A Peptide Probe Enables Photoacoustic-Guided Imaging and Drug Delivery to Lung Tumors in K-rasLA2 Mutant Mice

Abstract

The lack of molecular targets and targeting probes remains a major drawback for targeted imaging and drug delivery in lung cancer. In this study, we exploited in vivo phage display to identify a novel targeting probe that homes to the tumor in a K-ras LA2 mutant mouse lung cancer model. Compared with other candidate peptides selected from 5 rounds of phage display, the CRQTKN peptide homed to tumor nodules in the lung of mutant mice at higher levels. Photoacoustic tomography of mutant mice detected lung tumors via tumor homing of the near-infrared fluorescence dye-labeled CRQTKN peptide. Ex vivo photoacoustic images of isolated organs further demonstrated tumor homing of the CRQTKN peptide, whereas minimal accumulation was observed in control organs, such as the liver. Compared with untargeted liposomes and doxorubicin, doxorubicin-loaded liposomes whose surface was modified with the CRQTKN peptide more efficiently delivered doxorubicin and reduced the number or size of tumor lesions in K-ras LA2 mutant mice. Analysis of hematologic parameters and liver and kidney function showed no significant systemic side effects by the treatments. Affinitybased identification was used to detect TNF receptor superfamily member 19L (TNFRSF19L), which was upregulated in lung tumors of mutant mice, as the receptor for the CRQTKN peptide. In conclusion, these results suggest that the CRQTKN peptide is a promising targeting probe for photoacousticguided detection and drug delivery to lung cancer, and acts by binding to TNFRSF19L. Significance: These findings present a new tumor-targeting probe for photoacoustic-guided detection and drug delivery.

Nanomedicine in lung cancer: Current states of overcoming drug resistance and improving cancer immunotherapy

“…In vitro, aspartate‐modified liposomes showed increased intracellular delivery and in the presence of glycine, the cellular uptake was notably decreased in the competitive endocytosis study (Luo et al, 2017). There are many similar examples, including tumor‐homing peptide, tLyp‐1 to target neuropilin‐1 (Jin, Zhou, Zhang, & Lv, 2018), peptides HSP1, HSP2, and HSP4 to target both NSCLC and SCLC (Figure 1) (Chi et al, 2017), RGD peptide to target integrin ligand (Chen et al, 2018; Jiang, Shen, & Xu, 2018; Zou et al, 2018), CRQTKN peptide to target TNF receptor superfamily member 19 L (Jung et al, 2019), transferrin to target transferrin receptors (TfR) (Chen & Liu, 2018; Muralidharan et al, 2017), folic acid (FA) to target folate receptor (FR) (Chen & Liu, 2018) and cetuximab (CTX) to target EGFR(Lu et al, 2019).…”

A photoacoustic finder fully integrated with a solid-state dye laser and transparent ultrasound transducer

“…Advantageously, PA imaging can delineate SLNs in deep tissue with high resolution and high contrast. However, PA SLN imaging based on blue (methylene blue, MB) or green (indocyanine green, ICG) dyes requires expensive and bulky laser systems such as Q-switched Nd:Yag pumped optical parametric oscillators, Ti: Sapphire lasers, or liquid dye lasers [ [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] ]. Thus, these systems are not yet widespread in clinical settings.…”

Towards clinical photoacoustic and ultrasound imaging: Probe improvement and real-time graphical user interface

“…2–4 The PA imaging also provides functional information 5–8 as well as molecular information of biological tissue by using exogenous contrast agents. 9–17 Thanks to the combination of optical and US imaging techniques, PA imaging overcomes the associated drawbacks of each modality achieving much deeper imaging depth compared to pure optical imaging and enhanced optical contrast compared to US imaging.…”