Analysis of Targeted Viral Protein Nanoparticles Delivered to HER2+ Tumors

Abstract

The HER2+ tumor-targeted nanoparticle, HerDox, exhibits tumor-preferential accumulation and tumor-growth ablation in an animal model of HER2+ cancer. HerDox is formed by non-covalent self-assembly of a tumor targeted cell penetration protein with the chemotherapy agent, doxorubicin, via a small nucleic acid linker. A combination of electrophilic, intercalation, and oligomerization interactions facilitate self-assembly into round 10–20 nm particles. HerDox exhibits stability in blood as well as in extended storage at different temperatures. Systemic delivery of HerDox in tumor-bearing mice results in tumor-cell death with no detectable adverse effects to non-tumor tissue, including the heart and liver (which undergo marked damage by untargeted doxorubicin). HER2 elevation facilitates targeting to cells expressing the human epidermal growth factor receptor, hence tumors displaying elevated HER2 levels exhibit greater accumulation of HerDox compared to cells expressing lower levels, both in vitro and in vivo. Fluorescence intensity imaging combined with in situ confocal and spectral analysis has allowed us to verify in vivo tumor targeting and tumor cell penetration of HerDox after systemic delivery. Here we detail our methods for assessing tumor targeting via multimode imaging after systemic delivery.

Biomedical Applications of Translational Optical Imaging: From Molecules to Humans

“…This had to be undertaken from the ground up, as there was no commercial offering to even constitute a platform for building on. We developed an advanced multimode optical imaging capability in a stand-alone system that enables functional mesoscopic imaging (whole-body or endoscopic imaging with microscopic resolution) of small animals in vivo and provides for quantitative, dynamic, and functional monitoring of chemo-and nanoconstruct therapy [97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113][114][115]. Many currently available imaging approaches have been applied to preclinical studies of cancer, stem cells, and pharmaceutical outcomes.…”

“…Multimode assessment of nanoconstructs and HerGa chemotherapy (top) and application and capabilities of each imaging mode in the multimode panel (bottom)[100][101][102][103][104][105][106][107][108][109][110][111][112][113][114][115].…”