A peptide probe enables photoacoustic-guided imaging and drug delivery to lung tumors in K-Rasla2 mutant mice

Hyunkyung Jung, Sungjo Park, Gowri Rangaswamy Gunassekaran, Mansik Jeon, Young Eun Cho, Moon Chang Baek, Jae Yong Park, Gayong Shim, Yu Kyoung Oh, In-San Kim, Chulhong Kim, Byungheon Lee

Research output: Contribution to journalArticle

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-rasLA2 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-rasLA2 mutant mice. Analysis of hematologic parameters and liver and kidney function showed no significant systemic side effects by the treatments. Affinity-based 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 photoacoustic-guided detection and drug delivery to lung cancer, and acts by binding to TNFRSF19L.

Original languageEnglish
Pages (from-to)4271-4282
Number of pages12
JournalCancer Research
Volume79
Issue number16
DOIs
Publication statusPublished - 2019 Aug 15

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Lung
Peptides
Pharmaceutical Preparations
Neoplasms
Doxorubicin
Lung Neoplasms
Tumor Necrosis Factor Receptors
Liposomes
Bacteriophages
Peptide Receptors
Liver
Coloring Agents
Fluorescence
Tomography
Kidney
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Jung, H., Park, S., Gunassekaran, G. R., Jeon, M., Cho, Y. E., Baek, M. C., ... Lee, B. (2019). A peptide probe enables photoacoustic-guided imaging and drug delivery to lung tumors in K-Rasla2 mutant mice. Cancer Research, 79(16), 4271-4282. https://doi.org/10.1158/0008-5472.CAN-18-3089

A peptide probe enables photoacoustic-guided imaging and drug delivery to lung tumors in K-Rasla2 mutant mice. / Jung, Hyunkyung; Park, Sungjo; Gunassekaran, Gowri Rangaswamy; Jeon, Mansik; Cho, Young Eun; Baek, Moon Chang; Park, Jae Yong; Shim, Gayong; Oh, Yu Kyoung; Kim, In-San; Kim, Chulhong; Lee, Byungheon.

In: Cancer Research, Vol. 79, No. 16, 15.08.2019, p. 4271-4282.

Research output: Contribution to journalArticle

Jung, H, Park, S, Gunassekaran, GR, Jeon, M, Cho, YE, Baek, MC, Park, JY, Shim, G, Oh, YK, Kim, I-S, Kim, C & Lee, B 2019, 'A peptide probe enables photoacoustic-guided imaging and drug delivery to lung tumors in K-Rasla2 mutant mice', Cancer Research, vol. 79, no. 16, pp. 4271-4282. https://doi.org/10.1158/0008-5472.CAN-18-3089
Jung, Hyunkyung ; Park, Sungjo ; Gunassekaran, Gowri Rangaswamy ; Jeon, Mansik ; Cho, Young Eun ; Baek, Moon Chang ; Park, Jae Yong ; Shim, Gayong ; Oh, Yu Kyoung ; Kim, In-San ; Kim, Chulhong ; Lee, Byungheon. / A peptide probe enables photoacoustic-guided imaging and drug delivery to lung tumors in K-Rasla2 mutant mice. In: Cancer Research. 2019 ; Vol. 79, No. 16. pp. 4271-4282.
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