¹³¹I-labeled And DOX-loaded Multifunctional Nanoliposomes For Radiotherapy And Chemotherapy In Brain Gliomas

Introduction: Gliomas are the most common type of primary intracranial tumors and are characterized by significant mortality and morbidity. The prognosis for patients is generally poor. To enhance treatment effectiveness, many approaches have been studied, but all of them are still in the experimental stage. The codelivery of different therapeutics is a promising option because of its improved therapeutic effectiveness via the synergetic effects of drugs. Fortunately, nanoparticles provide a new impetus for cancer therapy due to its unique physical properties.Methods: In this study, a new combination therapy that used the doxorubicin-loaded and 131-labeled nanoliposomes (¹³¹I-DOX-NL) was proposed.¹³¹I-DOX-NL was constructed based on bovine serum albumin ?BSA?-tailor made hydrophobic maleimide-functionalized poly??-caprolactone? ?PCL? and was evaluated by cellular viability in vitro and by a U87 xenograft model in vivo. ¹³¹I-labeled nanoliposomes (¹³¹I-NL) and doxorubicin-loaded nanoliposomes ?DOX-NL? were also constructed and used as control groups. The cellular uptake of DOX-NL, ¹³¹I-NL and ¹³¹I-DOX-NL was measured by flow cytometry. The cytotoxicity of ¹³¹I-DOX-NL, ¹³¹I-NL and DOX-NL was measured by MTS assay. Further, the nanoparticle was decorated with cRGD petide to enhance the ability to target the tumor cells. And we used MTS assay measured the treatment effectiveness of cRGD-¹³¹I-DOX-NL. The in vivo bio-distribution analysis was performed by calculating the percentage of the injected dose per gram of tissue ?%ID/g?. The antitumor effects were evaluated in terms of the tumor growth rate and animal survival time in U87 bearing mice. Toxicology studies were performed by observing the histopathology of major organs ex vivo and the spiritual condition of the mice.Finally, the U87 xenograft model was imaged by SPECT/CT.Results: The cellular uptake rates of DOX-NL, ¹³¹I-NL and ¹³¹I-DOX-NL were higher than those of the control group after a 4-hour incubation. The MTS assay showed that the cytotoxicity of ¹³¹I-DOX-NL was more significant than that of ¹³¹I-NL and DOX-NL. Compared with the ¹³¹I-DOX-NL group, the cRGD-¹³¹I-DOX-NL conjugate nanoparticle showed enhanced cell uptake ?P<0.001?and better therapeutic efficacy in MTS assay. The tissue distribution assay revealed that the tumor markedly took up ¹³¹I-DOX-NL and had accumulated more radioactive ¹³¹I than the Na¹³¹I control group. Tumor size measurements showed that tumor growth was significantly inhibited by treatment with ¹³¹I-DOX-NL, while the tumors of the control groups grew more rapidly. The mice had an extended median survival time of 45 days, with no serious body weight loss. Furthermore, no acute toxicity during the regimen in the ¹³¹I-DOX-NL group which were proved in the H&E stain.The SPECT/CT showed that ¹³¹I-DOX-NL was retained in the tumor, while the Na¹³¹I was quickly rejected from tumors.Conclusion: Multifunctional nanoliposome¹³¹I-DOX-NL is a good candidate for the codelivery of ¹³¹I-mediated radiotherapy and DOX-mediated chemotherapy due to its ability to inhibit U87 cell proliferation and tumor growth. As a result,¹³¹I-DOX-NL could be used as a promising effective therapy for malignant gliomas.The decortated targeted ligand ?cRGD peptide? nanoparticles enhanced the cell uptake and better therapeutic efficacy in U87 cell.