The combination of reactive oxygen species (ROS)-involved photodynamic therapy (PDT) and chemodynamic therapy (CDT) holds great promise for enhancing ROS-mediated cancer treatment. Herein, we reported an in situ polymerized hollow mesoporous organosilica nanoparticle (HMON) biocatalysis nanoreactor to integrate the synergistic effect of PDT/CDT for enhancing ROSmediated pancreatic ductal adenocarcinoma treatment. HPPH photosensitizer was hybridized within the framework of HMON via an "in situ framework growth" approach. Then, the hollow cavity of HMONs was exploited as a nanoreactor for "in situ polymerization" to synthesize the polymer containing thiol groups, thereby enabling the immobilization of ultrasmall gold nanoparticles, which behave like glucose oxidase-like nanozyme, converting glucose into H 2 O 2 to provide self-supplied H 2 O 2 for CDT. Meanwhile, Cu 2+ -tannic acid complexes were further deposited on the surface of HMONs (HMON-Au@Cu-TA) to initiate Fenton-like reaction to covert the self-supplied H 2 O 2 into •OH, a highly toxic ROS. Finally, collagenase (Col), which can degrade the collagen I fiber in the extracellular matrix (ECM), was loaded into HMON-Au@Cu-TA to enhance the penetration of HMONs and O 2 infiltration for enhanced PDT. This study provides a good paradigm for enhancing ROS-mediated anti-tumor efficacy. Meanwhile, this research offers a new method to broaden the application of silica based nanotheranostics.

Acute venous thrombosis is prevalent and potentially fatal. Accurate diagnosis of early thrombus is needed for patients in timely clinical intervention to prevent life-threatening conditions. Photoacoustic imaging (PAI) with excellent spatial resolution and high optical contrast shows more promise for this purpose. However, its application is dramatically limited by its signal-off effect on thrombus because of the ischemia in thrombus which lacks the endogenous photoacoustic (PA) signal of hemoglobin. To address this dilemma, we herein report the feasibility of using organic semiconducting nanoparticles (NPs) for contrast-enhanced PAI of thrombus in living mice. An organic semiconducting NP, self-assembled by amphiphilic perylene-3,4,9,10-tetracarboxylic diimide (PDI) molecules, is chemically modified with cyclic Arg-Gly-Asp (cRGD) peptides as a PA contrast agent (cRGD-PDI NPs) for selectively lightening early thrombus. cRGD-PDI NPs presents high PA intensity, good stability in light and serum, and sufficient blood-circulating half-life. In living mice, PA intensity of early thrombus significantly increases after tail vein injection of cRGD-PDI NPs, which is 4-fold greater than that of the control, blocking, and old thrombus groups. Pathological and immunohistochemical findings show that glycoprotein IIb/IIIa abundant in early thrombus is a good biomarker targeted by cRGD-PDI NPs for distinguishing early thrombus from old thrombus by PAI. Such a lightening PAI effect by cRGD-PDI NPs successfully provides accurate information including the profile, size and conformation, and spatial distribution of early thrombus, which may timely monitor the obstructive degree of thrombus in blood vessels and the thrombolysis effect.

Cartilage degeneration is the hallmark of osteoarthritis (OA) and its early diagnosis is essential for effective cartilage repair. However, until now, there was still a lack of imaging modalities that can accurately detect and evaluate cartilage degeneration in its early stage. Herein, we introduce endogenous melanin nanoparticles (MNPs) encapsulated by poly-l-lysine (PLL) as positively charged contrast agents for the accurate photoacoustic (PA) imaging of cartilage degeneration through its strong electrostatic interaction with anionic glycosaminoglycans (GAGs) in the cartilage. PLL-MNPs presented high PA intensity, photostability and biocompatibility. In vitro PAI studies showed that PLL-MNPs with a zeta potential of +32.5 ± 9.3 mV had more cartilage uptake and longer retention time than anionic MNPs, and generated a positive relationship with the GAG content in the cartilage. After administration via intra-articular injection in living mouse models, PLL-MNPs exhibited about a two-fold stronger PA signal in a normal joint (with high GAG content) than an OA joint (with low GAG content). Furthermore, the obtained PAI results provided accurate information of the GAG content distribution in the OA knee joint. Consequently, by detecting and analyzing the changes of the GAG content in OA cartilage using PAI, we can clearly distinguish early OA from late OA and monitor the therapeutic efficacy in OA after drug treatment. All PAI results were examined histologically.

No abstract