Vacancy Engineering to Regulate Photocatalytic Activity of Polymer Photosensitizers for Amplifying Photodynamic Therapy against Hypoxic Tumors.

Polymer photosensitizers (PPSs) with the distinctive properties of good light-harvesting capability, high photostability, and excellent tumor retention effects have aroused great research interest in photodynamic therapy (PDT). However, their potential translation into clinic was often constrained by the hypoxic nature of tumor microenvironment, the aggregation-caused reduced production of reactive oxygen species (ROS), and the tedious procedure of manufacture. As a powerful and versatile strategy, vacancy engineering possesses the unique capability to effectively improve the photogenerated electron efficiency of nanomaterials for high-performance O2 and ROS production. Herein, by introducing vacancy engineering into the design of PPSs for PDT for the first time, we synthesized a novel PPS of Au-decorated polythionine (PTh) nanoconstructs (PTh@Au NCs) with the unique integrated features of distinguished O2 self-evolving function and highly efficient ROS generation for achieving the greatly enhanced PDT efficacy toward hypoxic tumor both in vitro and in vivo. The incorporation of Au into PTh leads to the special PTh-Au heterostructure-induced sulfur vacancies in PTh@Au NCs, which results in an efficient electron-hole separation performance and also plays a key role in a long lifetime of free electrons and holes. Accordingly, an ∼2- to 3-fold ROS generation and an ∼1.5-fold increase of O2 self-supply than the pure PTh nanoparticles (NPs) were obtained even under hypoxic conditions upon exposure to 650 nm light. By combining such superior ROS generation and O2 self-supply performances with the outstanding cellular internalization and tumor accumulation capacities, an advanced antitumor effect with the achievement of almost complete hypoxic tumor elimination in vivo or 88% cell destruction in vitro was acquired by the PTh@Au NCs. In addition, the distinctive facile one-step redox strategy for PTh@Au NCs synthesis compared to the reported PPSs for PDT also makes it beneficial for potential practical application. The first introduction of vacancy engineering concept into PPSs in the field of PDT proposed in this work offers a new strategy for the development and design highly efficient PPSs for PDT applications.

Oxygen vacancy-enhanced photothermal performance and reactive oxygen species generation for synergistic tumour therapy.

Vacancy engineering is a robust strategy to tune nanomaterials' electronic structures for physicochemical properties regulation. Here, we report and realize the first oxygen vacancy-enhanced photothermal and oxidation dual-induced synergistic tumour therapy using oxygen vacancies enriched MnO2@Au nanoconstructs as the therapeutic agent with a high photothermal effect, enhanced highly-toxic superoxide radical generation, good biocompatibility and tumour microenvironment regulation capacity. Our work opens up a new route for cancer nanotheranostics by regulating the electronic structure of nanomaterials resulting in enhanced efficacy.

Metal-Organic Framework-Integrated Enzymes as Bioreactor for Enhanced Therapy against Solid Tumor via a Cascade Catalytic Reaction.

Emerging natural-enzyme-based nanocatalytic tumor therapy depending on the high catalytic performance of natural enzymes has inspired great research interest in clinical applications. Nevertheless, the natural-enzyme-based catalytic therapy efficiency is seriously hampered by the low operational stability, poor delivery efficiency, and the short lifetime of enzymes. Herein, a bioreactor based on zeolitic imidazolate framework-8 (ZIF-8) was fabricated through one-pot embedding horseradish peroxidase (HRP) and glucose oxidase (Gox) strategy (ZIF-8@Gox/HRP) for synergistic cancer therapy. Notably, the obtained ZIF-8@Gox/HRP can efficiently consume endogenous glucose to generate gluconic acid and H2O2 for starving tumors, and subsequently, H2O2 was decomposed by encapsulated HRP to release high-toxic •OH radicals, inducing cancer cell apoptosis for oxidation therapy. Importantly, in vivo results showed that ZIF-8@Gox/HRP had an impressive tumor-suppression rate based on cascade catalytic reaction. Therefore, this work paves a new avenue to design smart enzyme-based platforms for safe and efficient cancer therapy.