Let There Be Light: Targeted Photodynamic Therapy Using High Aspect Ratio Plant Viral Nanoparticles

Abstract

The development of plant viral nanoparticles (VNP) loaded with different molecular versions of a photodynamic drug is described. Specifically, tobacco mosaic virus (TMV) and tobacco mild green mosaic virus (TMGMV) are developed as drug carriers that encapsulate the monocationic, dicationic, tricationic, and tetracationic versions of a porphyrin‐based photosensitizer drug (Zn‐Por). While TMV has been extensively explored for various nanotechnology applications, this is the first study investigating TMGMV for medical applications. Light‐activated cancer cell killing of Zn‐Por‐loaded VNPs is studied in vitro using melanoma and cervical cancer models. Native and nucleolin‐targeted VNP drug carriers are developed and their efficacy assessed. A fivefold increase in cancer cell killing is observed using nucleolin‐targeted TMV loaded with tricationic Zn‐Por and displaying the nucleolin‐specific F3 peptide.

Phthalocyanine–Virus Nanofibers as Heterogeneous Catalysts for Continuous‐Flow Photo‐Oxidation Processes

“…This geometry, which renders a negatively charged helix on the outer surface of the virus at pH above 4.5, can function as a well‐defined scaffold for unidimensional ensembles. TMV has been employed as drug delivery platform, as well as building block in different biohybrid arrays together with small functional molecules, or nanoparticles …”

Plant viral nanoparticles for packaging and in vivo delivery of bioactive cargos

“…Loading strategies and properties of PVNPs all combine to make PVNPs a versatile biological platform for various applications. They offer platforms with broad applications in energy transfer by mineralization of metal material (Thangavelu et al, ), light‐harvesting system by couplings with chromophores (Delor et al, ), sensing by displaying thousands of identical receptor peptides (Zang, Gerasopoulos, Brown, Culver, & Ghodssi, ), nanoreactors/biocatalyst by encapsulation of catalytic nanoparticles (A. Liu, de Ruiter, Maassen, & Cornelissen, ; A. Liu, Traulse, et al, ), and pesticide delivery system by loading herbicides (P. L. Chariou, Doga, et al, ; P. L. Chariou, Wang, et al, ; Chariou & Steinmetz, ). Medical approaches for utilizing PVNPs include therapeutic delivery, bioimaging, vaccine development, immunotherapy (Wang & Steinmetz, ), and tissue engineering (T. Liu et al, ).…”

“…For example, PEGylating and high aspect ratio of PVNPs increase circulation time and decrease their uptake by phagocytic cells that is critical for improved margination, and enhanced tumor homing and tissue penetration. In addition, genetic/chemical addition of ligands that bind to receptors overexpressed on particular cell types can increase cell specificity (P. L. Chariou, Doga, et al, ; P. L. Chariou, Wang, et al, ; Lee et al, ; Röder et al, ).…”

“…A PVNP‐based nanocarrier should package the cargo, and deliver it into the appropriate sites, cells and subcellular location in target cells. Nontargeted or targeted, PVNP have been developed as carriers of drugs (e.g., MTX) for chemotherapy (Lam et al, ), gold, and ruthenium for photothermal therapy, porphyrin‐based PS drugs (Zn‐Por) for PDT (P. L. Chariou, Doga, et al, ; P. L. Chariou, Wang, et al, ), and contrast agents for bioimaging. For example, in cancer therapy, nontargeted PVNP formulations owing to shape and size and the sometimes leaky vasculature of the tumor tissue can accumulate in tumor microenvironment in a highly variable process termed enhanced permeability and retention (Sandra, Khaliq, Sunna, & Care, ) (Figure c1).…”

Plant/Bacterial Virus-Based Drug Discovery, Drug Delivery, and Therapeutics

“…Zn-EpPor-loaded TMV particles showed enhanced cell killing efficacy compared to free Zn-EpPor molecules, which was attributed to the increased cellular uptake of photosensitizer as a result of their delivery within the TMV particles. Recently, the effect of photosensitizer’s charge on drug loading efficiency of TMV particles was investigated in a study where different zinc porphyrin (Zn-Por) formulations (monocationic (Zn-Por 1+ ), dicationic (Zn-Por 2+ ), tricationic (Zn-Por 3+ ), and tetracationic (Zn-Por 4+ )) were employed [233]. While the tricationic formulation demonstrated the highest loading efficiency (~600 molecules/TMV), the results were attributed to the combined effect of electrostatic and hydrophobic/hydrophilic interactions; higher positive charge was suggested to result in better stabilization of the photosensitizers inside TMV particles due to the electrostatic interactions with the deprotonated carboxylate residue of glutamic acid at pH 7.8.…”