| Autor: |
GUARNIERI, DANIELA, BIONDI, MARCO, BELLI, VALENTINA, FALANGA, ANDREA PATRIZIA, CANTISANI, MARCO, GALDIERO, STEFANIA, NETTI, PAOLO ANTONIO, Hui Yu |
| Přispěvatelé: |
Guarnieri, Daniela, Biondi, Marco, Hui, Yu, Belli, Valentina, Falanga, ANDREA PATRIZIA, Cantisani, Marco, Galdiero, Stefania, Netti, PAOLO ANTONIO |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Popis: |
A major issue in chemotherapy is the lack of specificity of many antitumor drugs, which cause severe side effects and an impaired therapeutic response. Here we report on the design and characterization of model tumor activated prodrug - conjugated polystyrene (PS) nanoparticles (TAP-NPs) for the release of doxorubicin (Dox) triggered by matrix metalloprotease-2 (MMP2) enzyme, which is overexpressed in the extracellular matrix of tumors. In particular, TAP NPs were produced by attaching Dox to poly(ethylene glycol) (PEG) through two MMP2-cleavable enzymes. The resulting adduct was then tethered to PS NPs. Results showed that Dox release was actually triggered by MMP2 cleavage and was dependent on enzyme concentration, with a plateau around 20 nM. Furthermore, significant cell cytotoxicity was observed towards three cell lines only in the presence of MMP2, but not in cells without enzyme pre-treatment, even after NP internalization by cells. These findings indicate the potential of TAP-NP as suitable nanocarriers for an on demand, tumor - specific delivery of antitumor drugs after the response to an endogenous stimulus. Further advancements will focus on the translation of this production technology to biodegradable systems for the safe transport of cytotoxic drug to tumor tissues. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
