Modified gefitinib conjugated Fe3O4 NPs for improved delivery of chemo drugs following an image-guided mechanistic study of inner vs. outer tumor uptake for the treatment of non-small cell lung cancer
Gefitinib (GEF) is an FDA-approved anti-cancer drug for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC). However, the efficacy of anticancer drugs is limited due to their non-specificity, lower accumulation at target sites, and systemic toxicity. Herein, we su...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1272492/full |
| _version_ | 1827796785432625152 |
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| author | Suresh Thangudu Suresh Thangudu Ching-Yi Tsai Wei-Che Lin Chia-Hao Su Chia-Hao Su Chia-Hao Su |
| author_facet | Suresh Thangudu Suresh Thangudu Ching-Yi Tsai Wei-Che Lin Chia-Hao Su Chia-Hao Su Chia-Hao Su |
| author_sort | Suresh Thangudu |
| collection | DOAJ |
| description | Gefitinib (GEF) is an FDA-approved anti-cancer drug for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC). However, the efficacy of anticancer drugs is limited due to their non-specificity, lower accumulation at target sites, and systemic toxicity. Herein, we successfully synthesized a modified GEF (mGEF) drug and conjugated to Iron oxide nanoparticles (Fe3O4 NPs) for the treatment of NSCLC via magnetic resonance (MR) image-guided drug delivery. A traditional EDC coupling pathway uses mGEF to directly conjugate to Fe3O4 NPs to overcom the drug leakage issues. As a result, we found in vitro drug delivery on mGEF- Fe3O4 NPs exhibits excellent anticancer effects towards the PC9 cells selectively, with an estimated IC 50 value of 2.0 μM. Additionally, in vivo MRI and PET results demonstrate that the NPs could accumulate in tumor-specific regions with localized cell growth inhibition. Results also revealed that outer tumor region exhibiting a stronger contrast than the tinner tumor region which may due necrosis in inner tumor region. In vivo biodistribution further confirms Fe3O4 NPs are more biocompatible and are excreated after the treatment. Overall, we believe that this current strategy of drug modification combined with chemical conjugation on magnetic NPs will lead to improved cancer chemotherapy as well as understanding the tumor microenvironments for better therapeutic outcomes. |
| first_indexed | 2024-03-11T19:11:59Z |
| format | Article |
| id | doaj.art-4db77553c6cc442887317028d88de760 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-03-11T19:11:59Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-4db77553c6cc442887317028d88de7602023-10-09T11:18:55ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852023-10-011110.3389/fbioe.2023.12724921272492Modified gefitinib conjugated Fe3O4 NPs for improved delivery of chemo drugs following an image-guided mechanistic study of inner vs. outer tumor uptake for the treatment of non-small cell lung cancerSuresh Thangudu0Suresh Thangudu1Ching-Yi Tsai2Wei-Che Lin3Chia-Hao Su4Chia-Hao Su5Chia-Hao Su6Center for General Education, Chang Gung University, Taoyuan, TaiwanCanary Center for Cancer Early Detection, Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, United StatesInstitute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, TaiwanDepartment of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, TaiwanCenter for General Education, Chang Gung University, Taoyuan, TaiwanDepartment of Biomedical Imaging and Radiological Sciences, National Yang-Ming Chiao Tung University, Taipei, TaiwanDepartment of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, TaiwanGefitinib (GEF) is an FDA-approved anti-cancer drug for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC). However, the efficacy of anticancer drugs is limited due to their non-specificity, lower accumulation at target sites, and systemic toxicity. Herein, we successfully synthesized a modified GEF (mGEF) drug and conjugated to Iron oxide nanoparticles (Fe3O4 NPs) for the treatment of NSCLC via magnetic resonance (MR) image-guided drug delivery. A traditional EDC coupling pathway uses mGEF to directly conjugate to Fe3O4 NPs to overcom the drug leakage issues. As a result, we found in vitro drug delivery on mGEF- Fe3O4 NPs exhibits excellent anticancer effects towards the PC9 cells selectively, with an estimated IC 50 value of 2.0 μM. Additionally, in vivo MRI and PET results demonstrate that the NPs could accumulate in tumor-specific regions with localized cell growth inhibition. Results also revealed that outer tumor region exhibiting a stronger contrast than the tinner tumor region which may due necrosis in inner tumor region. In vivo biodistribution further confirms Fe3O4 NPs are more biocompatible and are excreated after the treatment. Overall, we believe that this current strategy of drug modification combined with chemical conjugation on magnetic NPs will lead to improved cancer chemotherapy as well as understanding the tumor microenvironments for better therapeutic outcomes.https://www.frontiersin.org/articles/10.3389/fbioe.2023.1272492/fulliron oxide NPsmodified gefitinibnon-small cell lung cancerdrug deliverymagnetic resonance imaging |
| spellingShingle | Suresh Thangudu Suresh Thangudu Ching-Yi Tsai Wei-Che Lin Chia-Hao Su Chia-Hao Su Chia-Hao Su Modified gefitinib conjugated Fe3O4 NPs for improved delivery of chemo drugs following an image-guided mechanistic study of inner vs. outer tumor uptake for the treatment of non-small cell lung cancer Frontiers in Bioengineering and Biotechnology iron oxide NPs modified gefitinib non-small cell lung cancer drug delivery magnetic resonance imaging |
| title | Modified gefitinib conjugated Fe3O4 NPs for improved delivery of chemo drugs following an image-guided mechanistic study of inner vs. outer tumor uptake for the treatment of non-small cell lung cancer |
| title_full | Modified gefitinib conjugated Fe3O4 NPs for improved delivery of chemo drugs following an image-guided mechanistic study of inner vs. outer tumor uptake for the treatment of non-small cell lung cancer |
| title_fullStr | Modified gefitinib conjugated Fe3O4 NPs for improved delivery of chemo drugs following an image-guided mechanistic study of inner vs. outer tumor uptake for the treatment of non-small cell lung cancer |
| title_full_unstemmed | Modified gefitinib conjugated Fe3O4 NPs for improved delivery of chemo drugs following an image-guided mechanistic study of inner vs. outer tumor uptake for the treatment of non-small cell lung cancer |
| title_short | Modified gefitinib conjugated Fe3O4 NPs for improved delivery of chemo drugs following an image-guided mechanistic study of inner vs. outer tumor uptake for the treatment of non-small cell lung cancer |
| title_sort | modified gefitinib conjugated fe3o4 nps for improved delivery of chemo drugs following an image guided mechanistic study of inner vs outer tumor uptake for the treatment of non small cell lung cancer |
| topic | iron oxide NPs modified gefitinib non-small cell lung cancer drug delivery magnetic resonance imaging |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1272492/full |
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