Poly-Gamma-Glutamic Acid (γ-PGA)-Based Encapsulation of Adenovirus to Evade Neutralizing Antibodies
Ibrahim R. Khalil,
Martin P. Khechara,
Sathishkumar Kurusamy,
Angel L. Armesilla,
Abhishek Gupta,
Barbara Mendrek,
Tamara Khalaf,
Mariastella Scandola,
Maria Letizia Focarete,
Marek Kowalczuk,
Iza Radecka
Affiliations
Ibrahim R. Khalil
Wolverhampton School of Sciences, Faculty of Science and Engineering, University of Wolverhampton, Wulfruna Street, Wolverhampton WV1 1LY, UK
Martin P. Khechara
Wolverhampton School of Sciences, Faculty of Science and Engineering, University of Wolverhampton, Wulfruna Street, Wolverhampton WV1 1LY, UK
Sathishkumar Kurusamy
Wolverhampton School of Sciences, Faculty of Science and Engineering, University of Wolverhampton, Wulfruna Street, Wolverhampton WV1 1LY, UK
Angel L. Armesilla
Wolverhampton School of Sciences, Faculty of Science and Engineering, University of Wolverhampton, Wulfruna Street, Wolverhampton WV1 1LY, UK
Abhishek Gupta
Wolverhampton School of Sciences, Faculty of Science and Engineering, University of Wolverhampton, Wulfruna Street, Wolverhampton WV1 1LY, UK
Barbara Mendrek
Centre of Polymer and Carbon Materials, Polish Academy of Sciences, ul. M. Curie-Skłodowskiej 34, 41-819 Zabrze, Poland
Tamara Khalaf
Wolverhampton School of Sciences, Faculty of Science and Engineering, University of Wolverhampton, Wulfruna Street, Wolverhampton WV1 1LY, UK
Mariastella Scandola
Department of Chemistry ′G. Ciamician′ and National Consortium of Materials Science and Technology (INSTM, Bologna RU), Alma Mater Studiorum–Università di Bologna Via Selmi 2, 40126 Bologna, Italy
Maria Letizia Focarete
Department of Chemistry ′G. Ciamician′ and National Consortium of Materials Science and Technology (INSTM, Bologna RU), Alma Mater Studiorum–Università di Bologna Via Selmi 2, 40126 Bologna, Italy
Marek Kowalczuk
Wolverhampton School of Sciences, Faculty of Science and Engineering, University of Wolverhampton, Wulfruna Street, Wolverhampton WV1 1LY, UK
Iza Radecka
Wolverhampton School of Sciences, Faculty of Science and Engineering, University of Wolverhampton, Wulfruna Street, Wolverhampton WV1 1LY, UK
In recent years, there has been an increasing interest in oncolytic adenoviral vectors as an alternative anticancer therapy. The induction of an immune response can be considered as a major limitation of this kind of application. Significant research efforts have been focused on the development of biodegradable polymer poly-gamma-glutamic acid (γ-PGA)-based nanoparticles used as a vector for effective and safe anticancer therapy, owing to their controlled and sustained-release properties, low toxicity, as well as biocompatibility with tissue and cells. This study aimed to introduce a specific destructive and antibody blind polymer-coated viral vector into cancer cells using γ-PGA and chitosan (CH). Adenovirus was successfully encapsulated into the biopolymer particles with an encapsulation efficiency of 92% and particle size of 485 nm using the ionic gelation method. Therapeutic agents or nanoparticles (NPs) that carry therapeutics can be directed specifically to cancerous cells by decorating their surfaces using targeting ligands. Moreover, in vitro neutralizing antibody response against viral capsid proteins can be somewhat reduced by encapsulating adenovirus into γ-PGA-CH NPs, as only 3.1% of the encapsulated adenovirus was detected by anti-adenovirus antibodies in the presented work compared to naked adenoviruses. The results obtained and the unique characteristics of the polymer established in this research could provide a reference for the coating and controlled release of viral vectors used in anticancer therapy.
