Ambient Oxygen-Doped Conjugated Polymer for pH-Activatable Aggregation-Enhanced Photoacoustic Imaging in the Second Near-Infrared Window.

Photoacoustic (PA) probes absorbing in the second near-infrared (NIR-II: 1000-1700 nm) window hold great promise for deep-tissue diagnosis and treatment. Currently, NIR-II PA probes typically involve complex synthesis and surfactant adjuvant for processing and delivery. Furthermore, these NIR-II PA probes are "always-on," leading to inadequate signal-to-background ratio and low specificity. To address these challenges, this study reports a pH-activatable and aggregation-enhanced NIR-II PA probe. Without using any toxic or exotic oxidants, the selected polymer (PPE) is readily doped by oxygen in an ambient environment and simultaneously red-shifts its absorption profile from visible to NIR-II region. By virtue of the carboxyl groups on the side chains, oxygen-doped PPE is readily water-soluble at a physiological pH but tends to aggregate in an acidic environment. The pH-induced aggregation results in a significant PA enhancement and thus allows specific PA imaging of acidic tumor microenvironment in vivo. Our study provides a facile and surfactant-free strategy for achieving water-soluble and pH-responsive NIR-II PA probes, which could be applied for diagnoses of cancer and other diseases associated with changes in pH. It paves the way for the development of new activatable NIR-II imaging probes and also could facilitate the investigation of biological and pathological processes in deep tissue.

Functionalized NIR-II Semiconducting Polymer Nanoparticles for Single-cell to Whole-Organ Imaging of PSMA-Positive Prostate Cancer.

Development of molecular probes holds great promise for early diagnosis of aggressive prostate cancer. Here, 2-[3-(1,3-dicarboxypropyl) ureido] pentanedioic acid (DUPA)-conjugated ligand and bis-isoindigo-based polymer (BTII) are synthesized to formulate semiconducting polymer nanoparticles (BTII-DUPA SPN) as a prostate-specific membrane antigen (PSMA)-targeted probe for prostate cancer imaging in the NIR-II window. Insights into the interaction of the imaging probes with the biological targets from single cell to whole organ are obtained by transient absorption (TA) microscopy and photoacoustic (PA) tomography. At single-cell level, TA microscopy reveals the targeting efficiency, kinetics, and specificity of BTII-DUPA SPN to PSMA-positive prostate cancer. At organ level, PA tomographic imaging of BTII-DUPA SPN in the NIR-II window demonstrates superior imaging depth and contrast. By intravenous administration, BTII-DUPA SPN demonstrates selective accumulation and retention in the PSMA-positive tumor, allowing noninvasive PA detection of PSMA overexpressing prostate tumors in vivo. The distribution of nanoparticles inside the tumor tissue is further analyzed through TA microscopy. These results collectively demonstrate BTII-DUPA SPN as a promising probe for prostate cancer diagnosis by PA tomography.

Enzyme-Engineered Conjugated Polymer Nanoplatform for Activatable Companion Diagnostics and Multistage Augmented Synergistic Therapy.

Companion diagnostics (CDx) provides critical information for precision medicine. However, current CDx is mostly limited to in vitro tests, which cannot accurately evaluate the disease progression and treatment response in real time. To overcome this challenge, herein a glucose oxidase (GOx)-engineered conjugated polymer (polyaniline, PANI) nanoplatform (denoted as PANITG) is reported for activatable imaging-based CDx and multistage augmented photothermal/starvation synergistic therapy. PANITG comprises a pH-activatable conjugated polymer as a photothermal convertor and photoacoustic (PA) emitter, a GOx as a cancer starvation inducer as well as a H2 O2 and acid producer, and a H2 O2 -cleavable linker as a "switch" for GOx activity. The in vivo PA imaging and photothermal therapy abilities are activated by acidic tumor microenvironment and self-augmented by the reaction between GOx and glucose. Meanwhile, the photothermal effect will enhance the GOx activity in turn. Such multistage augmentation of the therapeutic effects will facilitate effective cancer management. In addition, the in vivo PA imaging with PANITG reveals the tumor pH level which is correlated to the efficiency of the photothermal therapy and to the catalytic activity of GOx at each stage, enabling real-time activatable CDx.

Weaving Enzymes with Polymeric Shells for Biomedical Applications.

Enzyme therapeutics have received increasing attention due to their high biological specificity, outstanding catalytic efficiency, and impressive therapeutic outcomes. Protecting and delivering enzymes into target cells while retaining enzyme catalytic efficiency is a big challenge. Wrapping of enzymes with rational designed polymer shells, rather than trapping them into large nanoparticles such as liposomes, have been widely explored because they can protect the folded state of the enzyme and make post-functionalization easier. In this review, the methods for wrapping up enzymes with protective polymer shells are mainly focused on. It is aimed to provide a toolbox for the rational design of polymeric enzymes by introducing methods for the preparation of polymeric enzymes including physical adsorption and chemical conjugation with specific examples of these conjugates/hybrid applications. Finally, a conclusion is drawn and key points are emphasized.