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Nanoparticle-mediated photothermal therapy (PTT) is a promising strategy for cancer treatment; however, nanoparticle instability and lack of precise imaging tools for real-time temperature monitoring during therapy and nanoparticle tracking have hindered investigations in animal models. To address these critical issues, we present a theranostic platform that seamlessly integrates armored core–gold nanostar (AC-GNS)–mediated PTT with full-view photoacoustic computed tomography (PACT), enabling nanoparticle tracking and real-time imaging-guided PTT in deep tissues. The AC-GNS platform delivered exceptional photostability and thermal resilience beyond those of conventional nanoparticles while serving as a high-performance contrast agent for PACT and a photothermal transducer for PTT. Integrating AC-GNS–mediated PTT with noninvasive PACT enabled whole-body nanoparticle tracking, PTT treatment monitoring via thermal imaging, and thermal dose determination, culminating in a 100% survival rate in a murine bladder cancer model without long-term treatment-related toxicity. This theranostic platform lays the foundation for broader research applications and provides opportunities for advancing solid tumor treatment and response assessment research.
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Self-assembled peptide-dye nanostructures for in vivo tumor imaging and photodynamic toxicity
Abstract We report noncovalent assemblies of iRGD peptides and methylene blue dyes via electrostatic and hydrophobic stacking. These resulting nanomaterials could bind to cancer cells, image them with photoacoustic signal, and then treat them via photodynamic therapy. We first assessed the optical properties and physical properties of the materials. We then evaluated their utility for live cell targeting, in vivo imaging, and in vivo photodynamic toxicity. We tuned the performance of iRGD by adding aspartic acid (DD) or tryptophan doublets (WW) to the peptide to promote electrostatic or hydrophobic stacking with methylene blue, respectively. The iRGD-DD led to 150-nm branched nanoparticles, but iRGD-WW produced 200-nm nano spheres. The branched particles had an absorbance peak that was redshifted to 720 nm suitable for photoacoustic signal. The nanospheres had a peak at 680 nm similar to monomeric methylene blue. Upon continuous irradiation, the nanospheres and branched nanoparticles led to a 116.62% and 94.82% increase in reactive oxygen species in SKOV-3 cells relative to free methylene blue at isomolar concentrations suggesting photodynamic toxicity. Targeted uptake was validated via competitive inhibition. Finally, we used in vivo bioluminescent signal to monitor tumor burden and the effect of for photodynamic therapy: The nanospheres had little impact versus controls (p = 0.089), but the branched nanoparticles slowed SKOV-3 tumor burden by 75.9% (p < 0.05).
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- Award ID(s):
- 1845683
- PAR ID:
- 10501671
- Publisher / Repository:
- Springer Nature
- Date Published:
- Journal Name:
- npj Imaging
- Volume:
- 2
- Issue:
- 1
- ISSN:
- 2948-197X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
-
Accepted Manuscript
- Journal Article:
- https://doi.org/10.1038/s44303-024-00008-4
