Laboratory of Advanced Materials, Department of Chemistry, Shanghai Key Lab of Molecular Catalysis and Innovative Materials and State Key Laboratory of Molecular Engineering of Polymers, College of Chemistry and Materials, Fudan University, Shanghai 200433, P. R. China.
Department of Chemistry and Earth Sciences, College of Arts and Sciences, Qatar University, P.O. Box 2713, Doha 2713, Qatar.
ACS Nano. 2024 May 28;18(21):13910-13923. doi: 10.1021/acsnano.4c03652. Epub 2024 May 16.
Thanks to their excellent photoelectric characteristics to generate cytotoxic reactive oxygen species (ROS) under the light-activation process, TiO nanomaterials have shown significant potential in photodynamic therapy (PDT) for solid tumors. Nevertheless, the limited penetration depth of TiO-based photosensitizers and excitation sources (UV/visible light) for PDT remains a formidable challenge when confronted with complex tumor microenvironments (TMEs). Here, we present a HO-driven black TiO mesoporous nanomotor with near-infrared (NIR) light absorption capability and autonomous navigation ability, which effectively enhances solid tumor penetration in NIR light-triggered PDT. The nanomotor was rationally designed and fabricated based on the Janus mesoporous nanostructure, which consists of a NIR light-responsive black TiO nanosphere and an enzyme-modified periodic mesoporous organosilica (PMO) nanorod that wraps around the TiO nanosphere. The overexpressed HO can drive the nanomotor in the TME under catalysis of catalase in the PMO domain. By precisely controlling the ratio of TiO and PMO compartments in the Janus nanostructure, TiO&PMO nanomotors can achieve optimal self-propulsive directionality and velocity, enhancing cellular uptake and facilitating deep tumor penetration. Additionally, by the decomposition of endogenous HO within solid tumors, these nanomotors can continuously supply oxygen to enable highly efficient ROS production under the NIR photocatalysis of black TiO, leading to intensified PDT effects and effective tumor inhibition.
得益于其在光激活过程下生成细胞毒性活性氧（ROS）的优异光电特性，TiO 纳米材料在用于实体瘤的光动力疗法（PDT）方面显示出了巨大的潜力。然而，基于 TiO 的光动力疗法光敏剂和激发源（UV/可见光）的有限穿透深度，在面对复杂的肿瘤微环境（TME）时，仍然是一个巨大的挑战。在这里，我们提出了一种 HO 驱动的具有近红外（NIR）光吸收能力和自主导航能力的黑 TiO 介孔纳米马达，它可以有效地增强 NIR 光触发 PDT 中的实体瘤穿透。该纳米马达是基于 Janus 介孔纳米结构，通过合理设计和制造而成，该结构由一个 NIR 光响应的黑 TiO 纳米球和一个酶修饰的周期性介孔有机硅（PMO）纳米棒组成，纳米棒包裹在 TiO 纳米球周围。过表达的 HO 可以在 PMO 域中的过氧化氢酶的催化下，在 TME 中驱动纳米马达。通过精确控制 Janus 纳米结构中 TiO 和 PMO 隔室的比例，TiO&PMO 纳米马达可以实现最佳的自推进方向性和速度，增强细胞摄取并促进肿瘤深部穿透。此外，通过在实体瘤内分解内源性 HO，这些纳米马达可以不断提供氧气，从而在黑 TiO 的 NIR 光催化下高效地产生 ROS，导致 PDT 效果增强和肿瘤有效抑制。
