Magnetic-Photoacoustic Dual-Mode Probe for the Visualization of H2S in Colorectal Cancer.

Techniques for the qualitative and quantitative detection of H2S in vivo have attracted considerable attention due to the key role of H2S in various physiological and pathological processes. However, in vivo detection strategies for H2S are mainly based on fluorescence imaging, which is limited by its poor tissue penetration. Moreover, the limitations of single-mode probes are amplified in complex physiological environments. Herein, a core-shell Fe3O4@Cu2O nanoparticle was constructed as a magnetic-photoacoustic dual-mode probe for H2S detection in vitro and in vivo based on the in situ response of Cu2O to endogenous H2S in colon tumors. This probe is expected to greatly improve the accuracy of H2S detection in vivo because it employs two detection methods with complementary advantages. The new probe was experimentally applied to the in vivo and in vitro visualization of H2S in mice with colorectal cancer, validating the in situ reaction-activated dual-detection method. This work establishes a simple and efficient dual-mode imaging method based on a novel trigger mechanism. The findings provide a new strategy for colon cancer detection based on the in situ reactions at tumor sites.

A smart theranostic platform for photoacoustic and magnetic resonance dual-imaging-guided photothermal-enhanced chemodynamic therapy.

The use of smart theranostic agents in multimodal imaging and treatment is a promising strategy to overcome the limitations of single mode diagnosis and treatment, and can greatly improve the diagnosis and effects of treatment. In this study, a gold@manganese dioxide (Au@MnO2) core-shell nanostructure was designed as a glutathione (GSH)-triggered smart theranostic agent for photoacoustic and magnetic resonance (MR) dual-imaging-guided photothermal-enhanced chemodynamic therapy. Both in vitro and in vivo experiments demonstrated not only that the photoacoustic and MR imaging function of Au@MnO2 could be activated by a high endogenous GSH concentration, but also that after being triggered by the endogenous GSH, Au@MnO2 had an excellent synergistic treatment effect in photothermal-enhanced chemodynamic therapy under the guidance of photoacoustic and MR imaging. This study demonstrated that the use of GSH-triggered Au@MnO2 in photoacoustic and MR dual-imaging-guided photothermal-enhanced chemodynamic therapy is a smart theranostic nanoplatform for the accurate diagnosis and efficient treatment of cancer.

pH and Glutathione Synergistically Triggered Release and Self-Assembly of Au Nanospheres for Tumor Theranostics.

Theranostic agents based on near-infrared absorption which integrate both imaging and therapeutic functions have attracted considerable attention. However, because of the interference signal, indiscriminate treatment usually causes side effects on normal tissues during tumor treatment. To address this limitation, we propose a new synergistically triggered mechanism, release and self-assembly of Au nanospheres, for tumor theranostics based on the synergistic effect of H+ and glutathione on the tumor microenvironment. In vitro experiments reveal that Au nanospheres release from Au@ZIF-8 at a high concentration of H+ or glutathione. Importantly, Au aggregation only appears in the synergistic effect of glutathione and lower pH and exhibits strong coupling plasmonic resonance absorption in the near-infrared region and can be used as the theranostics agent. This statement was further verified by biological transmission electron microscopy and in vivo imaging. Au@ZIF-8 is stable and produces no photoacoustic signal in normal tissue; in contrast, in the presence of overexpressed glutathione and H+, Au nanospheres release from Au@ZIF-8, assemble to aggregates, and exhibit a strong signal at the tumor site for imaging and efficient photothermal therapy. This work provides a new strategy for designing theranostic agents with sequentially responsive steps to avoid interference diagnosis signals from normal tissues and reduce damage to normal tissue during treatment.

Mn-Porphyrin-Based Metal-Organic Framework with High Longitudinal Relaxivity for Magnetic Resonance Imaging Guidance and Oxygen Self-Supplementing Photodynamic Therapy.

A nanoplatform for magnetic resonance imaging guidance and oxygen self-supplementing photodynamic therapy (PDT) was constructed on the basis of a porous metal-organic framework (PCN-222(Mn)), which was built by simple Mn-porphyrin ligands and biocompatible Zr4+ ions. Because of the good dispersibility of Mn3+ in the open framework and the high water affinity of the channel, PCN-222(Mn) exhibits a high longitudinal relaxivity of ∼35.3 mM-1 s-1 (1.0 T). In addition, it shows good catalytic activity for the conversion of endogenous hydrogen peroxide into oxygen, thereby improving tumor hypoxia during photodynamic therapy. The intravenous injection of PCN-222(Mn) into tumor-bearing mice mode provided good T1-weighted contrast of the tumor site and effectively inhibited tumor growth upon a single-laser irradiation. The findings provide insights for the development of multifunctional theranostic nanoplatforms based on simple components.

Surface Plasmon Resonance-Enhanced Photoacoustic Imaging and Photothermal Therapy of Endogenous H2 S-Triggered Au@Cu2 O.

Smart theranostics agents triggered by endogenous H2 S with combined activated photoacoustic imaging and photothermal therapy can improve the diagnosis and treatment of colon cancer. However, the low theranostic performance of the current smart theranostics agents after the triggering step has limited their further application. In this work, the theranostic performance of endogenous H2 S-triggered Au@Cu2 O for the diagnosis and treatment of colon cancer, which is generated from the localized surface plasmon resonance coupling effect between a noble metal (Au) and a semiconductor (Cu2 O), is investigated. Compared with Cu2 O, the prepared H2 S-triggered Au@Cu2 O shows a significantly stronger absorption at the near-infrared region, such as a ≈2.1 times change at 808 nm, giving a photothermal conversion efficiency increase of ≈1.2 times. More importantly, Au@Cu2 O still exhibits good photoacoustic imaging contrast and photothermal properties for treatment of colon cancer in vivo even at very low injection doses. This work not only investigates an endogenous H2 S-triggered Au@Cu2 O theranostic agent with enhanced theranostic performance for colon cancer but also provides a novel strategy for designing high-performance theranostic agents.

Tumor pH-Responsive Albumin/Polyaniline Assemblies for Amplified Photoacoustic Imaging and Augmented Photothermal Therapy.

Tumor-microenvironment-responsive theranostics have great potential for precision diagnosis and effective treatment of cancer. Polyaniline (PANI) is the first reported pH-responsive organic photothermal agent and is widely used as a theranostic agent. However, tumor pH-responsive PANI-based theranostic agents are not explored, mainly because the conversion from the emeraldine base (EB) to emeraldine salt (ES) state of PANI requires pH < 4, which is lower than tumor acidic microenvironment. Herein, a tumor pH-responsive PANI-based theranostic agent is designed and prepared for amplified photoacoustic imaging guided augmented photothermal therapy (PTT), through intermolecular acid-base reactions between carboxyl groups of bovine serum albumin (BSA) and imine moieties of PANI. The albumin/PANI assemblies (BSA-PANI) can convert from the EB to ES state at pH < 7, accompanied by the absorbance redshift from visible to near-infrared region. Both in vitro and in vivo results demonstrate that tumor acidic microenvironment can trigger both the photoacoustic imaging (PAI) signal amplification and the PTT efficacy enhancement of BSA-PANI assemblies. This work not only highlights that BSA-PANI assemblies overcome the limitation of low-pH protonation, but also provides a facile assembly strategy for a tumor pH-responsive PANI-based nanoplatform for cancer theranostics.

Macrophages-Mediated Delivery of Small Gold Nanorods for Tumor Hypoxia Photoacoustic Imaging and Enhanced Photothermal Therapy.

Macrophage-mediated delivery of drugs or nanoparticles has great potential in cancer treatment because it can avoid interception by the immune system and cross the blood-vessel barriers to reach the hypoxic regions of tumors. However, macrophage-based delivery system still faces some great challenges such as low theranostics agent loading capacity and hypoxic regions tendency in vivo. Herein, small gold nanorods (AuNRs) were used as the model theranostics agent to design a macrophage-mediated delivery system with high loading quantity for tumor hypoxia photoacoustic (PA) imaging and enhanced photothermal therapy (PTT). AuNRs modified with various thiolated poly(ethylene glycol)s (HS-PEG) via ligand exchange were investigated for toxicity and cell uptake by macrophages. The tumor hypoxic regions tendency of macrophage-loaded Anionic-AuNRs (Anionic-AuNRs@RAW) were verified by in vivo PA imaging and tumor sections. In vivo systemic PTT demonstrated enhanced tumor inhibition of anionic-AuNRs@RAW. This macrophage-mediated delivery system with high loading capacity could be used to enhance the effectiveness of cancer treatment.

Ultrasmall WO3- x@γ-poly-l-glutamic Acid Nanoparticles as a Photoacoustic Imaging and Effective Photothermal-Enhanced Chemodynamic Therapy Agent for Cancer.

Synergistic treatment strategies for cancer have attracted increasing attention owing to their enhanced therapeutic effects compared with monotherapy. Chemodynamic therapy (CDT) is an emerging and thriving in situ treatment for cancer owing to its high regioselectivity and activation only by endogenous substances. However, the therapeutic effects of CDT are hindered by low reaction speeds. Here, ultrasmall WO3- x@γ-poly-l-glutamic acid (WO3- x@γ-PGA) nanoparticles (NPs) with good photoacoustic and photothermal properties were prepared, and their chemodynamic performance based on a Fenton-like reaction was explored due to its good catalytic effect. The synergistic treatment effect was also investigated by photothermal-enhanced CDT based on single WO3- x@γ-PGA NPs using a penetrating near-infrared-II laser both in vitro and in vivo. This work provides an effective treatment for cancer and further develops the CDT.

BSA-assisted synthesis of ultrasmall gallic acid-Fe(III) coordination polymer nanoparticles for cancer theranostics.

Protein-related nanotheranostic agents hold great promise as tools to serve many clinical applications. Proteins such as BSA are used to regulate the synthesis of nondegradable inorganic nanoparticles (NPs). To fully employ the potential of such proteins, a new type of biosafe nanotheranostic agent must be designed to optimize BSA as a biomineralization agent. Here, a straightforward BSA-assisted biomineralization method was developed to prepare gallic acid (GA)-Fe(III) coordination polymer NPs. BSA-coated GA-Fe (GA-Fe@BSA) NPs were ultrasmall (3.5 nm) and showed good biocompatibility, a lower r2:r1 ratio (1.06), and strong absorption in the visible near-infrared region. T1-weighted magnetic resonance imaging of tumor-bearing mice before and after intratumoral injection with GA-Fe@BSA NPs definitively demonstrated positive change. In a subsequent in vivo study, antitumor activity was precipitated by intratumoral injection of GA-Fe@BSA NPs combined with laser treatment, suggesting excellent outcomes with this treatment method. These results describe a successful protocol in which BSA regulated the synthesis of benign organic polymer NPs. GA-Fe@BSA NPs have the potential to be ideal agents to be used in clinical theranostic nanoplatforms.