The emergence of nanotechnology has revolutionized several sectors, and healthcare is no exception. Among its many applications, nanotechnology’s potential for targeted drug delivery is particularly promising. In this review, we will focus on the development of nanobots in cancer therapy, encapsulating the core principles of their operation and the most recent advances in their design and application.
Introduction
Cancer remains a leading cause of mortality worldwide. Although considerable progress has been made in cancer therapy, current treatments often fail to distinguish between healthy and cancerous cells, leading to significant off-target effects. However, the advent of nanotechnology presents an innovative and potentially transformative solution to this challenge: nanobots.
Nanobots, nanoscale robots capable of performing specific tasks, are becoming increasingly viable as tools for targeted cancer therapy. These nanoscale systems can be engineered to recognize cancer cells, deliver drugs or therapeutic payloads directly to these cells, and subsequently reduce the impact on healthy tissues. This approach opens up exciting avenues for improving the therapeutic index of anticancer treatments, minimizing side effects, and enhancing patient quality of life.
DNA Origami Nanorobots
The burgeoning field of DNA nanotechnology has led to the development of DNA origami nanorobots, constructed from folded DNA strands. In a groundbreaking study published in “Nature Biotechnology”, researchers demonstrated the potential of DNA origami nanorobots to target cancerous tumors and deliver thrombin, an enzyme that can induce tumor death by blocking its blood supply.
The nanorobots were designed to open and release their payload in response to a protein called nucleolin, which is overexpressed on the surface of cancer cells. In mouse models of breast cancer, melanoma, ovarian and lung cancers, the nanorobots successfully delivered thrombin to tumors, leading to tumor necrosis and inhibition of tumor growth, without affecting healthy tissues [1].
Biomimetic Nanosystems
Biomimetics, the imitation of models, systems, and elements of nature, has provided inspiration for designing sophisticated nanobots. A notable example is the development of neutrophil nanosponges, essentially nanoparticles coated with neutrophil cell membranes. Neutrophils, a type of white blood cell, are naturally capable of migrating towards inflammatory signals, making them ideal for targeting inflammation-promoting cancer cells.
The neutrophil nanosponges were shown to absorb pro-inflammatory cytokines released by tumor cells, reducing inflammation and inhibiting tumor growth. In mouse models of melanoma and lung cancer, these nanosponges effectively decreased tumor growth [2].
Magnetic Nanoparticles
Another promising approach involves the use of magnetic nanoparticles. When exposed to an alternating magnetic field, these nanoparticles generate heat, a technique known as magnetic hyperthermia, which can kill cancer cells.
Researchers have coated magnetic nanoparticles with a biocompatible polymer and a targeting molecule that binds to a protein overexpressed in breast cancer cells. The targeted nanoparticles accumulated in the tumors and, when exposed to an alternating magnetic field, successfully killed the cancer cells [3].
Challenges and Future Perspectives
While the potential of nanobots in cancer therapy is enormous, significant challenges lie ahead. These include potential off-target effects and toxicity, large-scale manufacturing, and navigating the regulatory landscape.
Furthermore, the complexities of the tumor microenvironment, such as the heterogeneity of cancer cells and the dynamics of tumor-host interactions, pose additional challenges for the design and operation of nanobots. Future research must address these issues to translate the potential of nanobots into clinical reality.
Nonetheless, nanobots represent a novel and promising approach in cancer therapy. Their ability to target cancer cells, deliver therapeutic payloads, and reduce off-target effects holds immense promise for improving the therapeutic outcomes of cancer patients. As our understanding of nanotechnology and cancer biology deepens, we anticipate the emergence of increasingly sophisticated nanobots capable of ever more precise and effective cancer targeting.
References
- Li, S. et al. A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo. Nature Biotechnology 36, 258-264 (2018).
- Zhang, Q. et al. Neutrophil membrane-coated nanoparticles inhibit synovial inflammation and alleviate joint damage in inflammatory arthritis. Nature Nanotechnology 13, 1182–1190 (2018).
- Zhao, Z. et al. Octapod iron oxide nanoparticles as high-performance T2 contrast agents for magnetic resonance imaging. Nature Communications 4, 2266 (2013).