Dual stimuli-responsive polyphosphazene-based molecular gates for controlled drug delivery in lung cancer cells
Author
Fornaguera Puigvert, Cristina
Borrós i Gómez, Salvador
Salinas, Yolanda
Kneidinger, Michael
Bruggemann, Oliver
Teasdale, Ian
Other authors
Universitat Ramon Llull. IQS
Publication date
2020-07Abstract
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.
Document Type
Article
Published version
Language
English
Subject (CDU)
54 - Chemistry. Crystallography. Mineralogy
Keywords
Termoreceptors
Nanopartícules
Nanomedicina
Polímers
Salt-induced thermoresponsivity
Hybrid materials
Nanoparticles
Nanomedicine
Hydrogels
Polymers
Pages
10 p.
Publisher
Royal Society of Chemistry
Is part of
RSC Advances. Vol.10, n.46 (2020), p.27305-27314
Grant agreement number
info:eu-repo/grantAgreement/SUR del DEC/SGR/2017-SGR-1551
info:eu-repo/grantAgreement/MINECO-AEI-FEDER/PN I+D/RTI2018-094734-B-C22
This item appears in the following Collection(s)
Rights
© The Royal Society of Chemistry
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/