Nanocarriers based on block copolymers of l-proline and lactide: The effect of core crosslinking versus its pH-sensitivity on their cellular uptake
| Autor: | Marek Brzeziński, Marta Socka, Weronika Gonciarz, Bartłomiej Kost, Agnieszka Krupa, M. Rogala |
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| Rok vydání: | 2021 |
| Předmět: |
Lactide
Polymers and Plastics Chemistry Organic Chemistry technology industry and agriculture General Physics and Astronomy Nanoparticle Chain transfer macromolecular substances 02 engineering and technology Raft 010402 general chemistry 021001 nanoscience & nanotechnology 01 natural sciences 0104 chemical sciences chemistry.chemical_compound Polymerization Materials Chemistry Copolymer Biophysics Nanocarriers 0210 nano-technology Cytotoxicity |
| Zdroj: | European Polymer Journal. 156:110572 |
| ISSN: | 0014-3057 |
| DOI: | 10.1016/j.eurpolymj.2021.110572 |
| Popis: | Although doxorubicin (DOX) is an effective drug with cytotoxicity against a variety of different tumors, it also induces undesired side-effects to the healthy tissues. Therefore, the smart nanocarrier-based systems are the solution for this problem due to the entrapment of the drug in the stimuli-responsive, polymeric core which, as a result, decreases the toxicity of the DOX and allows for the delivery of DOX precisely to the tumor sites. Herein, we present such a smart nanoparticle platform composed of stimuli-responsive copolymers of l , l -lactide/ d , d -lactide with l -proline, which were successfully synthesized through the combination of ring-opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. These copolymers were used for the preparation of enantiomeric and stereocomplexed nanoparticles (NPs) with a mean diameter of about 160-210 nm that were used as a reservoir of the anticancer drug. The drug release results showed that (co)polymeric NPs possess an excellent pH-sensitive behavior under the acidic tumor microenvironment, however, it was less pronounced for NPs cross-linked by stereocomplexation between poly( l -lactide) (PLLA) and poly( d -lactide) PDLA chains. Additionally, the DOX-loaded NPs were effective against AGS, HeLa, and Lovo cells, nevertheless, their cytotoxicity strongly depends on the building blocks of the nanocarrier. Interestingly, the l -proline functionality enhances the cellular uptake of enantiomeric NPs, nonetheless, the high stability of NPs due to the supramolecular crosslinking of PLA macromolecules prevails over this effect and stereocomplexed NPs were better internalized by the cancer cells. These advantageous features indicate that stereocomplexed (sc), (co)polymeric NPs are promising candidates as a smart and versatile nanocarrier platform for the treatment of different types of tumors. |
| Databáze: | OpenAIRE |
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