Impaired diabetic wound healing represents a devastating and rapidly growing clinical problem associated with high morbidity, mortality, and recurrence rates. Engineering therapeutic angiogenesis in the wounded tissue is critical for successful wound healing. However, stimulating functional angiogenesis of the diabetic wound remains a great challenge, due to the oxidative damage and denaturation of bio-macromolecule-based angiogenic agents in the oxidative diabetic wound microenvironment. Here, we present a unique “seed-and-soil” strategy that circumvents the limitation by simultaneously reshaping the oxidative wound microenvironment into a proregenerative one (the “soil”) and providing proangiogenic miRNA cues (the “seed”) using an miRNA-impregnated, redox-modulatory ceria nanozyme-reinforced self-protecting hydrogel (PCN-miR/Col). The PCN-miR/Col not only reshapes the hostile oxidative wound microenvironment, but also ensures the structural integrity of the encapsulated proangiogenic miRNA in the oxidative microenvironment. Diabetic wounds treated with the PCN-miR/Col demonstrate a remarkably accelerated wound closure and enhanced quality of the healed wound as featured by highly ordered alignment of collagen fiber, skin appendage morphogenesis, functional new blood vessel growth, and oxygen saturation.

Simultaneous photothermal therapy (PTT) and photodynamic therapy (PDT) is beneficial for enhanced cancer therapy due to the synergistic effect. Conventional materials developed for synergistic PTT/PDT are generally multicomponent agents that need complicated preparation procedures and be activated by multiple laser sources. The emerging monocomponent diketopyrrolopyrrole (DPP)-based conjugated small molecular agents enable dual PTT/PDT under a single laser irradiation, but suffer from low singlet oxygen quantum yield, which severely restricts the therapeutic efficacy. Herein, we report acceptor-oriented molecular design of a donor–acceptor–donor (D–A–D) conjugated small molecule (IID-ThTPA)-based phototheranostic agent, with isoindigo (IID) as selective acceptor and triphenylamine (TPA) as donor. The strong D–A strength and narrow singlet–triplet energy gap endow IID-ThTPA nanoparticles (IID-ThTPA NPs) high mass extinction coefficient (18.2 L g⁻¹ cm⁻¹), competitive photothermal conversion efficiency (35.4%), and a dramatically enhanced singlet oxygen quantum yield (84.0%) comparing with previously reported monocomponent PTT/PDT agents. Such a high PTT/PDT performance of IID-ThTPA NPs achieved superior tumor cooperative eradicating capability in vitro and in vivo.

Chemically defined conjugated small molecules (CSMs) and their nanoparticles (CSMNs) have been widely used in phototheranostics. However, CSMNs have rarely been studied for second near-infrared (NIR-II) deep-tissue photothermal therapy (PTT) due to the lack of NIR-II-absorbing CSMNs. Herein, through a molecular engineering strategy of “increasing the number of thiophene bridges”, three donor–acceptor–donor (D–A–D) CSMs, namely CSM0-2 in which the number represents the number of thiophene bridges, have been synthesized. The optical bandgap decreases with the increase of the number of thiophene bridges. Among them, CSM2 has strong absorption in both the first near-infrared (NIR-I) and NIR-II regions. CSMN2 exhibits high photothermal conversion efficiency (PTCE = 31.6%) in NIR-II and excellent biocompatibility. By using CSMN2, photoacoustic imaging (PAI)-guided in vivo tumor NIR-II PTT is achieved under low laser power density (0.5 W cm⁻²). The molecular engineering strategy reported here can potentially be applied to other D–A systems for the development of new materials in phototheranostics.

Near‐infrared (NIR) absorbing materials hold great potential in biomedical applications, such as fluorescence imaging (FLI), photoacoustic imaging (PAI), photodynamic therapy (PDT), and photothermal therapy (PTT). Generally, these materials can be classified into two main categories based on their absorbing wavelengths: the first NIR (NIR‐I) (~650–950 nm) absorbing materials and the second NIR (NIR‐II) (~1000–1700 nm) absorbing materials. Due to the reduced absorption and scattering of NIR‐II light in tissue compared to NIR‐I light, NIR‐II absorbing materials enable imaging and therapy with improved contrast and deepened penetration, which is in favor of practical applications. Various inorganic materials have been developed for NIR‐II phototheranostics in recent years. However, the non‐biodegradability and potential toxicity of these materials hinder their further clinical translation. Biocompatible organic materials with potential biodegradability as well as tailored optical property are thus more desired. In this review, we summarize the recent advances of NIR‐II absorbing organic nanoagents (ONAs) based on small molecules (SMs) and conjugated polymers (CPs) for PAI and PTT and show our perspectives on future challenges and development of these materials.