Lung Cancer Targeted Chemoradiotherapy via Dual-Stimuli Responsive Biodegradable Core-Shell Nanoparticles
Lung cancer is one of the major causes of cancer-related deaths worldwide, primarily because of the limitations of conventional clinical therapies such as chemotherapy and radiation therapy. Side effects associated with these treatments have made it essential for new modalities, such as tumor target...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/8/1525 |
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| author | Roshni Iyer Harish Ramachandramoorthy Trinh Nguyen Cancan Xu Huikang Fu Tanviben Kotadia Benjamin Chen Yi Hong Debabrata Saha Kytai Truong Nguyen |
| author_facet | Roshni Iyer Harish Ramachandramoorthy Trinh Nguyen Cancan Xu Huikang Fu Tanviben Kotadia Benjamin Chen Yi Hong Debabrata Saha Kytai Truong Nguyen |
| author_sort | Roshni Iyer |
| collection | DOAJ |
| description | Lung cancer is one of the major causes of cancer-related deaths worldwide, primarily because of the limitations of conventional clinical therapies such as chemotherapy and radiation therapy. Side effects associated with these treatments have made it essential for new modalities, such as tumor targeting nanoparticles that can provide cancer specific therapies. In this research, we have developed novel dual-stimuli nanoparticles (E-DSNPs), comprised of two parts; (1) Core: responsive to glutathione as stimuli and encapsulating Cisplatin (a chemo-drug), and (2) Shell: responsive to irradiation as stimuli and containing NU7441 (a radiation sensitizer). The targeting moieties on these nanoparticles are Ephrin transmembrane receptors A2 (EphA2) that are highly expressed on the surfaces of lung cancer cells. These nanoparticles were then evaluated for their enhanced targeting and therapeutic efficiency against lung cancer cell lines. E-DSNPs displayed very high uptake by lung cancer cells compared to healthy lung epithelial cells. These nanoparticles also demonstrated a triggered release of both drugs against respective stimuli and a subsequent reduction in in vitro cancer cell survival fraction compared to free drugs of equivalent concentration (survival fraction of about 0.019 and 0.19, respectively). Thus, these nanoparticles could potentially pave the path to targeted cancer therapy, while overcoming the side effects of conventional clinical therapies. |
| first_indexed | 2024-03-09T12:47:18Z |
| format | Article |
| id | doaj.art-c9c36c4a2cc04b1f82ba0f2fbc3d4cde |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T12:47:18Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-c9c36c4a2cc04b1f82ba0f2fbc3d4cde2023-11-30T22:10:44ZengMDPI AGPharmaceutics1999-49232022-07-01148152510.3390/pharmaceutics14081525Lung Cancer Targeted Chemoradiotherapy via Dual-Stimuli Responsive Biodegradable Core-Shell NanoparticlesRoshni Iyer0Harish Ramachandramoorthy1Trinh Nguyen2Cancan Xu3Huikang Fu4Tanviben Kotadia5Benjamin Chen6Yi Hong7Debabrata Saha8Kytai Truong Nguyen9Department of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USADepartment of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USADepartment of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USADepartment of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USADepartment of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USADepartment of Biology, University of Texas at Arlington, Arlington, TX 76019, USADepartment of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USADepartment of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USADepartment of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USADepartment of Bioengineering, University of Texas at Arlington, Arlington, TX 76019, USALung cancer is one of the major causes of cancer-related deaths worldwide, primarily because of the limitations of conventional clinical therapies such as chemotherapy and radiation therapy. Side effects associated with these treatments have made it essential for new modalities, such as tumor targeting nanoparticles that can provide cancer specific therapies. In this research, we have developed novel dual-stimuli nanoparticles (E-DSNPs), comprised of two parts; (1) Core: responsive to glutathione as stimuli and encapsulating Cisplatin (a chemo-drug), and (2) Shell: responsive to irradiation as stimuli and containing NU7441 (a radiation sensitizer). The targeting moieties on these nanoparticles are Ephrin transmembrane receptors A2 (EphA2) that are highly expressed on the surfaces of lung cancer cells. These nanoparticles were then evaluated for their enhanced targeting and therapeutic efficiency against lung cancer cell lines. E-DSNPs displayed very high uptake by lung cancer cells compared to healthy lung epithelial cells. These nanoparticles also demonstrated a triggered release of both drugs against respective stimuli and a subsequent reduction in in vitro cancer cell survival fraction compared to free drugs of equivalent concentration (survival fraction of about 0.019 and 0.19, respectively). Thus, these nanoparticles could potentially pave the path to targeted cancer therapy, while overcoming the side effects of conventional clinical therapies.https://www.mdpi.com/1999-4923/14/8/1525nanoparticlesstimuli-responsivetargeted drug deliverychemoradiotherapy |
| spellingShingle | Roshni Iyer Harish Ramachandramoorthy Trinh Nguyen Cancan Xu Huikang Fu Tanviben Kotadia Benjamin Chen Yi Hong Debabrata Saha Kytai Truong Nguyen Lung Cancer Targeted Chemoradiotherapy via Dual-Stimuli Responsive Biodegradable Core-Shell Nanoparticles Pharmaceutics nanoparticles stimuli-responsive targeted drug delivery chemoradiotherapy |
| title | Lung Cancer Targeted Chemoradiotherapy via Dual-Stimuli Responsive Biodegradable Core-Shell Nanoparticles |
| title_full | Lung Cancer Targeted Chemoradiotherapy via Dual-Stimuli Responsive Biodegradable Core-Shell Nanoparticles |
| title_fullStr | Lung Cancer Targeted Chemoradiotherapy via Dual-Stimuli Responsive Biodegradable Core-Shell Nanoparticles |
| title_full_unstemmed | Lung Cancer Targeted Chemoradiotherapy via Dual-Stimuli Responsive Biodegradable Core-Shell Nanoparticles |
| title_short | Lung Cancer Targeted Chemoradiotherapy via Dual-Stimuli Responsive Biodegradable Core-Shell Nanoparticles |
| title_sort | lung cancer targeted chemoradiotherapy via dual stimuli responsive biodegradable core shell nanoparticles |
| topic | nanoparticles stimuli-responsive targeted drug delivery chemoradiotherapy |
| url | https://www.mdpi.com/1999-4923/14/8/1525 |
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