Zhang Yijing, Wang Yue, Zhu Anni, Yu Ningyue, Xia Jindong, Li Jingchao
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Biological Science and Medical Engineering, Donghua University, Shanghai, 201620, China.
Department of Radiology, Shanghai Songjiang District Central Hospital, Shanghai, 201600, China.
Angew Chem Int Ed Engl. 2024 Jan 8;63(2):e202310252. doi: 10.1002/anie.202310252. Epub 2023 Dec 6.
Bone metastasis is a type of metastatic tumors that involves the spreads of malignant tumor cells into skeleton, and its diagnosis and treatment remain a big challenge due to the unique tumor microenvironment. We herein develop osteoclast and tumor cell dual-targeting biomimetic semiconducting polymer nanocomposites (SPFeN ) for amplified theranostics of bone metastasis. SPFeN contain semiconducting polymer and iron oxide (Fe O ) nanoparticles inside core and surface camouflaged hybrid membrane of cancer cells and osteoclasts. The hybrid membrane camouflage enables their targeting to both metastatic tumor cells and osteoclasts in bone metastasis through homologous targeting mechanism, thus achieving an enhanced nanoparticle accumulation in tumors. The semiconducting polymer mediates near-infrared (NIR) fluorescence imaging and sonodynamic therapy (SDT), and Fe O nanoparticles are used for magnetic resonance (MR) imaging and chemodynamic therapy (CDT). Because both cancer cells and osteoclasts are killed synchronously via the combinational action of SDT and CDT, the vicious cycle in bone metastasis is broken to realize high antitumor efficacy. Therefore, 4T1 breast cancer-based bone metastasis can be effectively detected and cured by using SPFeN as dual-targeting theranostic nanoagents. This study provides an unusual biomimetic nanoplatform that simultaneously targets osteoclasts and cancer cells for amplified theranostics of bone metastasis.
骨转移是一种转移性肿瘤，涉及恶性肿瘤细胞扩散至骨骼，由于其独特的肿瘤微环境，其诊断和治疗仍然是一个巨大的挑战。我们在此开发了破骨细胞和肿瘤细胞双靶向仿生半导体聚合物纳米复合材料（SPFeN），用于骨转移的放大诊疗。SPFeN的核心包含半导体聚合物和氧化铁（FeO）纳米颗粒，表面伪装着癌细胞和破骨细胞的混合膜。混合膜伪装使其能够通过同源靶向机制靶向骨转移中的转移性肿瘤细胞和破骨细胞，从而实现纳米颗粒在肿瘤中的增强积累。半导体聚合物介导近红外（NIR）荧光成像和声动力疗法（SDT），FeO纳米颗粒用于磁共振（MR）成像和化学动力疗法（CDT）。由于癌细胞和破骨细胞通过SDT和CDT的联合作用被同步杀死，骨转移中的恶性循环被打破，从而实现了高抗肿瘤疗效。因此，使用SPFeN作为双靶向诊疗纳米剂可以有效地检测和治愈基于4T1乳腺癌的骨转移。本研究提供了一种独特的仿生纳米平台，可同时靶向破骨细胞和癌细胞，用于骨转移的放大诊疗。
