Development of an Acid-Labile Ketal Linked Amphiphilic Block Copolymer Nanoparticles for pH-Triggered Release of Paclitaxel
Here, we report on the construction of biodegradable poly(ethylene oxide monomethyl ether) (MPEO)-<i>b</i>-poly(ε-caprolactone) (PCL) nanoparticles (NPs) having acid-labile (acyclic ketal group) linkage at the block junction. In the presence of acidic pH, the nanoassemblies were destabil...
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MDPI AG
2021-05-01
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| Series: | Polymers |
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| Online Access: | https://www.mdpi.com/2073-4360/13/9/1465 |
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| author | Svetlana Lukáš Petrova Eliézer Jäger Alessandro Jäger Anita Höcherl Rafał Konefał Alexander Zhigunov Ewa Pavlova Olga Janoušková Martin Hrubý |
| author_facet | Svetlana Lukáš Petrova Eliézer Jäger Alessandro Jäger Anita Höcherl Rafał Konefał Alexander Zhigunov Ewa Pavlova Olga Janoušková Martin Hrubý |
| author_sort | Svetlana Lukáš Petrova |
| collection | DOAJ |
| description | Here, we report on the construction of biodegradable poly(ethylene oxide monomethyl ether) (MPEO)-<i>b</i>-poly(ε-caprolactone) (PCL) nanoparticles (NPs) having acid-labile (acyclic ketal group) linkage at the block junction. In the presence of acidic pH, the nanoassemblies were destabilized as a consequence of cleaving this linkage. The amphiphilic MPEO-<i>b</i>-PCL diblock copolymer self-assembled in PBS solution into regular spherical NPs. The structure of self-assemble and disassemble NPs were characterized in detail by dynamic (DLS), static (SLS) light scattering, small-angle X-ray scattering (SAXS), and transmission electron microscopy (TEM). The key of the obtained NPs is using them in a paclitaxel (PTX) delivery system and study their in vitro cytostatic activity in a cancer cell model. The acid-labile ketal linker enabled the disassembly of the NPs in a buffer simulating an acidic environment in endosomal (pH ~5.0 to ~6.0) and lysosomal (pH ~4.0 to ~5.0) cell compartments resulting in the release of paclitaxel (PTX) and formation of neutral degradation products. The in vitro cytotoxicity studies showed that the activity of the drug-loaded NPs was increased compared to the free PTX. The ability of the NPs to release the drug at the endosomal pH with concomitant high cytotoxicity makes them suitable candidates as a drug delivery system for cancer therapy. |
| first_indexed | 2024-03-10T11:46:03Z |
| format | Article |
| id | doaj.art-3c3a5d1f5fbb4f7393a326fd97d28eda |
| institution | Directory Open Access Journal |
| issn | 2073-4360 |
| language | English |
| last_indexed | 2024-03-10T11:46:03Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Polymers |
| spelling | doaj.art-3c3a5d1f5fbb4f7393a326fd97d28eda2023-11-21T18:05:47ZengMDPI AGPolymers2073-43602021-05-01139146510.3390/polym13091465Development of an Acid-Labile Ketal Linked Amphiphilic Block Copolymer Nanoparticles for pH-Triggered Release of PaclitaxelSvetlana Lukáš Petrova0Eliézer Jäger1Alessandro Jäger2Anita Höcherl3Rafał Konefał4Alexander Zhigunov5Ewa Pavlova6Olga Janoušková7Martin Hrubý8Institute of Macromolecular Chemistry v.v.i., Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague, Czech RepublicInstitute of Macromolecular Chemistry v.v.i., Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague, Czech RepublicInstitute of Macromolecular Chemistry v.v.i., Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague, Czech RepublicInstitute of Macromolecular Chemistry v.v.i., Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague, Czech RepublicInstitute of Macromolecular Chemistry v.v.i., Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague, Czech RepublicInstitute of Macromolecular Chemistry v.v.i., Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague, Czech RepublicInstitute of Macromolecular Chemistry v.v.i., Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague, Czech RepublicInstitute of Macromolecular Chemistry v.v.i., Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague, Czech RepublicInstitute of Macromolecular Chemistry v.v.i., Academy of Sciences of the Czech Republic, Heyrovsky Sq. 2, 162 06 Prague, Czech RepublicHere, we report on the construction of biodegradable poly(ethylene oxide monomethyl ether) (MPEO)-<i>b</i>-poly(ε-caprolactone) (PCL) nanoparticles (NPs) having acid-labile (acyclic ketal group) linkage at the block junction. In the presence of acidic pH, the nanoassemblies were destabilized as a consequence of cleaving this linkage. The amphiphilic MPEO-<i>b</i>-PCL diblock copolymer self-assembled in PBS solution into regular spherical NPs. The structure of self-assemble and disassemble NPs were characterized in detail by dynamic (DLS), static (SLS) light scattering, small-angle X-ray scattering (SAXS), and transmission electron microscopy (TEM). The key of the obtained NPs is using them in a paclitaxel (PTX) delivery system and study their in vitro cytostatic activity in a cancer cell model. The acid-labile ketal linker enabled the disassembly of the NPs in a buffer simulating an acidic environment in endosomal (pH ~5.0 to ~6.0) and lysosomal (pH ~4.0 to ~5.0) cell compartments resulting in the release of paclitaxel (PTX) and formation of neutral degradation products. The in vitro cytotoxicity studies showed that the activity of the drug-loaded NPs was increased compared to the free PTX. The ability of the NPs to release the drug at the endosomal pH with concomitant high cytotoxicity makes them suitable candidates as a drug delivery system for cancer therapy.https://www.mdpi.com/2073-4360/13/9/1465MPEO-<i>b</i>-PCL nanoparticlesacyclic ketal grouppaclitaxelhuman HeLa carcinoma cells |
| spellingShingle | Svetlana Lukáš Petrova Eliézer Jäger Alessandro Jäger Anita Höcherl Rafał Konefał Alexander Zhigunov Ewa Pavlova Olga Janoušková Martin Hrubý Development of an Acid-Labile Ketal Linked Amphiphilic Block Copolymer Nanoparticles for pH-Triggered Release of Paclitaxel Polymers MPEO-<i>b</i>-PCL nanoparticles acyclic ketal group paclitaxel human HeLa carcinoma cells |
| title | Development of an Acid-Labile Ketal Linked Amphiphilic Block Copolymer Nanoparticles for pH-Triggered Release of Paclitaxel |
| title_full | Development of an Acid-Labile Ketal Linked Amphiphilic Block Copolymer Nanoparticles for pH-Triggered Release of Paclitaxel |
| title_fullStr | Development of an Acid-Labile Ketal Linked Amphiphilic Block Copolymer Nanoparticles for pH-Triggered Release of Paclitaxel |
| title_full_unstemmed | Development of an Acid-Labile Ketal Linked Amphiphilic Block Copolymer Nanoparticles for pH-Triggered Release of Paclitaxel |
| title_short | Development of an Acid-Labile Ketal Linked Amphiphilic Block Copolymer Nanoparticles for pH-Triggered Release of Paclitaxel |
| title_sort | development of an acid labile ketal linked amphiphilic block copolymer nanoparticles for ph triggered release of paclitaxel |
| topic | MPEO-<i>b</i>-PCL nanoparticles acyclic ketal group paclitaxel human HeLa carcinoma cells |
| url | https://www.mdpi.com/2073-4360/13/9/1465 |
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