Thermosensitive Cationic Magnetic Liposomes for Thermoresponsive Delivery of CPT-11 and SLP2 shRNA in Glioblastoma Treatment
Thermosensitive cationic magnetic liposomes (TCMLs), prepared from dipalmitoylphosphatidylcholine (DPPC), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)]-2000, and didodecyldimethylammonium bromide (DDAB) were used in this study for the controlled releas...
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MDPI AG
2023-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/4/1169 |
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| author | Yu-Jen Lu Hao-Lung Hsu Yu-Hsiang Lan Jyh-Ping Chen |
| author_facet | Yu-Jen Lu Hao-Lung Hsu Yu-Hsiang Lan Jyh-Ping Chen |
| author_sort | Yu-Jen Lu |
| collection | DOAJ |
| description | Thermosensitive cationic magnetic liposomes (TCMLs), prepared from dipalmitoylphosphatidylcholine (DPPC), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)]-2000, and didodecyldimethylammonium bromide (DDAB) were used in this study for the controlled release of drug/gene for cancer treatment. After co-entrapping citric-acid-coated magnetic nanoparticles (MNPs) and the chemotherapeutic drug irinotecan (CPT-11) in the core of TCML (TCML@CPT-11), SLP2 shRNA plasmids were complexed with DDAB in the lipid bilayer to prepare TCML@CPT-11/shRNA with a 135.6 ± 2.1 nm diameter. As DPPC has a melting temperature slightly above the physiological temperature, drug release from the liposomes can be triggered by an increase in solution temperature or by magneto-heating induced with an alternating magnetic field (AMF). The MNPs in the liposomes also endow the TCMLs with magnetically targeted drug delivery with guidance by a magnetic field. The successful preparation of drug-loaded liposomes was confirmed by various physical and chemical methods. Enhanced drug release, from 18% to 59%, at pH 7.4 was observed when raising the temperature from 37 to 43 °C, as well as during induction with an AMF. The in vitro cell culture experiments endorse the biocompatibility of TCMLs, whereas TCML@CPT-11 shows some enhancement of cytotoxicity toward U87 human glioblastoma cells when compared with free CPT-11. The U87 cells can be transfected with the SLP2 shRNA plasmids with very high efficiency (~100%), leading to silencing of the SLP2 gene and reducing the migration ability of U87 from 63% to 24% in a wound-healing assay. Finally, an in vivo study, using subcutaneously implanted U87 xenografts in nude mice, demonstrates that the intravenous injection of TCML@CPT11-shRNA, plus magnetic guidance and AMF treatment, can provide a safe and promising therapeutic modality for glioblastoma treatment. |
| first_indexed | 2024-03-11T04:37:52Z |
| format | Article |
| id | doaj.art-01ee24eb894b4f3480b1616863ea14d7 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T04:37:52Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-01ee24eb894b4f3480b1616863ea14d72023-11-17T20:53:42ZengMDPI AGPharmaceutics1999-49232023-04-01154116910.3390/pharmaceutics15041169Thermosensitive Cationic Magnetic Liposomes for Thermoresponsive Delivery of CPT-11 and SLP2 shRNA in Glioblastoma TreatmentYu-Jen Lu0Hao-Lung Hsu1Yu-Hsiang Lan2Jyh-Ping Chen3Department of Chemical and Materials and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, TaiwanDepartment of Chemical and Materials and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, TaiwanDepartment of Neurosurgery, Chang Gung Memorial Hospital at Linkou, School of Medicine, Chang Gung University, Kwei-San, Taoyuan 33305, TaiwanDepartment of Chemical and Materials and Materials Engineering, Chang Gung University, Kwei-San, Taoyuan 33302, TaiwanThermosensitive cationic magnetic liposomes (TCMLs), prepared from dipalmitoylphosphatidylcholine (DPPC), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)]-2000, and didodecyldimethylammonium bromide (DDAB) were used in this study for the controlled release of drug/gene for cancer treatment. After co-entrapping citric-acid-coated magnetic nanoparticles (MNPs) and the chemotherapeutic drug irinotecan (CPT-11) in the core of TCML (TCML@CPT-11), SLP2 shRNA plasmids were complexed with DDAB in the lipid bilayer to prepare TCML@CPT-11/shRNA with a 135.6 ± 2.1 nm diameter. As DPPC has a melting temperature slightly above the physiological temperature, drug release from the liposomes can be triggered by an increase in solution temperature or by magneto-heating induced with an alternating magnetic field (AMF). The MNPs in the liposomes also endow the TCMLs with magnetically targeted drug delivery with guidance by a magnetic field. The successful preparation of drug-loaded liposomes was confirmed by various physical and chemical methods. Enhanced drug release, from 18% to 59%, at pH 7.4 was observed when raising the temperature from 37 to 43 °C, as well as during induction with an AMF. The in vitro cell culture experiments endorse the biocompatibility of TCMLs, whereas TCML@CPT-11 shows some enhancement of cytotoxicity toward U87 human glioblastoma cells when compared with free CPT-11. The U87 cells can be transfected with the SLP2 shRNA plasmids with very high efficiency (~100%), leading to silencing of the SLP2 gene and reducing the migration ability of U87 from 63% to 24% in a wound-healing assay. Finally, an in vivo study, using subcutaneously implanted U87 xenografts in nude mice, demonstrates that the intravenous injection of TCML@CPT11-shRNA, plus magnetic guidance and AMF treatment, can provide a safe and promising therapeutic modality for glioblastoma treatment.https://www.mdpi.com/1999-4923/15/4/1169liposomeschemotherapydrug deliverymagnetic nanoparticlescancer therapy |
| spellingShingle | Yu-Jen Lu Hao-Lung Hsu Yu-Hsiang Lan Jyh-Ping Chen Thermosensitive Cationic Magnetic Liposomes for Thermoresponsive Delivery of CPT-11 and SLP2 shRNA in Glioblastoma Treatment Pharmaceutics liposomes chemotherapy drug delivery magnetic nanoparticles cancer therapy |
| title | Thermosensitive Cationic Magnetic Liposomes for Thermoresponsive Delivery of CPT-11 and SLP2 shRNA in Glioblastoma Treatment |
| title_full | Thermosensitive Cationic Magnetic Liposomes for Thermoresponsive Delivery of CPT-11 and SLP2 shRNA in Glioblastoma Treatment |
| title_fullStr | Thermosensitive Cationic Magnetic Liposomes for Thermoresponsive Delivery of CPT-11 and SLP2 shRNA in Glioblastoma Treatment |
| title_full_unstemmed | Thermosensitive Cationic Magnetic Liposomes for Thermoresponsive Delivery of CPT-11 and SLP2 shRNA in Glioblastoma Treatment |
| title_short | Thermosensitive Cationic Magnetic Liposomes for Thermoresponsive Delivery of CPT-11 and SLP2 shRNA in Glioblastoma Treatment |
| title_sort | thermosensitive cationic magnetic liposomes for thermoresponsive delivery of cpt 11 and slp2 shrna in glioblastoma treatment |
| topic | liposomes chemotherapy drug delivery magnetic nanoparticles cancer therapy |
| url | https://www.mdpi.com/1999-4923/15/4/1169 |
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