Nanotechnology applications in thoracic surgery

Abstract

Nanotechnology is an emerging, rapidly evolving field with the potential to significantly impact care across the full spectrum of cancer therapy. Of note, several recent nanotechnological advances show particular promise to improve outcomes for thoracic surgical patients. A variety of nanotechnologies are described that offer possible solutions to existing challenges encountered in the detection, diagnosis and treatment of lung cancer. Nanotechnology-based imaging platforms have the ability to improve the surgical care of patients with thoracic malignancies through technological advances in intraoperative tumour localization, lymph node mapping and accuracy of tumour resection. Moreover, nanotechnology is poised to revolutionize adjuvant lung cancer therapy. Common chemotherapeutic drugs, such as paclitaxel, docetaxel and doxorubicin, are being formulated using various nanotechnologies to improve drug delivery, whereas nanoparticle (NP)-based imaging technologies can monitor the tumour microenvironment and facilitate molecularly targeted lung cancer therapy. Although early nanotechnology-based delivery systems show promise, the next frontier in lung cancer therapy is the development of 'theranostic' multifunctional NPs capable of integrating diagnosis, drug monitoring, tumour targeting and controlled drug release into various unifying platforms. This article provides an overview of key existing and emerging nanotechnology platforms that may find clinical application in thoracic surgery in the near future.

Keywords: Drug delivery; Imaging; Lung cancer; Nanoparticles; Nanotechnology; Theranostics.

Figure 1:

Lymphatic mapping of a porcine lung utilizing NIR fluorescent QD technology. Representative NIR fluorescence images depicted from top to bottom of the surgical field over the following timepoints: (i) pre QD injection (autofluorescence), (ii) time of QD injection, (iii) 45 s post QD injection (lung retracted), (iv) 1 min post QD injection, (v) post sentinel lymph node resection. For each timepoint, colour video (left), NIR fluorescence (middle) and colour-NIR (right) images are demonstrated. White arrow indicates rapid QD localization to the SLN. Absence of fluorescence in the nodal basin after resection confirms complete removal of the sentinel nodal tissue (Reprinted from ref. [15], with permission from Elsevier, Fig. 2A). NIR: near-infrared; QD: quantum dot; SLN: sentinel lymph node.

Figure 2:

Schematic illustration of image-guided surgery using triple-modality MPR nanoparticle. Top: MPRs are injected intravenously into a mouse bearing an orthotopic brain tumour. As nanoparticles enter the blood stream, they diffuse through the disrupted blood–brain barrier and are sequestered and retained by the tumour. MPRs are too large to cross the intact blood–brain barrier and therefore cannot accumulate in healthy brain. Bottom: Proposed use of MPR technology in the clinical setting. Preoperative MRI allows for tumour localization and surgical planning. Only a single injection is necessary as the probe is retained allowing for intraoperative detection in the tumour several days post injection. Photoacoustic imaging with its relatively high resolution and deep tissue penetration is then able to guide bulk tumour resection intraoperatively. Raman imaging with its ultra-high sensitivity and spatial resolution can then be used to remove residual microscopic tumour burden. Resected specimen can subsequently be examined with a Raman probe ex vivo to verify clear margins (Reprinted from Ref. [25], with permission from Nature Publishing Group, Fig. 1). MPR: MRI-photoacoustic-Raman; MRI: magnetic resonance imaging.

Figure 3:

Schematic illustration of nanotechnology-based drug delivery platforms.

Figure 4:

Prevention of lung tumour growth in an in vivo model using paclitaxel-loaded expansile nanoparticles. (A) Paclitaxel-loaded expansile nanoparticles prevent tumour growth in vivo. Paclitaxel-loaded non-expansile nanoparticles, empty expansile nanoparticles and paclitaxel exhibit inferior antitumour efficacy. ^†P < 0.0005 vs control. (B) Tumour growth depicted over time for animals undergoing various treatments. Data displayed as mean (SEM. Day 11 *P < 0.05 vs control and Day 14 ^†P < 0.0005 vs control (reprinted from ref. [7], with permission from American Chemical Society, Fig. 5). SEM: standard error of the mean.

Figure 5:

Schematic illustration of multifunctional nanoparticles (reprinted from ref. [11], with permission from Annual Reviews, Inc., QD: quantum dot; GNP: gold nanoparticles; HfO; hafnium oxide nanoparticles; MNP: magnetic nanoparticles; UCNP: upconversion nanoparticles.

Figure 6:

Non-invasive, remote-controlled drug delivery in vitro using magnetic actuation of mechanized nanoparticles. (1 and 2) Zinc-doped iron oxide nanocrystals are synthetically positioned within a core of mesoporous silica nanoparticles. (3) A newly created molecular machine is attached to the surface of the nanoparticle. (4) Drug is loaded into the particle and capped. (5) Drug release is achieved using remote heating via the introduction of an oscillating magnetic field. The particles and machines are not drawn to scale (reprinted from ref. [67], with permission from American Chemical Society, Scheme 1).