Nanotherapeutics shielded with a pH responsive polymeric layer

0448519 - ÚMCH 2016 RIV CZ eng J - Journal Article
Kostka, Libor - Šubr, Vladimír - Laga, Richard - Chytil, Petr - Ulbrich, Karel - Seymour, L. W. - Etrych, Tomáš
Nanotherapeutics shielded with a pH responsive polymeric layer.
Physiological Research. Roč. 64, Suppl. 1 (2015), S29-S40. ISSN 0862-8408. E-ISSN 1802-9973
R&D Projects: GA MŠMT(CZ) EE2.3.30.0029; GA MŠMT(CZ) ED1.1.00/02.0109; GA ČR(CZ) GAP301/12/1254
Institutional support: RVO:61389013
Keywords : nanotherapeutics * coating * pH responsive
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 1.643, year: 2015
http://www.biomed.cas.cz/physiolres/pdf/64%20Suppl%201/64_S29.pdf

Efficient intravenous delivery is the greatest single hurdle, with most nanotherapeutics frequently found to be unstable in the harsh conditions of the bloodstream. In the case of nanotherapeutics for gene delivery, viral vectors are often avidly recognized by both the innate and the adaptive immune systems. So, most modern delivery systems have benefited from being coated with hydrophilic polymers. Self-assembling delivery systems can achieve both steric and lateral stabilization following surface coating, endowing them with much improved systemic circulation properties and better access to disseminated targets; similarly, gene delivery viral vectors can be ‘stealthed’ and their physical properties modulated by surface coating. Polymers that start degrading under acidic conditions are increasingly investigated as a pathway to trigger the release of drugs or genes once the carrier reaches a slightly acidic tumor environment or after the carrier has been taken up by cells, resulting in the localization of the polymer in acidic endosomes and lysosomes. Advances in the design of acid-degradable drug and gene delivery systems have been focused and discussed in this article with stress placed on HPMA-based copolymers. We designed a system that is able to “throw away” the polymer coat after successful transport of the vector into a target cell. Initial biological studies were performed and it was demonstrated that this principle is applicable for real adenoviral vectors. It was shown that the transfection ability of coated virus at pH 7.4 is 75 times lower then transfection at pH 5.4.
Permanent Link: http://hdl.handle.net/11104/0252995