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Calcium Bisphosphonate Nanoparticles with Chelator-Free Radiolabeling to Deplete Tumor-Associated Macrophages for Enhanced Cancer Radioisotope Therapy.
ACS Nano 2018 November 28
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 99m Tc for single-photon-emission computed tomography (SPECT) imaging, as well as beta-emitting 32 P as a therapeutic radioisotope for RIT. Upon intravenous injection, CaBP(99m Tc)-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(32 P)-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.
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