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Theranostic systems combining fluorescence imaging in the second near-infrared window (NIR-II, 1000–1700 nm) and photothermal therapy (PTT) under safe laser fluence have great potential in preclinical research and clinical practice, but the development of such systems with sufficient effective NIR-II brightness and excellent photothermal properties is still challenging. Here we report a theranostic system based on semiconducting polymer nanoparticles (L1057 NPs) for NIR-II fluorescence imaging and PTT under a 980 nm laser irradiation, with low (25 mW/cm2) and high (720 mW/cm2) laser fluence, respectively. Taking into consideration multiple parameters including the extinction coefficient, the quantum yield, and the portion of emission in the NIR-II region, L1057 NPs have much higher effective NIR-II brightness than most reported organic NIR-II fluorophores. The high brightness, together with good stability and excellent biocompatibility, allows for real-time visualization of the whole body and brain vessels and the detection of cerebral ischemic stroke and tumors with high clarity. The excellent photothermal properties and high maximal permissible exposure limit at 980 nm allow L1057 NPs for PTT of tumors under safe laser fluence. This study demonstrates that L1057 NPs behave as an excellent theranostic system for NIR-II imaging and PTT under safe laser fluence and have great potential for a wide range of biomedical applications.

An exciting new direction in responsive liposome research is endogenous triggering of liposomal payload release by overexpressed enzyme activity in affected tissues and offers the unique possibility of active and site-specific release. Bringing to fruition the fully expected capabilities of this new class of triggered liposomal delivery system requires a collection of liposome systems that respond to different upregulated enzymes; however, a relatively small number currently exist. Here we show that stable, ~100 nm diameter liposomes can be made from previously unreported quinone-dioleoyl phosphatidylethanolamine (Q-DOPE) lipids, and complete payload release (quenched fluorescent dye) from Q-DOPE liposomes occurs upon their redox activation when the quinone headgroup possesses specific substituents. The key component of the triggerable, contents-releasing Q-DOPE liposomes is a “trimethyl-locked” quinone redox switch attached to the N-terminus of DOPE lipids that undergoes a cleavage event upon two-electron reduction. Payload release by aggregation and leakage of “uncapped” Q-DOPE liposomes is supported by results from liposomes wherein deliberate alteration of the “trimethyl-locked” switch completely deactivates the redox-destructible phenomena (liposome opening). We expect that Q-DOPE liposomes and their variants will be important in treatment of diseases with associated tissues that overexpress quinone reductases, such as cancers and inflammatory diseases, because the quinone redox switch is a known substrate for this group of reductases.

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How to improve effective accumulation and intratumoral distribution of plasmonic gold nanoparticles has become a great challenge for photothermal therapy of tumors. Herein, we reported a nanoplatform with photothermal therapeutic effects by fabricating Au nanorods@SiO2@CXCR4 nanoparticles and loading the prepared nanoparticles into the human induced pluripotent stem cells(AuNRs-iPS). In virtue of the prominent optical properties of Au nanorods@SiO2@CXCR4 and remarkable tumor target migration ability of iPS cells, the Au nanorods delivery mediated by iPS cells via the nanoplatform AuNRs-iPS was found to have a prolonged retention time and spatially even distribution in MGC803 tumor-bearing nude mice observed by photoacoustic tomography and two-photon luminescence. On the basis of these improvements, the nanoplatform displayed a robust migration capacity to target the tumor site and to improve photothermal therapeutic efficacy on inhibiting the growth of tumors in xenograft mice under a low laser power density. The combination of gold nanorods with human iPS cells as a theranostic platform paves an alternative road for cancer theranostics and holds great promise for clinical translation in the near future.

Gastric cancer is the second leading cause of cancer-related death worldwide. RNA nanotechnology has recently emerged as an important field due to recent finding of its high thermodynamic stability, favorable and distinctive in vivo attributes. Here we reported the use of the thermostable three-way junction (3WJ) of bacteriophage phi29 motor pRNA to escort folic acid, a fluorescent image marker and BRCAA1 siRNA for targeting, imaging, delivery, gene silencing and regression of gastric cancer in animal models. In vitro assay revealed that the RNA nanoparticles specifically bind to gastric cancer cells, and knock-down the BRCAA1 gene. Apoptosis of gastric cancer cells was observed. Animal trials confirmed that these RNA nanoparticles could be used to image gastric cancer in vivo, while showing little accumulation in crucial organs and tissues. The volume of gastric tumors noticeably decreased during the course of treatment. No damage to important organs by RNA nanoparticles was detectible. All the results indicated that this novel RNA nanotechnology can overcome conventional cancer therapeutic limitations and opens new opportunities for specific delivery of therapeutics to stomach cancer without damaging normal cells and tissues, reduce the toxicity and side effect, improve the therapeutic effect, and exhibit great potential in clinical tumor therapy.

Bacteria-responsive surfaces popularly exert their smart antibacterial activities by bacteria-triggered delivery of antibacterial agents; however, the antibacterial agents should be additionally reloaded for the renewal of these surfaces. Herein, a reversible, nonleaching bacteria-responsive antibacterial surface is prepared by taking advantage of a hierarchical polymer brush architecture. In this hierarchical surface, a pH-responsive poly(methacrylic acid) (PMAA) outer layer serves as an actuator modulating the surface behavior on demand, while antimicrobial peptides (AMP) are covalently immobilized on the inner layer. The PMAA hydration layer renders the hierarchical surface resistant to initial bacterial attachment and biocompatible under physiological conditions. When bacteria colonize the surface, the bacteria-triggered acidification allows the outermost PMAA chains to collapse, therefore exposing the underlying bactericidal AMP to on-demand kill bacteria. In addition, the dead bacteria can be released once the PMAA chains resume their hydrophilicity because of the environmental pH increase. The functionality of the nonleaching surface is reversible without additional reloading of the antibacterial agents. This approach provides a new methodology for the development of smart surfaces in a variety of practical biomedical applications.