Computationally Guided Photothermal Tumor Therapy Using Long-Circulating Gold Nanorod Antennas

TLDR

Plasmonic nanomaterials can markedly improve cancer ablation specificity by homing to tumors intravenously and acting as antennas for externally applied energy. The study presents an integrated approach that combines multimodal nanomaterial optimization with computational irradiation protocol development to enhance plasmonic therapy. After intratumoral or intravenous administration, PEG‑protected gold nanorods’ biodistribution data from X‑ray computed tomography or ex vivo spectrometry are fused with four‑dimensional computational heat‑transport modeling to predict photothermal heating during irradiation. PEG‑protected gold nanorods display superior spectral bandwidth, photothermal heat generation, a ~17‑hour circulation half‑life, and ~2‑fold higher X‑ray absorption than clinical iodine contrast, and in pilot studies a single intravenous injection eradicated all irradiated human xenograft tumors in mice, underscoring the potential of computationally guided nanotherapeutic design for ultraselective tumor ablation.

Abstract

Plasmonic nanomaterials have the opportunity to considerably improve the specificity of cancer ablation by i.v. homing to tumors and acting as antennas for accepting externally applied energy. Here, we describe an integrated approach to improved plasmonic therapy composed of multimodal nanomaterial optimization and computational irradiation protocol development. We synthesized polyethylene glycol (PEG)-protected gold nanorods (NR) that exhibit superior spectral bandwidth, photothermal heat generation per gram of gold, and circulation half-life in vivo (t(1/2), approximately 17 hours) compared with the prototypical tunable plasmonic particles, gold nanoshells, as well as approximately 2-fold higher X-ray absorption than a clinical iodine contrast agent. After intratumoral or i.v. administration, we fuse PEG-NR biodistribution data derived via noninvasive X-ray computed tomography or ex vivo spectrometry, respectively, with four-dimensional computational heat transport modeling to predict photothermal heating during irradiation. In computationally driven pilot therapeutic studies, we show that a single i.v. injection of PEG-NRs enabled destruction of all irradiated human xenograft tumors in mice. These studies highlight the potential of integrating computational therapy design with nanotherapeutic development for ultraselective tumor ablation.