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Poly-Gamma-Glutamic Acid (γ-PGA)-Based Encapsulation of Adenovirus to Evade Neutralizing Antibodies
Ibrahim R Khalil1,2, Martin P Khechara3, Sathishkumar Kurusamy4
1Wolverhampton School of Sciences, Faculty of Science and Engineering, University of Wolverhampton, Wulfruna Street, Wolverhampton WV1 1LY, UK. Ibrahim.khalil@wlv.ac.uk.
Abstract:
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.
Insights
Polymer-coated adenoviruses show promise for cancer therapy by reducing immune response. Poly-gamma-glutamic acid and chitosan nanoparticles effectively encapsulate adenovirus, enhancing targeted delivery and safety.
Area of Science:
- Biotechnology
- Nanomedicine
- Oncology
Background:
- Oncolytic adenoviral vectors are a promising anticancer therapy, but immune responses limit their effectiveness.
- Biodegradable poly-gamma-glutamic acid (γ-PGA)-based nanoparticles offer controlled release, low toxicity, and biocompatibility for drug delivery.
- Developing strategies to shield viral vectors from immune detection is crucial for improving cancer treatment efficacy.
Purpose of the Study:
- To develop a polymer-coated viral vector using poly-gamma-glutamic acid (γ-PGA) and chitosan (CH) for targeted cancer cell delivery.
- To evaluate the encapsulation efficiency and particle characteristics of adenovirus within γ-PGA-CH nanoparticles.
- To assess the ability of the polymer coating to reduce the neutralizing antibody response against the encapsulated adenovirus.
Main Methods:
- Adenovirus was encapsulated into γ-PGA-CH nanoparticles using the ionic gelation method.
- Encapsulation efficiency and particle size were determined.
- In vitro assays were performed to measure the detection of encapsulated adenovirus by anti-adenovirus antibodies compared to naked adenoviruses.
Main Results:
- Successful encapsulation of adenovirus into γ-PGA-CH nanoparticles with 92% efficiency and a particle size of 485 nm.
- The polymer coating significantly reduced the detection of adenovirus by neutralizing antibodies, with only 3.1% detected compared to naked adenoviruses.
- Demonstrated potential for targeted delivery and immune evasion of viral vectors.
Conclusions:
- γ-PGA-CH nanoparticles provide an effective method for encapsulating adenovirus, enhancing its potential as an anticancer therapeutic.
- The polymer coating shields adenovirus from neutralizing antibodies, mitigating a key limitation of viral vector therapy.
- This approach offers a valuable reference for the development of coated viral vectors for controlled release and improved anticancer efficacy.
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