Utilizing Viral Nanoparticle/Dendron Hybrid Conjugates in Photodynamic Therapy for Dual Delivery to Macrophages and Cancer Cells

Abstract

Photodynamic therapy (PDT) is a promising avenue for greater treatment efficacy of highly resistant and aggressive melanoma. Through photosensitizer attachment to nanoparticles, specificity of delivery can be conferred to further reduce potential side effects. While the main focus of PDT is the destruction of cancer cells, additional targeting of tumor-associated macrophages also present in the tumor microenvironment could further enhance treatment by eliminating their role in processes such as invasion, metastasis, and immunosuppression. In this study, we investigated PDT of macrophages and tumor cells through delivery using the natural noninfectious nanoparticle cowpea mosaic virus (CPMV), which has been shown to have specificity for the immunosuppressive subpopulation of macrophages and also targets cancer cells. We further explored conjugation of CPMV/dendron hybrids in order to improve the drug loading capacity of the nanocarrier. Overall, we demonstrated effective elimination of both macrophage and tumor cells at low micromolar concentrations of the photosensitizer when delivered with the CPMV bioconjugate, thereby potentially improving melanoma treatment.

Plant viruses and bacteriophages for drug delivery in medicine and biotechnology

“…CPMV modified with a corona of negatively charged dendrons was used to complex and load positively charged PDT agents. This VNP-synthetic hybrid material was effective in killing both a melanoma cell line as well as macrophages – the combined efficacy on cancer cells and tumor-associated macrophages could be a powerful strategy for cancer therapy [36]. …”

Photodynamic Therapy and the Biophysics of the Tumor Microenvironment

“…However, they also have affinity for vimentin, which is overexpressed in certain epithelial cancers, including prostate cancer, gastrointestinal tumors, breast cancer and lung cancer . According to the results of the study, the PS‐CPMV nanoconstruct (zinc ethynylphenyl porphyrin conjugated CPMV/ dendron hybrid) was effective on both cancer cells and macrophages but did not favor the M2 subpopulation, despite previous work suggesting that CPMV has a preference for M2‐polarized macrophages .…”

Photon Management through Virus‐Programmed Supramolecular Arrays

“…Purified CPMV virions were stored in 0.1 m potassium phosphate buffer pH 7.0 at 4 °C. CPMV was covalently modified to display generation 3 carboxylate‐terminated dendrons to yield CPMV* using methods as we previously described . CPMV and CPMV* were characterized by transmission electron microscopy, UV–vis spectroscopy, native, and denaturing gel electrophoresis.…”

“…The coassembly of crystalline arrays of viruses and dendrimers has been previously demonstrated, and the system has been proven to be robust and versatile. Here, we also considered dendron‐conjugated CPMV formulations featuring 3‐arm carboxylate‐terminated dendrons; denoted as CPMV* (Figure d,e) and prepared using Cu(I)‐catalyzed azide‐alkyne cycloaddition coupling methods as we previously described . The CPMV* formulation displays a corona of negatively charged dendrons on its already negatively charged surface; but zeta potential measurements do not show an overall increase in negative charge, with ζ = −8 mV.…”