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.