Dual stimuli-responsive polyphosphazene-based molecular gates for controlled drug delivery in lung cancer cells.

Autor:	Salinas Y; Institute of Polymer Chemistry (ICP), Johannes Kepler University Linz (JKU) Altenberger Strasse 69 4040 Linz Austria yolanda.salinas@jku.at.; Linz Institute of Technology (LIT), Johannes Kepler University Linz (JKU) Altenberger Strasse 69 4040 Linz Austria., Kneidinger M; Institute of Polymer Chemistry (ICP), Johannes Kepler University Linz (JKU) Altenberger Strasse 69 4040 Linz Austria yolanda.salinas@jku.at., Fornaguera C; Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià (IQS), Universitat Ramon Llull (URL) Via Augusta 390 Barcelona 08017 Spain., Borrós S; Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià (IQS), Universitat Ramon Llull (URL) Via Augusta 390 Barcelona 08017 Spain., Brüggemann O; Institute of Polymer Chemistry (ICP), Johannes Kepler University Linz (JKU) Altenberger Strasse 69 4040 Linz Austria yolanda.salinas@jku.at., Teasdale I; Institute of Polymer Chemistry (ICP), Johannes Kepler University Linz (JKU) Altenberger Strasse 69 4040 Linz Austria yolanda.salinas@jku.at.; Linz Institute of Technology (LIT), Johannes Kepler University Linz (JKU) Altenberger Strasse 69 4040 Linz Austria.
Jazyk:	angličtina
Zdroj:	RSC advances [RSC Adv] 2020 Jul 21; Vol. 10 (46), pp. 27305-27314. Date of Electronic Publication: 2020 Jul 21 (Print Publication: 2020).
DOI:	10.1039/d0ra03210g
Abstrakt:	A switchable silane derived stimuli-responsive bottle-brush polyphosphazene (PPz) was prepared and attached to the surface of mesoporous silica nanoparticles (MSNs). The hybrid polymer with PEG-like Jeffamine® M-2005 side-arms undergo conformational changes in response to both pH and temperature due to its amphiphilic substituents and protonatable main-chain, hence were investigated as a gatekeeper. Safranin O as control fluorophore or the anticancer drug camptothecin (CPT) were encapsulated in the PPz-coated MSNs. At temperatures below the lower critical solution temperature (LCST), the swollen conformation of PPz efficiently blocked the cargo within the pores. However, above the LCST, the PPz collapsed, allowing release of the payload. Additionally, protonation of the polymer backbone at lower pH values was observed to enhance opening of the pores from the surface of the MSNs and therefore the release of the dye. In vitro studies demonstrated the ability of these nanoparticles loaded with the drug camptothecin to be endocytosed in both models of tumor (A549) and healthy epithelial (BEAS-2B) lung cells. Their accumulation and the release of the chemotherapeutic drug, co-localized within lysosomes, was faster and higher for tumor than for healthy cells, further, the biocompatibility of PPz-gated nanosystem without drug was demonstrated. Tailored dual responsive polyphosphazenes thus represent novel and promising candidates in the construction of future gated mesoporous silica nanocarriers designs for lung cancer-directed treatment. Competing Interests: There are no conflicts to declare. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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