Alveolar Macrophages-Mediated Translocation of Intratracheally Delivered Perfluorocarbon Nanoparticles to Achieve Lung Cancer ¹⁹F-MR Imaging

Abstract

Recent advances in intratracheal delivery strategies have sparked considerable biomedical interest in developing this promising approach for lung cancer diagnosis and treatment. However, there are very few relevant studies on the behavior and mechanism of imaging nanoparticles (NPs) after intratracheal delivery. Here, we found that nanosized perfluoro-15-crown-5-ether (PFCE NPs, ∼200 nm) exhibite significant 19F-MRI signal-to-noise ratio (SNR) enhancement than perfluorooctyl bromide (PFOB NPs) up to day 7 after intratracheal delivery. Alveolar macrophages (AMs) engulf PFCE NPs, become PFCE NPs-laden AMs, and then migrate into the tumor margin, resulting in increased tumor PFCE concentration and 19F-MRI signals. AMs-mediated translocation of PFCE NPs to lung draning lymph nodes (dLNs) decreases the background PFCE concentration. Our results shed light on the dynamic AMs-mediated translocation of intratracheally delivered PFC NPs for effective lung tumor visualization and reveal a pathway to develop and promote the clinical translation of an intratracheal delivery-based imaging strategy.

Nanostructured Microparticles Repolarize Macrophages and Induce Cell Death in an In Vitro Model of Tumour-Associated Macrophages

“…The dominant clearance mechanism in the deep lungs is internalization by professional phagocytes, e.g., alveolar macrophages (AMs) [ 44 ], which are, in contrast to lung epithelial or endothelial cells, the only cells which take up particles bigger than ~0.5 µm [ 45 ]. It has been shown in mice that AMs take up particles and infiltrate lung tumour margins [ 17 ]. In addition to stromal TAM density, alveolar TAM density has been described to be significantly associated with a variety of biological and clinical factors (e.g., tumour differentiation, pathological stage) as well as with a poor prognosis in NSCLC patients [ 46 ].…”

“…With lung cancer macrophages being addressable with inhalable particulate systems [ 17 ], the aim of this work was to employ poly(I:C)-loaded µRs as drug delivery system to specifically target and repolarize TAMs by exploiting their phagocytic ability. We showed limited suitability of the frequently used THP-1 cell line to model TAMs and therefore undertook the biological characterization of µR actions in primary human TAM-like MΦs.…”

Macrophage based drug delivery: Key challenges and strategies

“…Similarly, because synovial tissue macrophages (STMs) predominate immune cells in synovial tissue and play a role in maintaining and reinstating synovial homeostasis, STM subpopulations (MerTK pos TREM2 high and MerTK pos LYVE1 pos ) have been shown to have the anti-inflammatory function and repair response of synovial fibroblasts with the potential to produce anti-inflammatory lipid mediators for the treatment of rheumatoid arthritis [ 62 ]. Wang and colleagues employed AMs as a carrier to deliver perfluorine-15-crown-5-ether nanoparticles (PFCE NPs) to the alveolar space and pulmonary interstitium to further infiltrate into lung tumors [ 63 ]. Subsequently, Nguyen et al isolated and differentiated macrophages from the spleens of BALB/c mice as cell vehicles that could avoid an immune response when injected into a host animal [ 45 ].…”

Pulmonary delivery of nano‐particles for lung cancer diagnosis and therapy: Recent advances and future prospects

“…PFCE NPs crossed through epithelial barriers and mucus, were captured by alveolar macrophages (AMs), and further migrated into the tumor margins, increasing the tumor PFCE concentration and 19 F-MRI signals. Moreover, PFCE NP-laden AMs could also translocate to lung draining lymph nodes (DLNs) and decrease the background PFCE concentration (Wang et al, 2023).…”

“…Even when the tumor is located far from the airways, pulmonary‐delivered NPs can reach the tumor site through the bronchial and pulmonary circulation, enabling lung cancer imaging and therapy (Wang et al, 2020). Our previous study described that liposome‐encapsulated perfluoro‐15‐crown‐5‐ether (PFCE) NPs of ∼200 nm could be easily visualized by 19 F‐MR imaging after pulmonary delivery (Wang et al, 2023). PFCE NPs crossed through epithelial barriers and mucus, were captured by alveolar macrophages (AMs), and further migrated into the tumor margins, increasing the tumor PFCE concentration and 19 F‐MRI signals.…”