Development of PET Radioisotope Copper-64-Labeled Theranostic Immunoliposomes for EGFR Overexpressing Cancer-Targeted Therapy and Imaging
Combining standard surgical procedures with personalized chemotherapy and the continuous monitoring of cancer progression is necessary for effective NSCLC treatment. In this study, we developed liposomal nanoparticles as theranostic agents capable of simultaneous therapy for and imaging of target ca...
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MDPI AG
2024-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/3/1813 |
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| author | Hwa Yeon Jeong Seong Jae Kang Min Woo Kim In-ho Jeong Moon Jung Choi Cheulhee Jung In Ho Song Tae Sup Lee Yong Serk Park |
| author_facet | Hwa Yeon Jeong Seong Jae Kang Min Woo Kim In-ho Jeong Moon Jung Choi Cheulhee Jung In Ho Song Tae Sup Lee Yong Serk Park |
| author_sort | Hwa Yeon Jeong |
| collection | DOAJ |
| description | Combining standard surgical procedures with personalized chemotherapy and the continuous monitoring of cancer progression is necessary for effective NSCLC treatment. In this study, we developed liposomal nanoparticles as theranostic agents capable of simultaneous therapy for and imaging of target cancer cells. Copper-64 (<sup>64</sup>Cu), with a clinically practical half-life (<i>t</i><sub>1/2</sub> = 12.7 h) and decay properties, was selected as the radioisotope for molecular PET imaging. An anti-epidermal growth factor receptor (anti-EGFR) antibody was used to achieve target-specific delivery. Simultaneously, the chemotherapeutic agent doxorubicin (Dox) was encapsulated within the liposomes using a pH-gradient method. The conjugates of <sup>64</sup>Cu-labeled and anti-EGFR antibody-conjugated micelles were inserted into the doxorubicin-encapsulating liposomes via a post-insertion procedure (<sup>64</sup>Cu-Dox-immunoliposomes). We evaluated the size and zeta-potential of the liposomes and analyzed target-specific cell binding and cytotoxicity in EGFR-positive cell lines. Then, we analyzed the specific therapeutic effect and PET imaging of the <sup>64</sup>Cu-Dox-immunoliposomes with the A549 xenograft mouse model. In vivo therapeutic experiments on the mouse models demonstrated that the doxorubicin-containing <sup>64</sup>Cu-immunoliposomes effectively inhibited tumor growth. Moreover, the <sup>64</sup>Cu-immunoliposomes provided superior in vivo PET images of the tumors compared to the untargeted liposomes. We suggest that nanoparticles will be the potential platform for cancer treatment as a widely applicable theranostic system. |
| first_indexed | 2024-03-08T03:54:24Z |
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| id | doaj.art-2d219f25a7204d93b9af81abf548d4af |
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| language | English |
| last_indexed | 2024-03-08T03:54:24Z |
| publishDate | 2024-02-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2d219f25a7204d93b9af81abf548d4af2024-02-09T15:14:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01253181310.3390/ijms25031813Development of PET Radioisotope Copper-64-Labeled Theranostic Immunoliposomes for EGFR Overexpressing Cancer-Targeted Therapy and ImagingHwa Yeon Jeong0Seong Jae Kang1Min Woo Kim2In-ho Jeong3Moon Jung Choi4Cheulhee Jung5In Ho Song6Tae Sup Lee7Yong Serk Park8Department of Biomedical Laboratory Science, Yonsei University, Wonju 26493, Republic of KoreaDepartment of Biomedical Laboratory Science, Yonsei University, Wonju 26493, Republic of KoreaDepartment of Biomedical Laboratory Science, Yonsei University, Wonju 26493, Republic of KoreaDepartment of Biomedical Laboratory Science, Yonsei University, Wonju 26493, Republic of KoreaDepartment of Biomedical Laboratory Science, Yonsei University, Wonju 26493, Republic of KoreaDepartment of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of KoreaDivision of RI-Convergence Research, Korea Institute of Radiological and Medical Science, Seoul 01812, Republic of KoreaDivision of RI-Convergence Research, Korea Institute of Radiological and Medical Science, Seoul 01812, Republic of KoreaDepartment of Biomedical Laboratory Science, Yonsei University, Wonju 26493, Republic of KoreaCombining standard surgical procedures with personalized chemotherapy and the continuous monitoring of cancer progression is necessary for effective NSCLC treatment. In this study, we developed liposomal nanoparticles as theranostic agents capable of simultaneous therapy for and imaging of target cancer cells. Copper-64 (<sup>64</sup>Cu), with a clinically practical half-life (<i>t</i><sub>1/2</sub> = 12.7 h) and decay properties, was selected as the radioisotope for molecular PET imaging. An anti-epidermal growth factor receptor (anti-EGFR) antibody was used to achieve target-specific delivery. Simultaneously, the chemotherapeutic agent doxorubicin (Dox) was encapsulated within the liposomes using a pH-gradient method. The conjugates of <sup>64</sup>Cu-labeled and anti-EGFR antibody-conjugated micelles were inserted into the doxorubicin-encapsulating liposomes via a post-insertion procedure (<sup>64</sup>Cu-Dox-immunoliposomes). We evaluated the size and zeta-potential of the liposomes and analyzed target-specific cell binding and cytotoxicity in EGFR-positive cell lines. Then, we analyzed the specific therapeutic effect and PET imaging of the <sup>64</sup>Cu-Dox-immunoliposomes with the A549 xenograft mouse model. In vivo therapeutic experiments on the mouse models demonstrated that the doxorubicin-containing <sup>64</sup>Cu-immunoliposomes effectively inhibited tumor growth. Moreover, the <sup>64</sup>Cu-immunoliposomes provided superior in vivo PET images of the tumors compared to the untargeted liposomes. We suggest that nanoparticles will be the potential platform for cancer treatment as a widely applicable theranostic system.https://www.mdpi.com/1422-0067/25/3/1813theranosticspositron emission tomography (PET) imagingimmunoliposomesepidermal growth factor receptor (EGFR)copper-64 |
| spellingShingle | Hwa Yeon Jeong Seong Jae Kang Min Woo Kim In-ho Jeong Moon Jung Choi Cheulhee Jung In Ho Song Tae Sup Lee Yong Serk Park Development of PET Radioisotope Copper-64-Labeled Theranostic Immunoliposomes for EGFR Overexpressing Cancer-Targeted Therapy and Imaging International Journal of Molecular Sciences theranostics positron emission tomography (PET) imaging immunoliposomes epidermal growth factor receptor (EGFR) copper-64 |
| title | Development of PET Radioisotope Copper-64-Labeled Theranostic Immunoliposomes for EGFR Overexpressing Cancer-Targeted Therapy and Imaging |
| title_full | Development of PET Radioisotope Copper-64-Labeled Theranostic Immunoliposomes for EGFR Overexpressing Cancer-Targeted Therapy and Imaging |
| title_fullStr | Development of PET Radioisotope Copper-64-Labeled Theranostic Immunoliposomes for EGFR Overexpressing Cancer-Targeted Therapy and Imaging |
| title_full_unstemmed | Development of PET Radioisotope Copper-64-Labeled Theranostic Immunoliposomes for EGFR Overexpressing Cancer-Targeted Therapy and Imaging |
| title_short | Development of PET Radioisotope Copper-64-Labeled Theranostic Immunoliposomes for EGFR Overexpressing Cancer-Targeted Therapy and Imaging |
| title_sort | development of pet radioisotope copper 64 labeled theranostic immunoliposomes for egfr overexpressing cancer targeted therapy and imaging |
| topic | theranostics positron emission tomography (PET) imaging immunoliposomes epidermal growth factor receptor (EGFR) copper-64 |
| url | https://www.mdpi.com/1422-0067/25/3/1813 |
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