Co-delivery of VEGF siRNA and Etoposide for Enhanced Anti-angiogenesis and Anti-proliferation Effect via Multi-functional Nanoparticles for Orthotopic Non-Small Cell Lung Cancer Treatment
Targeting tumor angiogenesis pathway VEGF siRNA (siVEGF) has shown great potential in treating highly malignant and metastatic non-small cell lung cancer (NSCLC). However, anti-angiogenic monotherapy lacked sufficient antitumor efficacy which suffered from malignant tumor proliferation. Therefore, t...
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Published in | Theranostics Vol. 9; no. 20; pp. 5886 - 5898 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
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Abstract | Targeting tumor angiogenesis pathway
VEGF siRNA (siVEGF) has shown great potential in treating highly malignant and metastatic non-small cell lung cancer (NSCLC). However, anti-angiogenic monotherapy lacked sufficient antitumor efficacy which suffered from malignant tumor proliferation. Therefore, the combined application of siVEGF and chemotherapeutic agents for simultaneous targeting of tumor proliferation and angiogenesis has been a research hotspot to explore a promising NSCLC therapy regimen.
We designed, for the first time, a rational therapy strategy
intelligently co-delivering siVEGF and chemotherapeutics etoposide (ETO) by multi-functional nanoparticles (NPs) directed against the orthotopic NSCLC. These NPs consisted of cationic liposomes loaded with siVEGF and ETO and then coated with versatile polymer PEGylated histidine-grafted chitosan-lipoic acid (PHCL). We then comprehensively evaluated the anti-angiogenic and anti-proliferation efficiency in the
tumor cell model and in bioluminescent orthotopic lung tumor bearing mice model.
The NPs co-delivering siVEGF and ETO exhibited tailor-made surface charge reversal features in mimicking tumor extracellular environment with improved internal tumor penetration capacity and higher cellular internalization. Furthermore, these NPs with flexible particles size triggered by intracellular acidic environment and redox environment showed pinpointed and sharp intracellular cargo release guaranteeing adequate active drug concentration in tumor cells. Enhanced VEGF gene expression silencing efficacy and improved tumor cell anti-proliferation effect were demonstrated
. In addition, the PHCL layer improved the stability of these NPs in neutral environment allowing enhanced orthotopic lung tumor targeting efficiency
. The combined therapy by siVEGF and ETO co-delivered NPs for orthotopic NSCLC simultaneously inhibited tumor proliferation and tumor angiogenesis resulting in more significant suppression of tumor growth and metastasis than monotherapy.
Combined application of siVEGF and ETO by the multi-functional NPs with excellent and on-demand properties exhibited the desired antitumor effect on the orthotopic lung tumor. Our work has significant potential in promoting combined anti-angiogenesis therapy and chemotherapy regimen for clinical NSCLC treatment. |
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AbstractList | Targeting tumor angiogenesis pathway via VEGF siRNA (siVEGF) has shown great potential in treating highly malignant and metastatic non-small cell lung cancer (NSCLC). However, anti-angiogenic monotherapy lacked sufficient antitumor efficacy which suffered from malignant tumor proliferation. Therefore, the combined application of siVEGF and chemotherapeutic agents for simultaneous targeting of tumor proliferation and angiogenesis has been a research hotspot to explore a promising NSCLC therapy regimen. Methods: We designed, for the first time, a rational therapy strategy via intelligently co-delivering siVEGF and chemotherapeutics etoposide (ETO) by multi-functional nanoparticles (NPs) directed against the orthotopic NSCLC. These NPs consisted of cationic liposomes loaded with siVEGF and ETO and then coated with versatile polymer PEGylated histidine-grafted chitosan-lipoic acid (PHCL). We then comprehensively evaluated the anti-angiogenic and anti-proliferation efficiency in the in vitro tumor cell model and in bioluminescent orthotopic lung tumor bearing mice model. Results: The NPs co-delivering siVEGF and ETO exhibited tailor-made surface charge reversal features in mimicking tumor extracellular environment with improved internal tumor penetration capacity and higher cellular internalization. Furthermore, these NPs with flexible particles size triggered by intracellular acidic environment and redox environment showed pinpointed and sharp intracellular cargo release guaranteeing adequate active drug concentration in tumor cells. Enhanced VEGF gene expression silencing efficacy and improved tumor cell anti-proliferation effect were demonstrated in vitro. In addition, the PHCL layer improved the stability of these NPs in neutral environment allowing enhanced orthotopic lung tumor targeting efficiency in vivo. The combined therapy by siVEGF and ETO co-delivered NPs for orthotopic NSCLC simultaneously inhibited tumor proliferation and tumor angiogenesis resulting in more significant suppression of tumor growth and metastasis than monotherapy. Conclusion: Combined application of siVEGF and ETO by the multi-functional NPs with excellent and on-demand properties exhibited the desired antitumor effect on the orthotopic lung tumor. Our work has significant potential in promoting combined anti-angiogenesis therapy and chemotherapy regimen for clinical NSCLC treatment. Targeting tumor angiogenesis pathway via VEGF siRNA (siVEGF) has shown great potential in treating highly malignant and metastatic non-small cell lung cancer (NSCLC). However, anti-angiogenic monotherapy lacked sufficient antitumor efficacy which suffered from malignant tumor proliferation. Therefore, the combined application of siVEGF and chemotherapeutic agents for simultaneous targeting of tumor proliferation and angiogenesis has been a research hotspot to explore a promising NSCLC therapy regimen. Methods: We designed, for the first time, a rational therapy strategy via intelligently co-delivering siVEGF and chemotherapeutics etoposide (ETO) by multi-functional nanoparticles (NPs) directed against the orthotopic NSCLC. These NPs consisted of cationic liposomes loaded with siVEGF and ETO and then coated with versatile polymer PEGylated histidine-grafted chitosan-lipoic acid (PHCL). We then comprehensively evaluated the anti-angiogenic and anti-proliferation efficiency in the in vitro tumor cell model and in bioluminescent orthotopic lung tumor bearing mice model. Results: The NPs co-delivering siVEGF and ETO exhibited tailor-made surface charge reversal features in mimicking tumor extracellular environment with improved internal tumor penetration capacity and higher cellular internalization. Furthermore, these NPs with flexible particles size triggered by intracellular acidic environment and redox environment showed pinpointed and sharp intracellular cargo release guaranteeing adequate active drug concentration in tumor cells. Enhanced VEGF gene expression silencing efficacy and improved tumor cell anti-proliferation effect were demonstrated in vitro . In addition, the PHCL layer improved the stability of these NPs in neutral environment allowing enhanced orthotopic lung tumor targeting efficiency in vivo . The combined therapy by siVEGF and ETO co-delivered NPs for orthotopic NSCLC simultaneously inhibited tumor proliferation and tumor angiogenesis resulting in more significant suppression of tumor growth and metastasis than monotherapy. Conclusion: Combined application of siVEGF and ETO by the multi-functional NPs with excellent and on-demand properties exhibited the desired antitumor effect on the orthotopic lung tumor. Our work has significant potential in promoting combined anti-angiogenesis therapy and chemotherapy regimen for clinical NSCLC treatment. Targeting tumor angiogenesis pathway VEGF siRNA (siVEGF) has shown great potential in treating highly malignant and metastatic non-small cell lung cancer (NSCLC). However, anti-angiogenic monotherapy lacked sufficient antitumor efficacy which suffered from malignant tumor proliferation. Therefore, the combined application of siVEGF and chemotherapeutic agents for simultaneous targeting of tumor proliferation and angiogenesis has been a research hotspot to explore a promising NSCLC therapy regimen. We designed, for the first time, a rational therapy strategy intelligently co-delivering siVEGF and chemotherapeutics etoposide (ETO) by multi-functional nanoparticles (NPs) directed against the orthotopic NSCLC. These NPs consisted of cationic liposomes loaded with siVEGF and ETO and then coated with versatile polymer PEGylated histidine-grafted chitosan-lipoic acid (PHCL). We then comprehensively evaluated the anti-angiogenic and anti-proliferation efficiency in the tumor cell model and in bioluminescent orthotopic lung tumor bearing mice model. The NPs co-delivering siVEGF and ETO exhibited tailor-made surface charge reversal features in mimicking tumor extracellular environment with improved internal tumor penetration capacity and higher cellular internalization. Furthermore, these NPs with flexible particles size triggered by intracellular acidic environment and redox environment showed pinpointed and sharp intracellular cargo release guaranteeing adequate active drug concentration in tumor cells. Enhanced VEGF gene expression silencing efficacy and improved tumor cell anti-proliferation effect were demonstrated . In addition, the PHCL layer improved the stability of these NPs in neutral environment allowing enhanced orthotopic lung tumor targeting efficiency . The combined therapy by siVEGF and ETO co-delivered NPs for orthotopic NSCLC simultaneously inhibited tumor proliferation and tumor angiogenesis resulting in more significant suppression of tumor growth and metastasis than monotherapy. Combined application of siVEGF and ETO by the multi-functional NPs with excellent and on-demand properties exhibited the desired antitumor effect on the orthotopic lung tumor. Our work has significant potential in promoting combined anti-angiogenesis therapy and chemotherapy regimen for clinical NSCLC treatment. |
Author | Chen, Wei-Liang You, Ben-Gang Li, Fang Wang, Yu Chen, Meng-Tian Qu, Chen-Xi Yang, Shu-di Liu, Yang Wang, Dan-Dan Zhang, Xue-Nong Zhou, Ye-Juan |
AuthorAffiliation | 1 Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China 2 Department of Pharmacy, Children` s Hospital of Soochow University, Suzhou 215025, People's Republic of China |
AuthorAffiliation_xml | – name: 2 Department of Pharmacy, Children` s Hospital of Soochow University, Suzhou 215025, People's Republic of China – name: 1 Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China |
Author_xml | – sequence: 1 givenname: Fang surname: Li fullname: Li, Fang organization: Department of Pharmacy, Children` s Hospital of Soochow University, Suzhou 215025, People's Republic of China – sequence: 2 givenname: Yu surname: Wang fullname: Wang, Yu organization: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China – sequence: 3 givenname: Wei-Liang surname: Chen fullname: Chen, Wei-Liang organization: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China – sequence: 4 givenname: Dan-Dan surname: Wang fullname: Wang, Dan-Dan organization: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China – sequence: 5 givenname: Ye-Juan surname: Zhou fullname: Zhou, Ye-Juan organization: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China – sequence: 6 givenname: Ben-Gang surname: You fullname: You, Ben-Gang organization: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China – sequence: 7 givenname: Yang surname: Liu fullname: Liu, Yang organization: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China – sequence: 8 givenname: Chen-Xi surname: Qu fullname: Qu, Chen-Xi organization: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China – sequence: 9 givenname: Shu-di surname: Yang fullname: Yang, Shu-di organization: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China – sequence: 10 givenname: Meng-Tian surname: Chen fullname: Chen, Meng-Tian organization: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China – sequence: 11 givenname: Xue-Nong surname: Zhang fullname: Zhang, Xue-Nong organization: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People's Republic of China |
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Keywords | co-delivery combined therapy etoposide multi-functional nanoparticles VEGF siRNA anti-angiogenesis |
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Snippet | Targeting tumor angiogenesis pathway
VEGF siRNA (siVEGF) has shown great potential in treating highly malignant and metastatic non-small cell lung cancer... Targeting tumor angiogenesis pathway via VEGF siRNA (siVEGF) has shown great potential in treating highly malignant and metastatic non-small cell lung cancer... Targeting tumor angiogenesis pathway via VEGF siRNA (siVEGF) has shown great potential in treating highly malignant and metastatic non-small cell lung cancer... |
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StartPage | 5886 |
SubjectTerms | Adsorption Angiogenesis Apoptosis Blood vessels Cancer therapies Chemotherapy Lung cancer Metastasis Microscopy Nanoparticles Phase transitions Polymers Research Paper Vascular endothelial growth factor |
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Title | Co-delivery of VEGF siRNA and Etoposide for Enhanced Anti-angiogenesis and Anti-proliferation Effect via Multi-functional Nanoparticles for Orthotopic Non-Small Cell Lung Cancer Treatment |
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