Photoacoustic (PA) technology can transform light energy into acoustic wave, which can be used for either imaging or therapy that depends on the power density of pulsed laser. Here, we report photosensitizer‐free polymeric nanocapsules loaded with nitric oxide (NO) donors, namely NO‐NCPs, formulated from NIR light‐absorbable amphiphilic polymers and a NO‐releasing donor, DETA NONOate. Controlled NO release and nanocapsule dissociation are achieved in acidic lysosomes of cancer cells. More importantly, upon pulsed laser irradiation, the PA cavitation can excite water to generate significant reactive oxygen species (ROS) such as superoxide radical (O2.−), which further spontaneously reacts with the in situ released NO to burst highly cytotoxic peroxynitrite (ONOO−) in cancer cells. The resultant ONOO− generation greatly promotes mitochondrial damage and DNA fragmentation to initiate programmed cancer cell death. Apart from PA imaging, PA cavitation can intrinsically amplify reactive species via photosensitization‐free materials for promising disease theranostics.

In multiple types of tumors, fibrotic collagen is regarded as the 'highway' for cancer cell migration, which is mainly modified by lysyl hydroxylase 2 (PLOD2). The previous findings have demonstrated that the expression of PLOD2 was regulated by multiple factors, including HIF-1α, TGF-β and microRNA-26a/b. Although PLOD2 was confirmed to be related to poor prognosis in lung adenocarcinoma, the regulatory mechanism and function of PLOD2 in human lung adenocarcinoma is poorly understood. On the other hand, upregulation or hyperactivation of epidermal growth factor receptor is considered as a prognostic marker in many cancers, especially in non-small-cell lung cancer (NSCLC). In this study, we found that PLOD2 was elevated in NSCLC specimens and positively links to NSCLC poor prognosis. Gain- and loss-of-function studies and orthotopic implantation metastasis model pinpointed that PLOD2 promotes NSCLC metastasis directly by enhancing migration and indirectly by inducing collagen reorganization. In addition, we revealed that PLOD2 was regulated by PI3K/AKT-FOXA1 axis. The transcription factor FOXA1 directly bound to the PLOD2 promoter, and turned on PLOD2 transcription. In summary, our findings revealed a regulatory mechanism of NSCLC metastasis through EGFR-PI3K/AKT-FOXA1-PLOD2 pathway, and provided PLOD2 as a therapeutic target for NSCLC treatment.

Biofilm can protect bacteria from immune attacks and antibiotic inhibition, and bacterial biofilm hosted in implanted materials and medical devices is a serious threat for modern medical system. Herein, we report biofilm-responsive caged guanidine nanoparticles (CGNs) to deeply penetrate and accumulate in bacterial biofilm, and then efficient photothermal eradication of bacterial biofilm is achieved upon NIR laser irradiation via the proof-of-concept formulation of photothermal agents in CGNs. In physiological conditions and blood circulation, CGNs are negatively charged by masking the positive charge of guanidine via covalent modification with acid-cleavable moieties, exhibiting high biocompatibility and minimal hemolysis. Whereas upon blood circulation and passive accumulation at infected implant sites, CGNs are self-adaptive in acidic biofilm to release the protective caging group and expose native guanidine moieties, which can promote nanoparticle deep biofilm penetration and bacteria adhesion as well as membrane fusion. After that, remarkable photothermal effect with a high photothermal conversion efficiency of ∼40.9% can eradicate implant biofilm upon NIR laser irradiation. It can efficiently treat S. aureus biofilminfected implant catheters in vivo via only one single treatment in a mouse model, exhibiting ∼99.6% bacteria inhibition ratio. Apart from this proof-of-concept work, current guanidine-caged biofilm responsive polymeric nanoparticles are promising general vectors to treat biofilm and resistant pathogens in medicine and daily healthcare.