Silica hollow spheres（SHSs） have attracted great attention because of their low toxicity, low density, large surface area, high chemical and thermal stability, and surface permeability. They can be widely applied in storage^[l], catalysis^[2], drug deli- very^[3,4], low-dielectric-constant materials^[5], low-refractive materials^[6-8], and so on. Up to now, there have been various methods to produce SHSs. Inorganic^[9] or organic particles^[10], such as polystyrene or calcium carbonate, were used as hard templates to create hollow cavities, However, the multistep synthetic process and the lack of structural robustness of the shells upon template removal process weaken their applica- tion. Soft templates, including oil-in-water emulsions^[11,12], vesicles^[13], micelle^[14,15] and gas bubbles^[16], are applied widely.
Tumor microvasculature is important to tumor growth, metastasis and thus tumor treatment outcome. The alternate cooling and heating treatment has been confirmed to have advantages over single treatment of cooling or heating. The degree of tumor microvasculature damage induced by the alternate cooling and heating treatment and the mechanisms underlying are studied in this paper. The response of the tumor microvasculature to different treatments including alternate cooling and heating is observed in vivo through confocal microscopy using the nude mice dorsal skin fold tumor chamber model. Results show that alternate cooling and heating has induced much more severe damage to the microvessel structure throughout the entire tumor. Numerical simulations of the mechanical stresses on the tumor vessel wall has found that during the alternate treatment, the vessel wall suffer a rapid chang in thermal stresses in the opposite directions successively, which might caused damage to the peripheral microvasculature and micro-cracks in the central vessels. Reperfusion of blood flow after freezing also led to relatively large stresses on the vessel wall, especially when blood flow re-perfuses quickly during the subsequent heating. The quick increase of stresses on the blood vessel might be one of the key issues causing the blood vessel rupture referring to the experimental observation. The preliminary study has partly revealed the mechanism underlying serious tumor microvasculature damage caused by the alternate cooling and heating treatment.
