisms.…”