Chemically Tuned Virus Like Particles: From Cancer Therapy to Targeted Delivery

In recent years, nanoparticle-based therapeutics have been increasingly applied in broad range of clinical applications from diagnosis to treatment of many diseases such as cancer, diabetes and neurodegenerative disorders. A wide range of synthetic and naturally occurring materials such as polymers, metal oxides, silicate, liposome, and carbon nanotubes have been developed to overcome some of the key barriers in free therapeutics including intracellular trafficking, cell/tissue targeting, poor biodistribution, and low efficiency. However, despite all achievements in creating these nanomaterials with different chemical and physical properties such as size, shape and surface properties, developing a nanoparticle to surmount these limitations all in one is a big challenge. Virus like particle (VLP) as protein-based nanomaterials that closely mimic the highly symmetrical and polyvalent conformation of viruses while lack the viral genomes have emerged as a solution for these limitations. Their unique features such as high biocompatibility, biodegradability, monodisperisty, intrinsic immunogenicity, and safety combined with interior and exterior modification capability offer new tool to scientists for careful design and engineering of multi-component therapeutic agent with intended biological behavior and pharmacological profiles. Herein, various chemistry strategies are introduced in combination with biology and immunology to turn virus like particle to a favorable engineered biomaterial for several functions such as cancer therapy and intracellular delivery. We showed how by modifying surface of VLP Qβ with NIR organic molecule we can make a highly efficient and stable photothermal agent that can cause thermal ablation of tumor while simultaneously activating the immune response. We found this immunophotothermal agent, suppress primary tumor, control metastasis, and prolong survival time in mice bearing breast cancer. We also addressed one of the biggest challenges in biologic delivery which is direct delivery of therapeutic cargo into cell cytoplasm. Using organic chemistry we designed a cytosolic targeting linker that when attached to surface of VLP Qβ, helps to escape endosomes and be released into cytoplasm, Moreover, this proteinaceous material is shown to have a great potential in combination with other materials such as metal organic framework to construct a multimodal cancer therapeutic agent enabling delivering mulit therapeutic agents such as immunotherapeutic drugs while taking advantage of all unique features of virus like particles. These works clearly show the significant potential of VLP in design and modification of new therapeutic platform.