Phototheranostics: Active Targeting of Orthotopic Glioma Using Biomimetic Proteolipid Nanoparticles

Abstract

Advances in phototheranostics revolutionized glioma intraoperative fluorescence imaging and phototherapy. However, the lack of desired active targeting agents for crossing the blood–brain barrier (BBB) significantly compromises the theranostic efficacy. In this study, biomimetic proteolipid nanoparticles (NPs) with U.S. Food and Drug Administration (FDA)-approved indocyanine green (ICG) were constructed to allow fluorescence imaging, tumor margin detection, and phototherapy of orthotopic glioma in mice. By embedding glioma cell membrane proteins into NPs, the obtained biomimetic ICG-loaded liposome (BLIPO-ICG) NPs could cross BBB and actively reach glioma at the early stage thanks to their specific binding to glioma cells due to their excellent homotypic targeting and immune escaping characteristics. High accumulation in the brain tumor with a signal to background ratio of 8.4 was obtained at 12 h post-injection. At this time point, the glioma and its margin were clearly visualized by near-infrared fluorescence imaging. Under the imaging guidance, the glioma tissue could be completely removed as a proof of concept. In addition, after NIR laser irradiation (1 W/cm2, 5 min), the photothermal effect exerted by BLIPO-ICG NPs efficiently suppressed glioma cell proliferation with a 94.2% tumor growth inhibition. No photothermal damages of normal brain tissue and treatment-induced side effects were observed. These results suggest that the biomimetic proteolipid NP is a promising phototheranostic nanoplatform for brain-tumor-specific imaging and therapy.

Camouflaging Nanoparticles with Brain Metastatic Tumor Cell Membranes: A New Strategy to Traverse Blood–Brain Barrier for Imaging and Therapy of Brain Tumors

“…Some literatures reported that although the tight junctions of BBB are slightly disrupted in the early stage of glioma, most nanomaterials cannot traverse the BBB to accumulate in glioma for early diagnosis and therapy. [ 8,21,22 ] In order to explore whether the metastatic cancer cell membrane‐coated nanoparticles can cross the BBB to image glioma tumor cells in the early stage, an orthotopic mouse model bearing luciferase‐expressing human glioblastoma tumor (U87MG‐Luc) was used to perform the analysis. The glioma cell activity was measured by bioluminescence imaging.…”

“…The rapid growth of glioma cells into the brain can disrupt the BBB severely. [ 21 ] At 4 h after the injection of these nanoparticles, the fluorescence signals in the glioma site were found in all samples, indicating that all the four kinds of nanoparticles can diffuse through the disrupted BBB and enter into mice brains (a). This was owing to the enhanced permeability and retention effect.…”

“…After 5 min of laser irradiation (1 W cm −2 ), the temperature of tumor site of B16‐PCL‐ICG treated mice reached 48 °C, which exceeded the damage threshold value (42 °C) and resulted in irreversible tissue damage (Figure S15, Supporting Information). [ 14,21 ] In contrast, the temperature of tumor site of mice treated with COS7‐PCL‐ICG only rose to 39.8 °C, because of its poor BBB penetration and tumor accumulation. Bioluminescence imaging was applied to visualize the anti‐tumor effect of B16‐PCL‐ICG.…”

“…Although some cell membrane camouflaged nanoparticles have been applied for imaging and photoactivatable therapy in various cancer models, [ 18–20 ] the feasibility of using this strategy in the treatment of brain related diseases has rarely been explored. [ 21 ]…”

Cell Membrane Nanotherapeutics: From Synthesis to Applications Emerging Tools for Personalized Cancer Therapy

“…A further application of cell‐membrane coated nanomaterials is their use as highly specific imaging probes and contrasting agents. [ 96,134,141–144 ] Due to cancer cell membrane's homotypic targeting capabilities, CMNs can be used for detecting cancer with enhanced fluorescent imaging, contrasting, and detection capabilities because of lower nonspecific tissue accumulation. Fluorescent imaging is a preferred choice of imaging in biological applications but often lacks sufficient penetration depth due to the absorption and scattering of excitation light by water.…”