From Diagnosis to Treatment: Clinical Applications of Nanotechnology in Thoracic Surgery

Abstract

Nanotechnology is an emerging field with potential as an adjunct to cancer therapy, particularly thoracic surgery. Therapy can be delivered to tumors in a more targeted fashion, with less systemic toxicity. Nanoparticles may aid in diagnosis, preoperative characterization, and intraoperative localization of thoracic tumors and their lymphatics. Focused research into nanotechnology's ability to deliver both diagnostics and therapeutics has led to the development of nanotheranostics, which promises to improve the treatment of thoracic malignancies through enhanced tumor targeting, controlled drug delivery, and therapeutic monitoring. This article reviews nanoplatforms, their unique properties, and the potential for clinical application in thoracic surgery.

Keywords: Lung cancer; Nanotechnology; Nanotheranostics; Thoracic surgery.

Figure 1

Nanoplatforms display distinct advantages and disadvantages.

Figure 2

Tumor targeting of nanoparticles. A. Permeable vasculature from endothelial cell gaps leads to passive diffusion of small molecules and nanocarriers into the tumor microenvironment. Due to their size, nanocarriers do not diffuse out as easily and hence accumulate within the tumor tissue. B. Specific receptors on nanocarriers target ligands on the tumor tissue. From Danhier F, Oliver F, Veronique P. To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. 2010;148(2):135–146; with permission.

Figure 3

Nanoparticles participate in each step from diagnosis of cancer to the various forms of treatment. Nanoparticles can be engineered to function at multiple different steps and in combination with each other.

Figure 4

Stimuli-responsive nanoparticles. A variety of endogenous and exogenous stimuli can induce a specific action or release of drug.

Figure 5

pH responsive expansile nanoparticles (eNP) expand to release drug when in the presence of a pH of 5. Adapted from Stolzoff M, Ekladious I, Colby AH, et al. Synthesis and Characterization of Hybrid Polymer/Lipid Expansile Nanoparticles: Imparting Surface Functionality for Targeting and Stability. Biomacromolecules. 2015;16(7):1958-66; with permission.

Figure 6

NIR-labeled redox-sensitive nanoparticles reproducibly concentrate in tumor over time. From Nguyen CT, Tran TH, Amiji M, et al. Redox-Sensitive Nanoparticles from amphiphilic cholesterol-based block copolymers for enhanced tumor intracellular release of doxorubicin. Nanomedicine. 2015. [Epub ahead of print]; with permission.

Figure 7

siRNA can be introduced via nanocarrier or double stranded DNA that is cleaved by the Dicer enzyme within the cell. The siRNA is then incorporated into the RNA-induced silencing complex (RISC) leading to cleavage of target mRNA and thus silencing of the targeted gene. From Whitehead KA, Langer R, Anderson DR. Knocking down barriers: advances in siRNA delivery). Macmillan Publishers Ltd: Nature Reviews Drug Discovery 2009;8(2):129-38; with permission.

Figure 8

Nanotheranositics. These agents combine many properties of the basic nanoparticles to form single platforms capable of both diagnostics and therapeutics.