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PH-responsive targeted gold nanoparticles for in vivo photoacoustic imaging of tumor microenvironments.

ABSTRACT: The acidic microenvironment of tumor tissues has been proven to be a major characteristic for differentiation from normal tissues, thereby providing a desirable target for both disease diagnosis and functional imaging. We herein introduce a way to endow gold nanoparticles with aggregation behaviour induced by pH tuning. The nanoparticle surface was modified with two thiol conjugate molecules, which could smartly stabilize it at the pH of blood and normal tissues but induce aggregation in response to the acidic extracellular pH in tumor. The surface conjugate molecule composition effect was studied systematically, and at the optimal surface conjugate molecule composition, a pH-responsive active tumor-targeting c(RGDyk)-MHDA/LSC@AuNP nanoprobe was successfully obtained and showed a significantly enhanced contrast effect for both in vitro and in vivo photoacoustic (PA) imaging. Intravenous administration of our nanoprobe to U87MG tumor-bearing nude mice showed PA imaging contrasts almost 3-fold higher than those for the blocking group. Quantitative biodistribution data revealed that 9.7 μg g^-1 of nanoprobe accumulated in the U87MG tumor 4 h post-injection. These findings might provide an effective strategy for developing new classes of intelligent and biocompatible contrast agents with a high efficiency for PA imaging and PA imaging-guided cancer therapy.

SUBMITTER: Li S

PROVIDER: S-EPMC9473232 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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pH-responsive targeted gold nanoparticles for <i>in vivo</i> photoacoustic imaging of tumor microenvironments.

Li Shiying S Lui Kwok-Ho KH Tsoi Tik-Hung TH Lo Wai-Sum WS Li Xin X Hu Xuesen X Chi-Shing Tai William W Hiu-Ling Hung Clara C Gu Yan-Juan YJ Wong Wing-Tak WT

Nanoscale advances 20181213 2

The acidic microenvironment of tumor tissues has been proven to be a major characteristic for differentiation from normal tissues, thereby providing a desirable target for both disease diagnosis and functional imaging. We herein introduce a way to endow gold nanoparticles with aggregation behaviour induced by pH tuning. The nanoparticle surface was modified with two thiol conjugate molecules, which could smartly stabilize it at the pH of blood and normal tissues but induce aggregation in respons ...[more]

PMID: 36132235

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Project description:Photoacoustic tomography (PAT) combines optical and acoustic imaging to generate high-resolution images of microvasculature. Inherent sensitivity to hemoglobin permits PAT to image blood vessels but precludes discriminating neovascular from maturing microvasculature. ?(v)?(3)-Gold nanobeacons (?(v)?(3)-GNBs) for neovascular molecular PAT were developed, characterized, and demonstrated in vivo using a mouse Matrigel-plug model of angiogenesis. PAT results were microscopically corroborated with fluorescent ?(v)?(3)-GNB localization and supporting immunohistology in Rag1(tm1Mom) Tg(Tie-2-lacZ)182-Sato mice. ?(v)?(3)-GNBs (154 nm) had 10-fold greater contrast than blood on an equivolume basis when imaged at 740 nm to 810 nm in blood. The lowest detectable concentration in buffer was 290 nM at 780 nm. Noninvasive PAT of angiogenesis using a 10-MHz ultrasound receiver with ?(v)?(3)-GNBs produced a 600% increase in signal in a Matrigel-plug mouse model relative to the inherent hemoglobin contrast pretreatment. In addition to increasing the contrast of neovessels detected at baseline, ?(v)?(3)-GNBs allowed visualization of numerous angiogenic sprouts and bridges that were undetectable before contrast injection. Competitive inhibition of ?(v)?(3)-GNBs with ?(v)?(3)-NBs (no gold particles) almost completely blocked contrast enhancement to pretreatment levels, similar to the signal from animals receiving saline only. Consistent with other studies, nontargeted GNBs passively accumulated in the tortuous neovascular but provided less than half of the contrast enhancement of the targeted agent. Microscopic studies revealed that the vascular constrained, rhodamine-labeled ?(v)?(3)-GNBs homed specifically to immature neovasculature (PECAM(+), Tie-2(-)) along the immediate tumor periphery, but not to nearby mature microvasculature (PECAM(+), Tie-2(+)). The combination of PAT and ?(v)?(3)-GNBs offered sensitive and specific discrimination and quantification of angiogenesis in vivo, which may be clinically applicable to a variety of highly prevalent diseases, including cancer and cardiovascular disease.

Dataset Information

PH-responsive targeted gold nanoparticles for in vivo photoacoustic imaging of tumor microenvironments.

Publications

pH-responsive targeted gold nanoparticles for <i>in vivo</i> photoacoustic imaging of tumor microenvironments.

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