Targeting DNA-PKcs promotes anti-tumoral immunity via triggering cytosolic DNA sensing and inducing an inflamed tumor immuno-microenvironment in metastatic triple-negative breast cancer

Triple-negative breast cancer(TNBC)is highly malignant and refractory to immunotherapy through impeding the immune cell infiltration and inflammation in the tumor microenvironment(TME).1 DNA-dependent protein kinase catalytic subunit(DNA-PKcs)is a member of the phosphatidylinositol 3-kinase-related kinase family,which is required for the non-homologous end joining repair.2 The effect of DNA-PKcs on the generation of cytosolic DNA and inflammation response in tumor immuno-environment is not defined.We found a specific DNA-PKcs inhibitor,NU7441,induced cytosolic DNA,stimulator of interferon genes(STING),and retinoic acid-inducible gene I(RIG-I)signals in vitro.In Balb/c immune-competent mice bearing 4T1 TNBC cells,NU7441 impaired the tumor growth and metastasis,and increased the CD45+leukocytes,CD4+T cells,CD8+T cells,and CD1a+antigen-presenting cells,as well as MHC-I and interferon alpha receptor(IFNAR)in TME.However,in Balb/c athymic nude mice without IFNAR and CD8+T cells in TME,NU7741 did not influence tumor growth.These results show that inhibition of DNA-PKcs triggers cytosolic DNA sensing and induces an inflamed TME to promote anti-tumoral immunity,which provides a strategy to alter the inflammation and lymphocyte infiltration in TME to increase the efficacy of immunotherapy in TNBC and other cancers with an immune-suppressive TME.

Biomembrane-inspired design of medical micro/nanorobots:From cytomembrane stealth cloaks to cellularized Trojan horses

Micro/nanorobots are promising for a wide range of biomedical applications(such as targeted tumor,thrombus,and infection therapies in hard-to-reach body sites)because of their tiny size and high maneuverability through the actuation of external fields(e.g.,magnetic field,light,ultrasound,electric field,and/or heat).However,fully synthetic micro/nanorobots as foreign objects are susceptible to phagocytosis and clearance by diverse phagocytes.To address this issue,researchers have attempted to develop various cytomembrane-camouflaged micro/nanorobots by two means:(1)direct coating of micro/nanorobots with cytomembranes derived from living cells and(2)the swallowing of micro/nanorobots by living immunocytes via phagocytosis.The camouflaging with cytomembranes or living immunocytes not only protects micro/nanorobots from phagocytosis,but also endows them with new characteristics or functionalities,such as prolonging propulsion in biofluids,targeting diseased areas,or neutralizing bacterial toxins.In this review,we comprehensively summarize the recent advances and developments of cytomembrane-camouflaged medical micro/nanorobots.We first discuss how cytomembrane coating nanotechnology has been employed to engineer synthetic nanomaterials,and then we review in detail how cytomembrane camouflage tactic can be exploited to functionalize micro/nanorobots.We aim to bridge the gap between cytomembrane-cloaked micro/nanorobots and nanomaterials and to provide design guidance for developing cytomembrane-camouflaged micro/nanorobots.

Absorption and scattering effects of Maalox,chlorophyll, and sea salt on a micro-LED-based underwater wireless optical communication [Invited]

In this work,a blue gallium nitride(GaN)micro-light-emitting-diode(micro-LED)-based underwater wireless optical communication(UWOC)system was built,and UWOCs with varied Maalox,chlorophyll,and sea salt concentrations were studied.Data transmission performance of the UWOC and the influence of light attenuation were investigated systematically.Maximum data transmission rates at the distance of 2.3 m were 933,800,910,and 790 Mbps for experimental conditions with no impurity,200.48 mg/m3 Maalox,12.07 mg/m3 chlorophyll,and 5 kg/m3 sea salt,respectively,much higher than previously reported systems with commercial LEDs.It was found that increasing chlorophyll,Maalox,and sea salt concentrations in water resulted in an increase of light attenuation,which led to the performance degradation of the UWOC.Further analysis suggests two light attenuation mechanisms,e.g.,absorption by chlorophyll and scattering by Maalox,are responsible for the decrease of maximum data rates and the increase of bit error rates.Based on the absorption and scattering models,excellent fitting to the experimental attenuation coefficient can be achieved,and light attenuation by absorption and scattering at different wavelengths was also investigated.We believe this work is instructive apply UWOC for practical applications.

Influence of light pattern thickness on the manipulation of dielectric microparticles by optoelectronic tweezers

Optoelectronic tweezer(OET) is a useful optical micromanipulation technology that has been demonstrated for various applications in electrical engineering and most notably cell selection for biomedical engineering. In this work, we studied the use of light patterns with different shapes and thicknesses to manipulate dielectric microparticles with OET. It was demonstrated that the maximum velocities of the microparticles increase to a peak and then gradually decrease as the light pattern’s thickness increases. Numerical simulations were run to clarify the underlying physical mechanisms, and it was found that the observed phenomenon is due to the co-influence of horizontal and vertical dielectrophoresis forces related to the light pattern’s thickness. Further experiments were run on light patterns with different shapes and objects with different sizes and structures. The experimental results indicate that the physical mechanism elucidated in this research is an important one that applies to different light pattern shapes and different objects, which is useful for enabling users to optimize OET settings for future micromanipulation applications.