Non-cytotoxic nanoparticles re-educating macrophages achieving both innate and adaptive immune responses for tumor therapy

Macrophages are important antigen-presenting cells to combat tumor via both innate and adaptive immunity,while they are programmed toM2 phenotype in established tumors and instead promote cancer development and metastasis.Here,we develop a nanomedicine that can re-educate M2 polarized macrophages to restore their anti-tumor activities.The nanomedicine has a core-shell structure to co-load IPI549,a PI3Kγinhibitor,and CpG,a Toll-like receptor 9 agonist.Specifically,the hydrophobic IPI549 is self-assembled into a pure drug nano-core,while MOF shell layer is coated for CpG encapsulation,achieving extra-high total drugs loading of 44%.Such nanosystem could facilitate intracellular delivery of the payloads but without any cytotoxicity,displaying excellent biocompatibility.After entering macrophages,the released IPI549 and CpG exert a synergistic effect to switch macrophages from M2 to M1 phenotype,which enables anti-tumor activities via directly engulfing tumor cells or excreting tumor killing cytokines.Moreover,tumor antigens released from the dying tumor cells could be effectively presented by the re-educated macrophages owing to the up-regulation of various antigen presenting mediators,resulting in infiltration and activation of cytotoxic T lymphocytes.As a result,the nanosystem triggers a robust antitumor immune response in combination with PD-L1 antibody to inhibit tumor growth and metastasis.This work provides a non-cytotoxic nanomedicine to modulate tumor immune microenvironment by reprograming macrophages.

Resonant Modes of One-Dimensional Metamaterial Containing Helmholtz Resonators with Point Defect

The metamaterial constructed by Helmholtz resonators (HR) has low-frequency acoustic forbidden bands and possesses negative mass density and effective bulk modulus at particular frequencies. The resonant modes in one-dimensional HR structure with point defect were studied using finite element method (FEM). The results show that the acoustic energy is localized between the resonant HR and the opening in the local-resonant-type gap. There is a high pressure area around the defect resonator at the frequency of defect mode. In the Bragg type gap, the energy mainly distributes in the waveguide with harmonic attenuation due to the multi-scattering. Phase opposition demonstrates the existence of negative dynamic mass density. Local negative parameter is observed in the pass band due to the defect mode. Based on further investigation of the acoustic intensity and phase distributions in the resonators corresponding to two different forbidden bands, only one local resonant mode is verified, which is different from the three-component local resonant phononics. This work will be useful for understanding the mechanisms of acoustic forbidden bands and negative parameters in the HR metamaterial, and of help for designing new functional acoustic devices.