Viruses-Nanoparticles Conjugates Services

Virus-nanoparticle complexes refer to the attachment or growth of nanoparticles outside or inside the viral protein capsid. The complex has great application potential in the fields of drug delivery, gene therapy and material manufacturing. CD Bioparticles provides an integrated platform covering the development and manufacture of virus-nanoparticle conjugates from preclinical research to commercialization stage. We are committed to providing a wide range of services, including polymer synthesis, characterization, purification and isolation, bioconjugation, and side/end group modification.

Introduction to Viruses-Nanoparticles Conjugates

It is well known that virus-like particles (VLPs) have become emerging tools in the field of nanomedicine due to their monodispersity, well-defined shape and size, and precise positioning for drug, targeting ligand, and polymer conjugation. Non-infectious VLPs have been applied in the fields of tumor targeting, drug delivery, immunotherapy and imaging, and the research on gene delivery has also received extensive attention. However, overcoming immune surveillance remains a challenge since VLPs activate innate and humoral immune responses. For example, studies using adeno-associated virus have shown that repeated injections may limit efficacy and may trigger an adverse inflammatory immune response. These effects can be mitigated by covalently coupling polymers to the capsid surface. In recent years, the method of attaching or growing synthetic polymers on or inside viral protein capsids has opened up completely new research ideas.

Figure 1. Viruses-Nanoparticles Conjugates.

Virus-polymer conjugated materials have shown remarkable performances, which benefit from the unique properties of viruses and polymers, as well as the controllable and stable integration of functional molecules through covalent chemistry. In fact, researchers have found that by combining VLPs with polymers, their physical properties can be dramatically altered. The introduction of polymers can enhance the thermal stability of virus particles, especially has an important impact on the stability of secondary protein structures, and the application of cross-linking strategies further improves the stability of higher-order protein structures. In addition, another feature of virus-polymer composites is the controllable biological interaction. The advantage of using VLPs is that the position of active residues can be determined with atomic-level precision, allowing the spatial structure of substituents to be defined on the surface.

The specific features of viruses-nanoparticles conjugates include:

• Precise delivery: Since the virus itself has an inherent affinity for specific cell types, it has targeted and precise delivery capabilities. By attaching nanoparticles to the surface of viruses, these complexes can be engineered to selectively deliver therapeutics, genes or drugs to specific tissues or cells.
• Enhanced stability: Nanoparticles can increase the stability of viruses, protecting them from degradation by enzymes or harsh environmental conditions such as changes in temperature and pH. This stability extends the lifespan and efficacy of the complex.
• Controlled assembly: Viruses have a well-defined structure that can be used to precisely assemble nanoparticle-functionalized viral vectors. This arrangement can enhance the stability of the structure and control the display of the targeting ligand.
• Gene delivery: Viruses are natural gene carriers that facilitate gene delivery into host cells. By combining nanoparticles with viral vectors, researchers can increase the efficiency and specificity of gene delivery for therapeutic purposes.
• Immune interference: Modification of the surface of viruses with nanoparticles can alter their interaction with the immune system. This modification may help the complexes avoid immune detection and clearance, thereby prolonging their presence in the body and enhancing therapeutic efficacy.
• Customizable properties: Nanoparticles offer a variety of tunable properties such as size, shape, surface charge, and functionalization. These properties can be exploited to optimize the behavior of virus-nanoparticle complexes for specific applications.
• Biocompatibility and safety: Compared with traditional viral vectors or nanoparticles alone, rationally designed virus-nanoparticle complexes can exhibit better biocompatibility and lower toxicity.
• Modulated Release: Nanoparticles can be designed to encapsulate therapeutic substances and release them in a controlled manner. When combined with viruses, these systems are able to provide controlled and sustained release of therapeutic payloads.
• Tissue Penetration: Combining viral infection mechanisms with the properties of nanoparticles enables better penetration of biological barriers, such as the blood-brain barrier, resulting in improved drug delivery to target tissues.

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• Long polymer chain grafting scheme

The surface grafting method is mainly applied to polymer attachment on the outer surface of VLPs, that is, attaching long polymer chains directly to the surface. Currently, the more common approach is to perform conjugation on surface-exposed lysine or tyrosine residues. With rich experience in polymer modification, CD Bioparticles' virus-polymer conjugation technology mainly supports customized services for bacteriophage Qβ, phage MS2 and tobacco mosaic virus (TMV). We provide our clients with a tailor-made approach to meet their needs.

• Grafting Strategies of Small Molecule Initiators

To increase the yield of surface polymers and better control the polymerization process, a modification strategy of more densely loaded small-molecule initiators on the surface was employed. These initiators are then used in the subsequent polymerization step, which in principle leads to the formation of a controllable synthetic shell on the outer surface. Drawing on our expertise in polymer technology and PEG research, CD Bioparticles offers PEG glycosylation solutions for a variety of viruses to improve their pharmacokinetic and pharmacodynamic properties.

The applications of viruses-nanoparticles conjugates include:

Viral capsids have been widely used in medicine because of their superior nanomaterial properties. They are inherently designed to safely house genomic material and allow stable transport in harsh environments. In addition, the unique monodisperse size and volume properties of viral capsids are also attractive. This precise volumetric feature allows the viral capsid to more precisely regulate the stoichiometry of potential catalytic reactions, as well as precisely control parameters such as drug dosage during drug delivery. More importantly, viral nanoparticles are biodegradable, which gives viral capsids a clear advantage over non-degradable materials. The protein capsid itself is well tolerated and, when properly functionalized, can achieve clinically useful circulating half-lives.

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Reference

1. Gibson, M.I. et al.; Engineering cell durfaces bycovalent grafting of synthetic polymers to metabolically-labeled glycans. ACS Macro Lett. 2018, 7: 1289-1294.