Search

Temporal control of delivery and release of drugs in tumors are important in improving therapeutic outcomes to patients. Here, we report a sequential stimuli-triggered in situ self-assembly and disassembly strategy to direct delivery and release of theranostic drugs in vivo. Using cisplatin as a model anticancer drug, we design a stimuli-responsive small-molecule cisplatin prodrug (P-CyPt), which undergoes extracellular alkaline phosphatase-triggered in situ self-assembly and succeeding intracellular glutathione-triggered disassembly process, allowing to enhance accumulation and elicit burst release of cisplatin in tumor cells. Compared with cisplatin, P-CyPt greatly improves antitumor efficacy while mitigates off-target toxicity in mice with subcutaneous HeLa tumors and orthotopic HepG2 liver tumors after systemic administration. Moreover, P-CyPt also produces activated near-infrared fluorescence (at 710 nm) and dual photoacoustic imaging signals (at 700 and 750 nm), permitting high sensitivity and spatial-resolution delineation of tumor foci and real-time monitoring of drug delivery and release in vivo. This strategy leverages the advantages offered by in situ self-assembly with those of intracellular disassembly, which may act as a general platform for the design of prodrugs capable of improving drug delivery for cancer theranostics. Manipulating molecular self-assembly and disassembly in vivo may permit temporal control of drug delivery and release. Here, the authors report a fluorogenic cisplatin prodrug for cancer theranostics by leveraging stimuli-triggered in situ self-assembly and intracellular disassembly processes. [ABSTRACT FROM AUTHOR]

Reversible imaging probes that allow for the dynamic visualization of the redox cycle between hydroxyl radical (⋅OH) and hydrogen sulfide (H2S) are vital to probe the redox imbalance‐involved pathological process in vivo. Herein, we report a reversible ratiometric photoacoustic (PA) imaging nanoprobe (1‐PAIN) for the real‐time imaging of ⋅OH/H2S redox cycle in vivo. 1‐PAIN displays a low PA ratio between 690 and 825 nm (PA690/PA825), which significantly increases by ≈5‐fold upon oxidation by ⋅OH, and is switched back to the initially low PA690/PA825 value upon reduction by H2S. 1‐PAIN could dynamically report on the hepatic ⋅OH production in mice during the lipopolysaccharide (LPS)‐induced liver inflammation process, and visualize hepatic H2S generation during the N‐acetyl cysteine (NAC)‐induced anti‐inflammation process. 1‐PAIN can act as a useful tool to probe the redox state in living biology, beneficial for the study of redox imbalance‐related diseases. [ABSTRACT FROM AUTHOR]

Enzyme‐triggered macrocyclization and in situ self‐assembly of small molecules into nanoparticles has shown promise to design activatable probes for molecular imaging. However, controlling macrocyclization and self‐assembly to concurrently augment positron emission tomography (PET) and photoacoustic (PA) signals for bimodality imaging is challenging. Herein, we report the engineering of a triazole‐IR780 fluorophore as a versatile macrocyclization scaffold for controlling in situ self‐assembly and design a caspase‐3‐activatable PA/PET bimodal probe ([18F]‐IR780‐1) for in vivo imaging of tumor apoptosis. By leveraging the high‐sensitivity whole‐body imaging signals offered by PET with the high‐resolution imaging signals offered by PA, [18F]‐IR780‐1 can provide a promising tool for the early evaluation of antitumor efficacy, helpful for optimizing the therapeutic protocol for patients. This scaffold may be adopted to design other activatable bimodal probes for in vivo imaging. [ABSTRACT FROM AUTHOR]

Photoacoustic (PA) imaging shows promise in the sensitive detection of caspase‐3 activated in early tumor apoptosis in response to chemotherapy; smart PA probes are thus in high demand. Herein, we report the first smart PA probe (1‐RGD) responsive to caspase‐3, enabling real‐time and high‐resolution imaging of tumor apoptosis. 1‐RGD is designed to leverage the synergetic effect of active delivery and caspase‐3 activation. It is selectively recognized by active caspase‐3 to trigger peptide substrate cleavage and biocompatible macrocyclization‐mediated self‐assembly, leading to an amplified PA imaging signal and prolonged retention in apoptotic tumor cells. Strong, high‐resolution PA images are obtained in chemotherapy‐induced apoptotic tumors in living mice after intravenous administration with 1‐RGD, facilitating sensitive reporting of caspase‐3 activity and distribution within tumor tissues. Good vibrations: The caspase‐3‐mediated biocompatible macrocyclization and self‐assembly of a photoacoustic (PA) probe, 1‐RGD, into indocyanine green (ICG)‐containing nanoparticles is reported. The probe allows the enhancement of PA imaging signals for the real‐time detection of tumor apoptosis in living mice with high sensitivity and spatial resolution. [ABSTRACT FROM AUTHOR]

Multimodal imaging probes have shown promise in both biomedical research and clinical diagnosis. However, the development of molecular probes capable of being switched on multimodality imaging signals in response to a biomarker of interest remains challenging. In this paper, we report a caspase-3-activatable small-molecule bimodal probe (Gd-IR780) for photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) of tumor apoptosis via caspase-3-triggered intramolecular macrocyclization and in situ self-assembly process. Upon interaction with caspase-3, Gd-IR780 can be efficiently converted into a macrocyclic product, Gd-IR780-MC , which subsequently self-assembles into near-infrared absorptive and paramagnetic nanoparticles (Gd-IR780-NPs), allowing to concurrently switch on PAI (∼4.3-fold at 855 nm) and MRI (r 1 relaxivity increases from 7.98 ± 0.03 mM−1 s−1 to 19.66 ± 0.7 mM−1 s−1 at 0.5 T) bimodal signals in caspase buffer. Noninvasive in vivo imaging results show that Gd-IR780 can enter apoptotic U87MG tumor tissues after systemic administration, and produce markedly enhanced PAI and MRI signals for high sensitivity and spatial-resolution visualization of caspase-3 activity in the doxorubicin-treated apoptotic U87MG tumor tissues. Gd-IR780 holds a good potential to report tumor apoptosis via combined PAI and MRI, which is beneficial for the early evaluation of antitumor efficacy in vivo. • First activatable photoacoustic (PA) and magnetic resonance (MR) bimodal probe for in vivo imaging of tumor apoptosis. • Caspase-3-mediated in situ self-assembly strategy was used to activate PA and MR bimodal signals simultaneously. • Enhanced PA and MR signals in DOX-treated tumors are achieved, beneficialfor the early monitoring of chemotherapy efficacy. [ABSTRACT FROM AUTHOR]