Multifunctional Lipid-Based Nanoparticles for Codelivery of Anticancer Drugs and siRNA for Treatment of Non-Small Cell Lung Cancer with Different Level of Resistance and EGFR Mutations
Resistance to chemotherapy, enhanced proliferation, invasion, angiogenesis, and metastasis (RPIAM) represent major obstacles that limit the efficacy of cancer treatment especially in advanced stages of cancer. Overcoming or suppressing RPIAM can dramatically improve the treatment outcome. Non-small...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/7/1063 |
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| author | Joydeb Majumder Tamara Minko |
| author_facet | Joydeb Majumder Tamara Minko |
| author_sort | Joydeb Majumder |
| collection | DOAJ |
| description | Resistance to chemotherapy, enhanced proliferation, invasion, angiogenesis, and metastasis (RPIAM) represent major obstacles that limit the efficacy of cancer treatment especially in advanced stages of cancer. Overcoming or suppressing RPIAM can dramatically improve the treatment outcome. Non-small cell lung cancer (NSCLC) is frequently diagnosed in an advanced stage and often possesses intrinsic resistance to chemotherapy accompanied by the fast development of acquired resistance during the treatment. Oncogenic receptor tyrosine kinases (TKs), specifically epidermal growth factor (EGF) TKs, play an important role in the activation of MAPK/PI3K/Akt/STAT pathways, finally leading to the development of RPIAM. However, the suppression of EGF-TK by different drugs is limited by various defensive mechanisms and mutations. In order to effectively prevent the development of RPIAM in NSCLC, we formulated and tested a multicomponent and multifunctional cancer targeted delivery system containing Nanostructured Lipid Carriers (NLCs) as vehicles, luteinizing hormone release hormone (LHRH) as a cancer targeting moiety, EFG-TK inhibitor gefitinib and/or paclitaxel as anticancer drug(s), siRNA targeted to EGF receptor (EGFR) mRNA as a suppressor of EGF receptors, and an imaging agent (rhodamine) for the visualization of cancer cells. Experimental data obtained show that this complex delivery system possesses significantly enhanced anticancer activity that cannot be achieved by individual components applied separately. |
| first_indexed | 2024-03-10T09:28:31Z |
| format | Article |
| id | doaj.art-b41f3542c03c4ad486da88f6aa453f58 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T09:28:31Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-b41f3542c03c4ad486da88f6aa453f582023-11-22T04:41:27ZengMDPI AGPharmaceutics1999-49232021-07-01137106310.3390/pharmaceutics13071063Multifunctional Lipid-Based Nanoparticles for Codelivery of Anticancer Drugs and siRNA for Treatment of Non-Small Cell Lung Cancer with Different Level of Resistance and EGFR MutationsJoydeb Majumder0Tamara Minko1Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USADepartment of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USAResistance to chemotherapy, enhanced proliferation, invasion, angiogenesis, and metastasis (RPIAM) represent major obstacles that limit the efficacy of cancer treatment especially in advanced stages of cancer. Overcoming or suppressing RPIAM can dramatically improve the treatment outcome. Non-small cell lung cancer (NSCLC) is frequently diagnosed in an advanced stage and often possesses intrinsic resistance to chemotherapy accompanied by the fast development of acquired resistance during the treatment. Oncogenic receptor tyrosine kinases (TKs), specifically epidermal growth factor (EGF) TKs, play an important role in the activation of MAPK/PI3K/Akt/STAT pathways, finally leading to the development of RPIAM. However, the suppression of EGF-TK by different drugs is limited by various defensive mechanisms and mutations. In order to effectively prevent the development of RPIAM in NSCLC, we formulated and tested a multicomponent and multifunctional cancer targeted delivery system containing Nanostructured Lipid Carriers (NLCs) as vehicles, luteinizing hormone release hormone (LHRH) as a cancer targeting moiety, EFG-TK inhibitor gefitinib and/or paclitaxel as anticancer drug(s), siRNA targeted to EGF receptor (EGFR) mRNA as a suppressor of EGF receptors, and an imaging agent (rhodamine) for the visualization of cancer cells. Experimental data obtained show that this complex delivery system possesses significantly enhanced anticancer activity that cannot be achieved by individual components applied separately.https://www.mdpi.com/1999-4923/13/7/1063EGFR mutated and gefitinib-resistant NSCLClipid nanoparticlessiRNALHRHpaclitaxel |
| spellingShingle | Joydeb Majumder Tamara Minko Multifunctional Lipid-Based Nanoparticles for Codelivery of Anticancer Drugs and siRNA for Treatment of Non-Small Cell Lung Cancer with Different Level of Resistance and EGFR Mutations Pharmaceutics EGFR mutated and gefitinib-resistant NSCLC lipid nanoparticles siRNA LHRH paclitaxel |
| title | Multifunctional Lipid-Based Nanoparticles for Codelivery of Anticancer Drugs and siRNA for Treatment of Non-Small Cell Lung Cancer with Different Level of Resistance and EGFR Mutations |
| title_full | Multifunctional Lipid-Based Nanoparticles for Codelivery of Anticancer Drugs and siRNA for Treatment of Non-Small Cell Lung Cancer with Different Level of Resistance and EGFR Mutations |
| title_fullStr | Multifunctional Lipid-Based Nanoparticles for Codelivery of Anticancer Drugs and siRNA for Treatment of Non-Small Cell Lung Cancer with Different Level of Resistance and EGFR Mutations |
| title_full_unstemmed | Multifunctional Lipid-Based Nanoparticles for Codelivery of Anticancer Drugs and siRNA for Treatment of Non-Small Cell Lung Cancer with Different Level of Resistance and EGFR Mutations |
| title_short | Multifunctional Lipid-Based Nanoparticles for Codelivery of Anticancer Drugs and siRNA for Treatment of Non-Small Cell Lung Cancer with Different Level of Resistance and EGFR Mutations |
| title_sort | multifunctional lipid based nanoparticles for codelivery of anticancer drugs and sirna for treatment of non small cell lung cancer with different level of resistance and egfr mutations |
| topic | EGFR mutated and gefitinib-resistant NSCLC lipid nanoparticles siRNA LHRH paclitaxel |
| url | https://www.mdpi.com/1999-4923/13/7/1063 |
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