Preparation and In Vitro and In Vivo Antitumor Effects of VEGF Targeting Micelles
Background: Doxorubicin (DOX) has antitumor effects mediated by cell viability inhibition and by inducing cellular apoptosis. However, it has limited use in clinical applications due to various factors such as hydrophobicity, dose-dependent toxicity effects on normal tissues, short cycle retention t...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2020-09-01
|
| Series: | Technology in Cancer Research & Treatment |
| Online Access: | https://doi.org/10.1177/1533033820957022 |
| _version_ | 1828334907914452992 |
|---|---|
| author | Jing Chang MD Zhe Yang BD Junfeng Li MD Yufen Jin MD Yihang Gao MD Yanwen Sun MD Hainan Li MD Ting Yu PhD |
| author_facet | Jing Chang MD Zhe Yang BD Junfeng Li MD Yufen Jin MD Yihang Gao MD Yanwen Sun MD Hainan Li MD Ting Yu PhD |
| author_sort | Jing Chang MD |
| collection | DOAJ |
| description | Background: Doxorubicin (DOX) has antitumor effects mediated by cell viability inhibition and by inducing cellular apoptosis. However, it has limited use in clinical applications due to various factors such as hydrophobicity, dose-dependent toxicity effects on normal tissues, short cycle retention time, and low targeting ability. This study aims at enhancing hydrophilicity of DOX to restrict its toxic effects to within or around the tumor sites and also to improve its targeting ability to enhance antitumor efficiency. Methods: Micelles composed of biodegradable poly (ethylene glycol)-poly (lactic acid) copolymers (PEG-PLA) were employed to deliver DOX via a self-assembly method and were coupled to VEGF antibodies. The morphology, size, and physical stability of PEG-PLA-DOX targeting VEGF micelles (VEGF-PEG-PLA-DOX micelles) were assessed. Then, the release ability of DOX from these micelles was monitored, and their drug loading capacity was calculated. MTT assay revealed the in vitro antitumor effect of VEGF-PEG-PLA-DOX micelles. Moreover, ROS release was measured to evaluate apoptotic effects of these nanoparticle micelles. In vivo therapeutic efficiencies of VEGF-PEG-PLA-DOX micelles on a lung cancer nude mouse model was evaluated. Results: DOX-loaded micelles were obtained with a drug loading capacity of 12.2% and were monodisperse with 220 nm average diameter and a controlled in vitro DOX release for extended periods. In addition, VEGF-PEG-PLA-DOX micelles displayed a larger cell viability inhibitory effect as measured via MTT assays and greater cell apoptosis induction through in vitro ROS levels compared with PEG-PLA-DOX micelles or free DOX. Furthermore, VEGF-PEG-PLA-DOX micelles could improve in vivo antitumor effects of DOX by reducing tumor volume and weight. Conclusions: VEGF-PEG-PLA-DOX micelles displayed a larger anti-tumor effect both in in vitro A549 cells and in an in vivo lung cancer nude mouse model compared with PEG-PLA-DOX micelles or free DOX, and hence they have potential clinical applications in human lung cancer therapy. |
| first_indexed | 2024-04-13T21:38:27Z |
| format | Article |
| id | doaj.art-df828e2e905d4c52a789317b9afc7def |
| institution | Directory Open Access Journal |
| issn | 1533-0338 |
| language | English |
| last_indexed | 2024-04-13T21:38:27Z |
| publishDate | 2020-09-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Technology in Cancer Research & Treatment |
| spelling | doaj.art-df828e2e905d4c52a789317b9afc7def2022-12-22T02:28:51ZengSAGE PublishingTechnology in Cancer Research & Treatment1533-03382020-09-011910.1177/1533033820957022Preparation and In Vitro and In Vivo Antitumor Effects of VEGF Targeting MicellesJing Chang MD0Zhe Yang BD1Junfeng Li MD2Yufen Jin MD3Yihang Gao MD4Yanwen Sun MD5Hainan Li MD6Ting Yu PhD7 , Nanguan District, Changchun, China , Nanguan District, Changchun, China , Nanguan District, Changchun, China , Nanguan District, Changchun, China , Nanguan District, Changchun, China The First Affiliated Hospital of Zhejiang Chinese Medical University, Shangcheng District, Hangzhou, China , Nanguan District, Changchun, China , Nanguan District, Changchun, ChinaBackground: Doxorubicin (DOX) has antitumor effects mediated by cell viability inhibition and by inducing cellular apoptosis. However, it has limited use in clinical applications due to various factors such as hydrophobicity, dose-dependent toxicity effects on normal tissues, short cycle retention time, and low targeting ability. This study aims at enhancing hydrophilicity of DOX to restrict its toxic effects to within or around the tumor sites and also to improve its targeting ability to enhance antitumor efficiency. Methods: Micelles composed of biodegradable poly (ethylene glycol)-poly (lactic acid) copolymers (PEG-PLA) were employed to deliver DOX via a self-assembly method and were coupled to VEGF antibodies. The morphology, size, and physical stability of PEG-PLA-DOX targeting VEGF micelles (VEGF-PEG-PLA-DOX micelles) were assessed. Then, the release ability of DOX from these micelles was monitored, and their drug loading capacity was calculated. MTT assay revealed the in vitro antitumor effect of VEGF-PEG-PLA-DOX micelles. Moreover, ROS release was measured to evaluate apoptotic effects of these nanoparticle micelles. In vivo therapeutic efficiencies of VEGF-PEG-PLA-DOX micelles on a lung cancer nude mouse model was evaluated. Results: DOX-loaded micelles were obtained with a drug loading capacity of 12.2% and were monodisperse with 220 nm average diameter and a controlled in vitro DOX release for extended periods. In addition, VEGF-PEG-PLA-DOX micelles displayed a larger cell viability inhibitory effect as measured via MTT assays and greater cell apoptosis induction through in vitro ROS levels compared with PEG-PLA-DOX micelles or free DOX. Furthermore, VEGF-PEG-PLA-DOX micelles could improve in vivo antitumor effects of DOX by reducing tumor volume and weight. Conclusions: VEGF-PEG-PLA-DOX micelles displayed a larger anti-tumor effect both in in vitro A549 cells and in an in vivo lung cancer nude mouse model compared with PEG-PLA-DOX micelles or free DOX, and hence they have potential clinical applications in human lung cancer therapy.https://doi.org/10.1177/1533033820957022 |
| spellingShingle | Jing Chang MD Zhe Yang BD Junfeng Li MD Yufen Jin MD Yihang Gao MD Yanwen Sun MD Hainan Li MD Ting Yu PhD Preparation and In Vitro and In Vivo Antitumor Effects of VEGF Targeting Micelles Technology in Cancer Research & Treatment |
| title | Preparation and In Vitro and In Vivo Antitumor Effects of VEGF Targeting Micelles |
| title_full | Preparation and In Vitro and In Vivo Antitumor Effects of VEGF Targeting Micelles |
| title_fullStr | Preparation and In Vitro and In Vivo Antitumor Effects of VEGF Targeting Micelles |
| title_full_unstemmed | Preparation and In Vitro and In Vivo Antitumor Effects of VEGF Targeting Micelles |
| title_short | Preparation and In Vitro and In Vivo Antitumor Effects of VEGF Targeting Micelles |
| title_sort | preparation and in vitro and in vivo antitumor effects of vegf targeting micelles |
| url | https://doi.org/10.1177/1533033820957022 |
| work_keys_str_mv | AT jingchangmd preparationandinvitroandinvivoantitumoreffectsofvegftargetingmicelles AT zheyangbd preparationandinvitroandinvivoantitumoreffectsofvegftargetingmicelles AT junfenglimd preparationandinvitroandinvivoantitumoreffectsofvegftargetingmicelles AT yufenjinmd preparationandinvitroandinvivoantitumoreffectsofvegftargetingmicelles AT yihanggaomd preparationandinvitroandinvivoantitumoreffectsofvegftargetingmicelles AT yanwensunmd preparationandinvitroandinvivoantitumoreffectsofvegftargetingmicelles AT hainanlimd preparationandinvitroandinvivoantitumoreffectsofvegftargetingmicelles AT tingyuphd preparationandinvitroandinvivoantitumoreffectsofvegftargetingmicelles |