Acid-switchable nanoparticles induce self-adaptive aggregation for enhancing antitumor immunity of natural killer cells

Deficiency of natural killer(NK)cells shows a significant impact on tumor progression and failure of immunotherapy.It is highly desirable to boost NK cell immunity by upregulating active receptors and relieving the immunosuppressive tumor microenvironment.Unfortunately,mobilization of NK cells is hampered by poor accumulation and short retention of drugs in tumors,thus declining antitumor efficiency.Herein,we develop an acid-switchable nanoparticle with self-adaptive aggregation property for co-delivering galunisertib and interleukin 15(IL-15).The nanoparticles induce morphology switch by a decomposition-metal coordination cascade reaction,which provides a new methodology to trigger aggregation.It shows self-adaptive size-enlargement upon acidity,thus improving drug retention in tumor to over 120 h.The diameter of agglomerates is increased and drug release is effectively promoted following reduced p H values.The nanoparticles activate both NK cell and CD8+T cell immunity in vivo.It significantly suppresses CT26 tumor in immune-deficient BALB/c mice,and the efficiency is further improved in immunocompetent mice,indicating that the nanoparticles can not only boost innate NK cell immunity but also adaptive T cell immunity.The approach reported here provides an innovative strategy to improve drug retention in tumors,which will enhance cancer immunotherapy by boosting NK cells.

Cylindrical vector beam revealing multipolar nonlinear scattering for superlocalization of silicon nanostructures

The resonant optical excitation of dielectric nanostructures offers unique opportunities for developing remarkable nanophotonic devices.Light that is structured by tailoring the vectorial characteristics of the light beam provides an additional degree of freedom in achieving flexible control of multipolar resonances at the nanoscale.Here,we investigate the nonlinear scattering of subwavelength silicon(Si)nanostructures with radially and azimuthally polarized cylindrical vector beams to show a strong dependence of the photothermal nonlinearity on the polarization state of the applied light.The resonant magnetic dipole,selectively excited by an azimuthally polarized beam,enables enhanced photothermal nonlinearity,thereby inducing large scattering saturation.In contrast,radially polarized beam illumination shows no observable nonlinearity owing to off-resonance excitation.Numerical analysis reveals a difference of more than 2 orders of magnitude in photothermal nonlinearity under two types of polarization excitations.Nonlinear scattering and the unique doughnut-shaped focal spot generated by the azimuthally polarized beam are demonstrated as enabling far-field high-resolution localization of nanostructured Si with an accuracy approaching 50 nm.Our study extends the horizons of active Si photonics and holds great potential for label-free superresolution imaging of Si nanostructures.