题目： | Calcium Bisphosphonate Nanoparticles with Chelator-Free Radiolabeling to Deplete Tumor-Associated Macrophages for Enhanced Cancer Radioisotope Therapy |
作者： | Longlong Tian,1 Xuan Yi,2 Ziliang Dong,1 Jun Xu,1 Chao Liang,1 Yu Chao,1 Yaxing Wang,2 Kai Yang,2,* and Zhuang Liu1,* |
单位： | 1Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, Jiangsu 215123, China 2State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection & School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, Jiangsu 215123, China |
摘要： | Tumor-associated macrophages (TAMs) are often related with poor prognosis after radiotherapy. Depleting TAMs may thus be a promising method to improve the radio-therapeutic efficacy.Herein, we report a biocompatible and biodegradable nanoplatform based on calcium bisphosphonate (CaBP-PEG) nanoparticles for chelator-free radiolabeling chemistry, effective in vivo depletion of TAMs, and imaging-guided enhanced cancer radioisotope therapy (RIT). It is found that CaBP-PEG nanoparticles prepared via a mineralization method with poly(ethylene glycol) (PEG) coating could be labeled with various radioisotopes upon simple mixing, including gamma emitting 99mTc for single-photon-emission computed tomography (SPECT) imaging, as well as beta-emitting 32P as a therapeutic radioisotope for RIT. Upon intravenous injection, CaBP(99mTc)-PEG nanoparticles exhibit efficient tumor homing, as evidenced by SPECT imaging. Owning to the function of bisphosphonates as clinical drugs to deplete TAMs, suppressed angiogenesis, normalized tumor vasculatures, enhanced intratumoral perfusion, and relieved tumor hypoxia are observed after TAM depletion induced by CaBP-PEG. Such modulated tumor microenvironment appears to be highly favorable for cancer RIT using CaBP(32P)-PEG as the radio-therapeutic agent, which offers excellent synergistic therapeutic effect in inhibiting the tumor growth. With great biocompatibility and multifunctionalities, such CaBP-PEG nanoparticles constituted by Ca2+ and a clinical drug would be rather attractive for clinical translation. |
影响因子： | 13.709 |
分区情况： | 一区 |
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