Plant Viral Nanoparticle Conjugated with Anti-PD-1 Peptide for Ovarian Cancer Immunotherapy

Immunotherapy holds tremendous potential in cancer therapy, in particular, when treatment regimens are combined to achieve synergy between pathways along the cancer immunity cycle. In previous works, we demonstrated that in situ vaccination with the plant virus cowpea mosaic virus (CPMV) activates and recruits innate immune cells, therefore reprogramming the immunosuppressive tumor microenvironment toward an immune-activated state, leading to potent anti-tumor immunity in tumor mouse models and canine patients. CPMV therapy also increases the expression of checkpoint regulators on effector T cells in the tumor microenvironment, such as PD-1/PD-L1, and we demonstrated that combination with immune checkpoint therapy improves therapeutic outcomes further. In the present work, we tested the hypothesis that CPMV could be combined with anti-PD-1 peptides to replace expensive antibody therapies. Specifically, we set out to test whether a multivalent display of anti-PD-1 peptides (SNTSESF) would enhance efficacy over a combination of CPMV and soluble peptide. Efficacy of the approaches were tested using a syngeneic mouse model of intraperitoneal ovarian cancer. CPMV combination with anti-PD-1 peptides (SNTSESF) resulted in increased efficacy; however, increased potency against metastatic ovarian cancer was only observed when SNTSESF was conjugated to CPMV, and not added as a free peptide. This can be explained by the differences in the in vivo fates of the nanoparticle formulation vs. the free peptide; the larger nanoparticles are expected to exhibit prolonged tumor residence and favorable intratumoral distribution. Our study provides new design principles for plant virus-based in situ vaccination strategies.

Viral Nanoparticle System: An Effective Platform for Photodynamic Therapy

Photodynamic therapy (PDT) is a promising therapy due to its efficiency and accuracy. The photosensitizer is delivered to the target lesion and locally activated. Viral nanoparticles (VNPs) have been explored as delivery vehicles for PDT in recent years because of their favorable properties, including simple manufacture and good safety profile. They have great potential as drug delivery carriers in medicine. Here, we review the development of PDT photosensitizers and discuss applications of VNP-mediated photodynamic therapies and the performance of VNPs in the treatment of tumor cells and antimicrobial therapy. Furthermore, future perspectives are discussed for further developing novel viral nanocarriers or improving existing viral vectors.

Protein-based nanoplatform for detection of tumorigenic polyps in the colon via noninvasive mucosal routes

The use of nanoparticulate systems to diagnose and treat tumors has gained momentum with the rapid development of nanomedicine. Many nanotheranostics fail due to insufficient bioavailability and low accumulation at the tumor site, resulting in undesirable side effects. We describe the use of an engineered hepatitis E viral nanoparticle (HEVNP) with enhanced bioavailability, tissue retention and mucosal penetration capacities. HEVNP is a modular nanocapsule that can encapsulate heterologous nucleotides, proteins and inorganic metals, such as ferrite oxide nanoparticles. Additionally, the exterior protruding arms of HEVNP is composed of loops that are used for chemical coupling of targeting and therapeutic peptides. We propose the use of HEVNP to target colorectal cancer (i.e., polyps) with imaging-guided delivery using colonoscopy.

Passive cancer targeting with a viral nanoparticle depends on the stage of tumorigenesis

Tumor targeting with nanoparticles is a promising strategy for cancer diagnosis and treatment, especially drug delivery to solid tumors. Previous studies mainly focused on nanoparticle design to improve their targeting...

Affinity of plant viral nanoparticle potato virus X (PVX) towards malignant B cells enables cancer drug delivery

Plant vital nanoparticle PVX shows a binding affinity towards malignant B cells and traffics to metastatic lymphoma sites in mice challenged with B cell lymphoma, thus enabling NHL-specific drug delivery.

The unique potency of Cowpea mosaic virus (CPMV) in situ cancer vaccine

Plant viral nanoparticle CPMV outperforms other icosahedral viruses as an in situ vaccine for cancer immunotherapy.

Cowpea mosaic virus (CPMV) as a carrier vehicle for antimalarial drugs, modification and application

Globally more than 45% of the population is under the risk of malaria infection. In this presented work, three different compounds have been tested as anti-malarial agents with and without conjugation to the external surface of Cowpea mosaic virus (CPMV). The particle developed as a carrier of ferrocene (Fc) due to the resistance to commercially available antimalarial drugs. CPMV-Fc conjugate, in which 174 molecules are covalently bound to external surface carboxylates of the viral nanoparticle (VNP), shows the greatest inhibition toward proliferation of plasmodium falciparum compared to free ferrocene which has no activity as antimalarial agent. Fc also enhanced the activity of two different compounds of 4-aminochloroqunoline derivatives 3-((7chloroquinolin-4-yl) amino) propionic acid CQp and (7-chloroquinolin-4-yl) alanine CQ-ala, after its conjugation to CPMV-CQp and CPMV-CQ-ala in 82 and 134 molecules per particle respectively to give CPMV-CQ-p-Fc and CPMV-CQ-ala-Fc. The activity of each conjugated ferrocene has been evaluated with and without using biological material. In the case of biological material these compounds have been tested against both chloroquine sensitive strain 3D7 and chloroquine resistance strain Dd2 using the chloroquine as a standard antimalarial drug. The CPMV conjugate is targeted to the food vacuole parasite of the plasmodium falciparum cell, where the pH is dropped, drug carrier is degraded and the drug released.