Abstract
Molecular imaging used in cancer diagnosis and therapeutic response monitoring is important for glioblastoma (GBM) research. Antiangiogenic therapy currently is one of the emerging approaches for GBM treatment. In this study, a multifunctional nanoparticle was fabricated that can facilitate the fluorescence imaging of tumor and deliver a therapeutic agent to the tumor region in vivo and therefore possesses broad application in cancer diagnosis and treatment. This particle was polylactic acid (PLA) nanoparticles encapsulating Endostar, which was further conjugated with GX1 peptide and the near-infrared (NIR) dye IRDye 800CW (IGPNE). We demonstrated noninvasive angiogenesis targeting and therapy of IGPNE on U87MG xenografts in vivo using dual-modality optical molecular imaging including NIR fluorescence molecular imaging (FMI) and bioluminescence imaging (BLI). The NIR FMI results demonstrated that IGPNE had more accumulation to the tumor site compared to free IRDye 800CW. To further evaluate the antitumor treatment efficacy of IGPNE, BLI and immunohistochemistry analysis were performed on tumor-bearing mice. With the aid of molecular imaging, the results confirmed that IGPNE enhanced antitumor treatment efficacy compared to free Endostar. In conclusion, IGPNE realizes real-time imaging of U87MG tumors and improves the antiangiogenic therapeutic efficacy in vivo.
Highlights
Molecular imaging used in cancer diagnosis and therapeutic response monitoring is important for glioblastoma (GBM) research
The results suggest that IGPNE is a potential targeted and long-acting formulation of Endostar that may contribute to enhanced antiangiogenesis therapy of GBM
The results suggest that the GX1 peptide facilitated Endostar accumulation at the tumor regions and that IGPNE acquired the capability of controlled drug release at tumor sites
Summary
Molecular imaging used in cancer diagnosis and therapeutic response monitoring is important for glioblastoma (GBM) research. A multifunctional nanoparticle was fabricated that can facilitate the fluorescence imaging of tumor and deliver a therapeutic agent to the tumor region in vivo and possesses broad application in cancer diagnosis and treatment This particle was polylactic acid (PLA) nanoparticles encapsulating Endostar, which was further conjugated with GX1 peptide and the near-infrared (NIR) dye IRDye 800CW (IGPNE). Endostar has been investigated clinically combined with the first-line chemotherapy regimen in patients with advanced non–small cell lung cancer and has been demonstrated to inhibit the growth of a variety of human tumors by inhibiting neovascularization and to be superior to other recombinant endostatins.[26,27] Continuous subcutaneous administration of endostatin resulted in inhibiting the growth of U87MG (a human neuronal GBM cell line) tumors in a tumorbearing mouse model as reported.[25,28,29] despite its apparent therapeutic value, the biological half-life of Endostar in vivo is short due to its rapid metabolism, similar to most protein drugs.[30] a long-acting and more stable formulation of Endostar is expected
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