Biocompatible Polymers for Oncolytic Virus Delivery
Biocompatible Polymer System
Biocompatible polymers are extremely useful carriers with excellent blood compatibility and structural integrity, which can be used in a wide range of drug delivery systems. The interaction between protein and biomaterial surfaces is critical for the design of biocompatible materials. The principles for designing biocompatible polymer materials are based on passivation of the polymer surfaces to minimize non-specific protein interaction or decoration of polymer surfaces with biomolecules to induce specific protein adsorption and cell responses. Physiologically stable and optionally bioreversible bonds are formed to generate targeted particles by defined and precise chemical reactions that are compatible with the structural integrity and biological functions of both vector particles and ligand. The biocompatibility approach is robust, gentle, and straightforward. Biocompatible polymer coating could be useful for masking the surface of other microorganisms to interact with a biological system and even cells for diverse applications in medicine such as clinical gene therapy and also for vaccination potentially.
Biocompatible Polymers for Oncolytic Virus Delivery
Oncolytic viruses (OVs) could become the most powerful and selective cancer therapies. However, the limited transport of OVs into and throughout tumors following intravenous injection means their clinical administration is often restricted to direct intratumorally dosing. Biocompatible polymer strategies most commonly utilize polymers intending to reduce specific and unspecific interactions, typically based on a polyethylene glycol (PEG) or poly-[N-(2-hydroxypropyl) methacrylamide] (PHPMA) polymer backbone, to modify viruses covalently or noncovalently or to shield viruses chemically. These hydrophilic polymer coating can be chemically cross-linked to therapeutic viruses with protection from the immune system and antibody recognition. Polymer-coated viruses overcome their instability in serum and maintain enough level of infection to achieve systemic delivery of OVs.
Fig.1 Approaches to the surface modification of Ads. (Kasala, 2016)
Much of the work to characterize the impact of polymer coating on clearance, infection and blood stability of OVs are performed on viruses based on adenovirus (Ad). Surface masking of Ad using polymers based on PEG or PHPMA should provide a physical barrier to prevent all forms of receptor-mediated infection. PEGylation or PHPMA of Ad5 has been reported to abolish the infection of polymer-coated Ad in vitro and to reduce the binding of neutralizing antibodies both in vitro and in vivo. Notably, it is shown that PEGylation reduces anti-Ad5 adaptive immune response induction with a reduction in the number of cytotoxic T lymphocytes (CTLs) detected.
Interestingly, a further study report that the oncolytic adenovirus delivered by the polymer through systemic injection has negligible hepatotoxicity and enhances tumor growth suppression. The lower rate of blood clearance and higher targeting affinity of the Ad-polymer complexes raises the probability of delivery into target disease tissue with minimal diffusion into normal cells. Therefore, the potential system of oncolytic Ad complexed with novel biocompatible polymers has become critical to delivering a polymer shielded OV effectively to target tumor sites via systemic delivery. To date, these preclinically promising Ad modification approaches have still be not progressed into the clinics.
Polymer-coating technology appears to provide a platform for the development of targeted oncolytic virus therapy in a range of disease settings. In terms of our extensive experience in the oncolytic virus construction and oncolytic virus engineering, Creative Biolabs has built an advanced OncoVirapy™ platform to offer the best services for our global customers' projects.
Reference
- Kasala, D.; Yun, C.O. Polymer-Anchored Adenovirus as a Therapeutic Agent for Cancer Gene Therapy. In Adenoviral Vectors for Gene Therapy. 2016, (pp. 707-737). Academic Press.