Hypoxia-Responsive Aggregation of Gold Nanoparticles for Near-Infrared-II Photoacoustic Imaging-Guided Enhanced Radiotherapy

Abstract

By directly harming cancer cells, radiotherapy (RT) is a crucial therapeutic approach for the treatment of cancers. However, the efficacy of RT is reduced by the limited accumulation and short retention time of the radiosensitizer in the tumor. Herein, we developed hypoxia-triggered in situ aggregation of nanogapped gold nanospheres (AuNNP@PAA/NIC NPs) within the tumor, resulting in second nearinfrared window (NIR-II) photoacoustic (PA) imaging and enhanced radiosensitization. AuNNP@PAA/NIC NPs demonstrated increased accumulation and retention in hypoxic tumors, mainly due to the hypoxia-triggered aggregation. After aggregation of AuNNP@PAA/ NIC NPs, the absorption of the system extended from visible light to NIR-II light owing to the plasmon coupling effects between adjacent nanoparticles. Compared to the normoxic tumor, the PA intensity at 1200 nm in the hypoxic tumor increased from 0.42 to 1.88 at 24 h postintravenous injection of AuNNP@PAA/NIC NPs, leading to an increase of 4.5 times. This indicated that the hypoxic microenvironment in the tumor successfully triggered the in situ aggregation of AuNNP@PAA/NIC NPs. The in vivo radiotherapeutic effect demonstrated that this hypoxia-triggered in situ aggregation of radiosensitizers significantly enhanced radiosensitization and thus resulted in superior cancer radiotherapeutic outcomes.

Deoxygenation-Promoted Aggregation-Induced TADF–RTP Dual Emission for High-Contrast Channel-Selectable Hypoxia Probing

“…This trend is consistent with the gradual appearance of a signal of several thousand nanometers in the DLS spectrum (Figure S26). This cross-linking process reflects that deoxygenation is beneficial for eliminating the barrier between dissolved oxygen and the initial aggregates, − further inhibiting the nonradiative processes and resulting in high-contrast changes for TADF and RTP. The fwhm of the band centered at 590 nm is 175 nm, signifying a broad spectral characteristic that is favorable for selecting different channels for bioimaging.…”

Biomarker-driven molecular imaging probes in radiotherapy

“…TEM images clearly indicated distinctive aggregation of nanoparticles when the incubation oxygen level dropped from 21% or 10%, to 1%. In addition, a 4.5-fold increase in the photoacoustic intensity in the in-vivo tumor area was credited to hypoxia-induced aggregation of probes, interestingly, an improvement in the radiotherapeutic efficacy by these gold nanoparticles suggested that they could be radiosensitizers 122 .…”

Photoacoustic imaging for investigating tumor hypoxia: a strategic assessment

“…Mice with the targeted contrast agent had a significantly increased signal for HbO 2 . Many studies used metallic nanomaterial and PAI to guide radio/chemotherapy [22] [101,102]. For example, polyacrylic acid-coated superparamagnetic iron oxide nanoparticles were modified to be cisplatin-loaded, poly-dopamine coated and GE11 peptide coated, creating GE11-PDA-Pt@USPIOS.…”

“…This study showed strong PA signals due to the accumulation of these agents whereas, the control mice with just AuNRs showed ambiguous signaling 110 . A clever implementation of the overexpression of nitroreductases in tumor hypoxia used Au nanoparticles that aggregated (polymerized) in the presence of the hypoxic environment 102 . After aggregation, the plasmon coupling effects between adjacent nanoparticles extended system absorption from the visible into the NIR-II light range.…”