Preparation of near-infrared photoacoustic imaging and photothermal treatment agent for cancer using a modifiable acid-triggered molecular platform.

Ratiometric near-infrared fluorescent pH probes with various pKa values were innovatively designed and synthesized based on cyanine with a diamine moiety. The photochemical properties of these probes were thoroughly evaluated. Among the series, IR-PHA exhibited an optimal pKa value of approximately 6.40, closely matching the pH of cancerous tissues. This feature is particularly valuable for real-time pH monitoring in both living cells and living mice. Moreover, when administered intravenously to tumor-bearing mice, IR-PHA demonstrated rapid and significant enhancement of near-infrared fluorescence and photoacoustic signals within the tumor region. This outcome underscores the probe's exceptional capability for dual-modal cancer imaging utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) modalities. Concurrently, the application of a continuous-wave near-infrared laser efficiently ablated cancer cells in vivo, attributed to the photothermal effect induced by IR-PHA. The results strongly indicate that IR-PHA is well-suited for NIRF/PA dual-modality imaging and photothermal therapy of tumors. This makes it a promising candidate for theranostic applications involving small molecules.

Rechargeable Afterglow Nanotorches for In Vivo Tracing of Cell-Based Microrobots.

As one of the self-luminescence imaging approaches that require pre-illumination instead of real-time light excitation, afterglow luminescence imaging has attracted increasing enthusiasm to circumvent tissue autofluorescence. In this work, we developed organic afterglow luminescent nanoprobe (nanotorch), which could emit persistent luminescence more than 10 days upon single light excitation. More importantly, the nanotorch could be remote charged by 660 nm light in a non-invasive manner, which showed great potential for real-time tracing the location of macrophage cell-based microrobots.

H2 O2 -Responsive NIR-II AIE Nanobomb for Carbon Monoxide Boosting Low-Temperature Photothermal Therapy.

Low-temperature photothermal therapy (PTT), which circumvents the limitations of conventional PTT (e.g., thermotolerance and adverse effects), is an emerging therapeutic strategy which shows great potential for future clinical applications. The expression of heat shock proteins (HSPs) can dramatically impair the therapeutic efficacy of PTT. Thus, inhibition of HSPs repair and reducing the damage of nearby normal cells is crucial for improving the efficiency of low-temperature PTT. Herein, we developed a nanobomb based on the self-assembly of NIRII AIE polymer PBPTV and carbon monoxide (CO) carrier polymer mPEG(CO). This smart nanobomb can be exploded in a tumor microenvironment in which hydrogen peroxide is overexpressed and release CO into cancer cells to significantly inhibit the expression of HSPs and hence improve the antitumor efficiency of the low-temperature PTT.

In Vivo Near-Infrared Fluorescence and Photoacoustic Dual-Modal Imaging of Endogenous Alkaline Phosphatase.

Alkaline phosphatase (ALP) is distributed widely in living organisms and is an important biomarker closely related to many physiological and pathological processes. However, in vivo real-time detection of ALP remains a significant challenge. Herein, we developed a turn-on molecular probe (denoted as LET-3) to visualize ALP activity in tumor tissues through near-infrared fluorescence (NIRF) and photoacoustic (PA) dual-modal imaging. LET-3, composed of NIR hemicyanine dye (LET-CyOH) and a phosphate moiety, showed a 23-fold NIRF enhancement at 730 nm and 27-fold PA enhancement at 710 nm upon activation by ALP. More importantly, both in vitro and in vivo diagnostic experiments indicated that LET-3 has a high sensitivity and good selectivity for ALP. These findings provide a promising strategy for in vivo ALP detection using NIRF and PA dual-channel turn-on probes.

pH-Responsive Nanoprobe for In Vivo Photoacoustic Imaging of Gastric Acid.

In vivo real-time monitoring gastric acid is of great importance for diagnosis and treatment of gastrointestinal diseases. Herein, we synthesized a pH-responsive photoacoustic (PA) nanoprobe (denoted as LET-4) based on near-infrared (NIR) dye (IR1061) for in vivo photoacoustic imaging (PAI) of gastric acid in living subjects. In the acidic condition, the protonated LET-4 nanoprobe has a strong absorbance peak at 808 nm, followed by a strong PA signal output at 808 nm. The PA808 signal at pH 3 is 3.45-fold higher than the signal at pH 7. More importantly, the LET-4 nanoprobe could monitor in vivo gastric acid secretion assessment in animal model using PAI. This organic small molecule NIR dye-based probe with simple components, facile preparation, good biocompatibility, and rapid excretion has great potential for gastrointestinal disease diagnosis.

In Vivo Chemoselective Photoacoustic Imaging of Copper(II) in Plant and Animal Subjects.

The detection of Cu2+ in living plants and animals is of great importance for environment monitoring and disease diagnosis. Here, a near-infrared (NIR) turn-on photoacoustic (PA) probe (denoted as LET-2) is developed for Cu2+ detection in living subjects, such as soybean sprouts and mice. The absorbance band of LET-2 shifts from 625 to 715 nm after the interaction with Cu2+ , thus producing strong PA signal output at 715 nm (PA715 ) as an indicator. The PA715 value is increased as a function of the concentration of Cu2+ (0 × 10-6 -20 × 10-6 m), with a calculated limit of detection of 10.8 × 10-9 m. More importantly, both in vitro and in vivo studies in soybean sprouts and mice indicate that the as-prepared LET-2 PA probe is highly sensitive and selective for Cu2+ detection. These findings provide a solution for in vivo detection of metal ions by using chemoselective PA probes.

In Vivo Photoacoustic Detection and Imaging of Peroxynitrite.

Photoacoustic detection is an emerging noninvasive and nonionizing detection technique with the merits of rich contrast, high resolution, and deep tissue penetration, especially for in vivo detection and imaging. Herein, we developed a photoacoustic (PA) molecular imaging probe (denoted as nanonaps) composed of a naphthalocyanine dye and a heptamethine dye as the internal standard with unchanged signals at 860 nm and the sensing component with peroxynitrite (ONOO-) target-decreased signals at 775 nm, respectively. The as-prepared nanonaps displayed high sensitivity and specificity of ONOO- both in vitro and in vivo. The PA860/PA775 ratio was increased as a function of the concentration of ONOO- (0-250 nM). More interestingly, our ratiometric nanonaps could be used for in vivo detection and imaging of ONOO-.

Photoacoustic Probes for Molecular Detection: Recent Advances and Perspectives.

Photoacoustic (PA) imaging (PAI) is a noninvasive and nonionizing biomedical imaging modality that combines the advantages of optical imaging and ultrasound imaging. Based on PAI, photoacoustic detection (PAD) is an emerging approach that is involved with the interaction between PA probes and analytes resulting in the changes of photoacoustic signals for molecular detection with rich contrast, high resolution, and deep tissue penetration. This Review focuses on the recent development of PA probes in PAD. The following contents will be discussed in detail: 1) the construction of PA probes; 2) the applications and mechanisms of PAD to different types of analytes, including microenvironments, small biomolecules, or metal ions; 3) the challenges and perspectives of PA probes in PAD.

Precision Photothermal Therapy at Mild Temperature: NIR-II Imaging-Guided, H2O2-Responsive Stealth Nanobomb.

The therapeutic efficacy of photothermal therapy (PTT) under mild temperatures (<45 °C) is hindered as cancer cells can activate heat shock proteins (HSPs) to mend fever-type cellular damage swiftly. The previous attempt fabricated first-generation nanobombs (nanobomb1G) by self-assembly of polymeric NIR-II AIEgens and carbon monoxide (CO) carrier polymer mPEG(CO) to inhibit the expression of HSPs after intratumor injection. A new generation nanobomb (Stealth NanoBomb (SNB)) is developed by self-assembling small molecular NIR-II AIEgens with CO carrier polymer PLGA(CO) coated by PEG-lipid. This design allows for intravenous administration, enabling the SNB to circulate safely in the bloodstream and selectively target cancer cells. Upon accumulation in tumors, the SNB releases CO to effectively suppress HSP expression, enhancing the therapeutic efficacy of mild-temperature PTT. Compared to the previous generation, the SNB offers a safer, more stable, and more efficient CO gas/drug co-delivery system for cancer treatment. This work represents a significant advancement in PTT, providing a promising strategy for enhanced antitumor therapy with reduced systemic toxicity.

Immunocyte Membrane-Coated Nanoparticles for Cancer Immunotherapy.

Despite the advances in surface bioconjugation of synthetic nanoparticles for targeted drug delivery, simple biological functionalization is still insufficient to replicate complex intercellular interactions naturally. Therefore, these foreign nanoparticles are inevitably exposed to the immune system, which results in phagocytosis by the reticuloendothelial system and thus, loss of their biological significance. Immunocyte membranes play a key role in intercellular interactions, and can protect foreign nanomaterials as a natural barrier. Therefore, biomimetic nanotechnology based on cell membranes has developed rapidly in recent years. This paper summarizes the development of immunocyte membrane-coated nanoparticles in the immunotherapy of tumors. We will introduce several immunocyte membrane-coated nanocarriers and review the challenges to their large-scale preparation and application.

Glucose Oxidase-Instructed Fluorescence Amplification Strategy for Intracellular Glucose Detection.

The accurate detection of glucose at cellular level remains a big challenge. In this study, a signal amplification strategy mediated by silver nanocube (AgNC), glucose oxidase (GOx), and silver ion fluorescence probe (denoted as AgNC-GOx/Ag+-FP) is proposed for amplified intracellular glucose detection. The AgNC is oxidized into Ag+ by H2O2 generated from GOx-catalyzed glucose oxidation reaction, and Ag+ remarkably enhances the red fluorescence of Ag+-FP. Our results show that AgNC-GOx/Ag+-FP is highly sensitive and specific to glucose and H2O2. Afterward, the feasibility of using AgNC-GOx/Ag+-FP to detect intracellular glucose is verified in five different cell lines. In summary, a sensitive and specific fluorescence amplification strategy has been developed for intracellular glucose detection.

Aggregation induced photoacoustic detection of mercury (â ¡) ions using quaternary ammonium group-capped gold nanorods.

Photoacoustic imaging is an emerging detection tool of metal ions. Mercury is a typical heavy metal pollutant that can cause severe water and soil pollution. Therefore, it is particularly meaningful to develop a photoacoustic probe with excellent selectivity and sensitivity for the detection of mercury ions. In this study, gold nanorods modified with (11-mercapto-undecyl)-trimethylammonium (MTA) molecules containing sulfydryl groups were designed and synthesized for the photoacoustic detection of mercury ions (Hg2+). In the present of Hg2+, MTA molecules would be displaced quickly from the surface of gold nanorods due to the high affinity of Hg2+ toward sulfydryl group. Then gold nanorods were aggregated due to the loss of ligand protection on their surface, resulting in the enhancement of photoacoustic signals. In addition, this work showed a good linear relationship between the change of photoacoustic signal at 780 nm and the concentrations of Hg2+ (0-10 µM). More importantly, the devised photoacoustic detection system performs good stability and anti-interference compared to the traditional colorimetric detection system, making it possible to apply to the actual Hg2+-contaminated water samples.