Spatiotemporal Controllable Sono-Nanovaccines Driven by Free-Field Based Whole-Body Ultrasound for Personalized Cancer Therapy.

Therapeutic cancer vaccines fail to produce satisfactory outcomes against solid tumors since vaccine-induced anti-tumor immunity is significantly hampered by immunosuppression. Generating an in situ cancer vaccine targeting immunological cold tumor microenvironment (TME) appears attractive. Here, a type of free-field based whole-body ultrasound (US)-driven nanovaccines are constructed, named G5-CHC-R, by conjugating the sonosensitizer, Chenghai chlorin (CHC) and the immunomodulator, resiquimod (R848) on top of a super small-sized dendrimeric nanoscaffold. Once entering tumors, R848 can be cleaved from a hypoxia-sensitive linker, thus modifying the TME via converting macrophage phenotypes. The animals bearing orthotopic pancreatic cancer with intestinal metastasis and breast cancer with lung metastasis are treated with G5-CHC-R under a free-field based whole-body US system. Benefit from the deep penetration capacity and highly spatiotemporal selectiveness, G5-CHC-R triggered by US represented a superior alternative for noninvasive irradiation of deep-seated tumors and magnification of local immune responses via driving mass release of tumor antigens and "cold-warm-hot" three-state transformation of TME. In addition to irradiating primary tumors, a robust adaptive anti-tumor immunity is potentiated, leading to successful induction of systemic tumor suppression. The sono-nanovaccines with good biocompatibility posed wide applicability to a broad spectrum of tumors, revealing immeasurable potential for translational research in oncology.

Leader-laggard synchronization of polarization chaos in mutually coupled free-running VCSELs.

We systematically study the leader-laggard synchronization of polarization chaos in mutually coupled free-running vertical cavity surface emitting semiconductor lasers in two cases of parallel and orthogonal injection. Specifically, we quantitatively investigate the effect of critical external parameter mismatch such as the coupling intensity and frequency detuning on the leader-laggard relationship utilizing the cross-correlation function. When the difference between two main cross-correlation peak values exceeds 0.1, the leader-laggard relationship can be viewed to be stable. Our results demonstrate that compared with the coupling strength, the frequency detuning is the dominant factor in determining the stability of the leader-laggard relationship. The exchange of the leader-laggard role occurs within a frequency detuning region from -5 GHz to 5 GHz for both parallel and orthogonal injection. Once the leader-laggard relationship is stable, the difference between the two cross-correlation values can reach 0.242 for negative frequency detuning, but the corresponding value is only 0.146 under positive frequency detuning.