Nanomicelle-Microsphere Composite as a Drug Carrier to Improve Lung-Targeting Specificity for Lung Cancer
Lung cancer is the second-most common cancer and has the highest mortality among all cancer types. Nanoparticle (NP) drug delivery systems have been used to improve the therapeutic effectiveness of lung cancer, but rapid clearance and poor targeting limit their clinical utility. Here, we developed a...
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MDPI AG
2022-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/3/510 |
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| author | Qianqian Zhang Jianwei Bao Tijie Duan Minxing Hu Yuting He Junwei Wang Rongfeng Hu Jihui Tang |
| author_facet | Qianqian Zhang Jianwei Bao Tijie Duan Minxing Hu Yuting He Junwei Wang Rongfeng Hu Jihui Tang |
| author_sort | Qianqian Zhang |
| collection | DOAJ |
| description | Lung cancer is the second-most common cancer and has the highest mortality among all cancer types. Nanoparticle (NP) drug delivery systems have been used to improve the therapeutic effectiveness of lung cancer, but rapid clearance and poor targeting limit their clinical utility. Here, we developed a nanomicelle-microsphere composite, in which doxorubicin (DOX) was loaded with spermine (Spm) modified poly (ethylene glycol)-poly(ε-caprolactone) (PEG-PCL) micelles, and then the nanomicelles were noncovalently adsorbed on the surface of poly (lactic-co-glycolic acid) (PLGA) microspheres. The attachment was confirmed by scanning electron microscopy and confocal microscopy. In vitro cell experiments, MTT assays and intracellular uptake assays were used to demonstrate the cytotoxicity and the cellular uptake of micelles in A549 cells. In vivo biodistribution studies were conducted, an orthotopic lung cancer implantation model based on C57BL/6 mice was established, and then real-time fluorescence imaging analysis was used to study the targeted efficacy of the complex. A nanomicelle-microsphere composite was successively constructed. Moreover, Spm-modified micelles significantly enhanced cytotoxicity and displayed more efficient cellular uptake. Notably, an orthotopic lung cancer implantation model based on C57BL/6 mice was also successively established, and in vivo biodistribution studies confirmed that the complex greatly improved the distribution of DOX in the lungs and displayed notable tumor targeting. These results suggested that the nanomicelle-microsphere composite has potential application prospects in the targeted treatment of lung cancer. |
| first_indexed | 2024-03-09T13:00:02Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T13:00:02Z |
| publishDate | 2022-02-01 |
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| series | Pharmaceutics |
| spelling | doaj.art-a17db15e75724c31922586360a1513632023-11-30T21:55:55ZengMDPI AGPharmaceutics1999-49232022-02-0114351010.3390/pharmaceutics14030510Nanomicelle-Microsphere Composite as a Drug Carrier to Improve Lung-Targeting Specificity for Lung CancerQianqian Zhang0Jianwei Bao1Tijie Duan2Minxing Hu3Yuting He4Junwei Wang5Rongfeng Hu6Jihui Tang7School of Pharmacy, Anhui Medical University, Hefei 230032, ChinaSchool of Pharmacy, Anhui Medical University, Hefei 230032, ChinaSchool of Pharmacy, Anhui Medical University, Hefei 230032, ChinaSchool of Pharmacy, Anhui Medical University, Hefei 230032, ChinaSchool of Pharmacy, Anhui Medical University, Hefei 230032, ChinaSchool of Pharmacy, Anhui Medical University, Hefei 230032, ChinaAnhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application, Key Laboratory of Xin’an Medicine, the Ministry of Education, Anhui Province Key Laboratory of Chinese Medicinal Formula, Plant Active Peptide Function Food Innovative Manufacturing Industry Innovation Team, Anhui University of Chinese Medicine, Hefei 230038, ChinaSchool of Pharmacy, Anhui Medical University, Hefei 230032, ChinaLung cancer is the second-most common cancer and has the highest mortality among all cancer types. Nanoparticle (NP) drug delivery systems have been used to improve the therapeutic effectiveness of lung cancer, but rapid clearance and poor targeting limit their clinical utility. Here, we developed a nanomicelle-microsphere composite, in which doxorubicin (DOX) was loaded with spermine (Spm) modified poly (ethylene glycol)-poly(ε-caprolactone) (PEG-PCL) micelles, and then the nanomicelles were noncovalently adsorbed on the surface of poly (lactic-co-glycolic acid) (PLGA) microspheres. The attachment was confirmed by scanning electron microscopy and confocal microscopy. In vitro cell experiments, MTT assays and intracellular uptake assays were used to demonstrate the cytotoxicity and the cellular uptake of micelles in A549 cells. In vivo biodistribution studies were conducted, an orthotopic lung cancer implantation model based on C57BL/6 mice was established, and then real-time fluorescence imaging analysis was used to study the targeted efficacy of the complex. A nanomicelle-microsphere composite was successively constructed. Moreover, Spm-modified micelles significantly enhanced cytotoxicity and displayed more efficient cellular uptake. Notably, an orthotopic lung cancer implantation model based on C57BL/6 mice was also successively established, and in vivo biodistribution studies confirmed that the complex greatly improved the distribution of DOX in the lungs and displayed notable tumor targeting. These results suggested that the nanomicelle-microsphere composite has potential application prospects in the targeted treatment of lung cancer.https://www.mdpi.com/1999-4923/14/3/510micellesmicrospherepolyamine transport systemtargeted drug delivery systemlung cancer |
| spellingShingle | Qianqian Zhang Jianwei Bao Tijie Duan Minxing Hu Yuting He Junwei Wang Rongfeng Hu Jihui Tang Nanomicelle-Microsphere Composite as a Drug Carrier to Improve Lung-Targeting Specificity for Lung Cancer Pharmaceutics micelles microsphere polyamine transport system targeted drug delivery system lung cancer |
| title | Nanomicelle-Microsphere Composite as a Drug Carrier to Improve Lung-Targeting Specificity for Lung Cancer |
| title_full | Nanomicelle-Microsphere Composite as a Drug Carrier to Improve Lung-Targeting Specificity for Lung Cancer |
| title_fullStr | Nanomicelle-Microsphere Composite as a Drug Carrier to Improve Lung-Targeting Specificity for Lung Cancer |
| title_full_unstemmed | Nanomicelle-Microsphere Composite as a Drug Carrier to Improve Lung-Targeting Specificity for Lung Cancer |
| title_short | Nanomicelle-Microsphere Composite as a Drug Carrier to Improve Lung-Targeting Specificity for Lung Cancer |
| title_sort | nanomicelle microsphere composite as a drug carrier to improve lung targeting specificity for lung cancer |
| topic | micelles microsphere polyamine transport system targeted drug delivery system lung cancer |
| url | https://www.mdpi.com/1999-4923/14/3/510 |
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