Photothermal treatment of glioma; an in vitro study of macrophage-mediated delivery of gold nanoshells

Abstract

One of the major factors that limits the treatment effectiveness for gliomas is the presence of the blood–brain barrier (BBB) which protects infiltrating glioma cells from the effects of anti-cancer agents. Circulating monocytes/macrophages (Ma) have a natural ability to traverse the intact and compromised BBB and loaded with anti cancer agents could be used as vectors to target tumors and surrounding tumor infiltrated tissue. Nanoshells (NS) are composed of a dielectric core (silica) coated with an ultrathin gold layer which converts absorbed near-infrared light (NIR) to heat with an extremely high efficacy and stability. We have investigated the effects of exposure to laser NIR on multicell human glioma spheroids infiltrated with empty (containing no nanoshells) or nanoshell loaded macrophages. Our results demonstrated that; (1) macrophages could efficiently take up bare or coated (PEGylated) gold NS: (2) NS loaded macrophages infiltrated into glioma spheroids to the same or, in some cases, to a greater degree than empty Ma; (3) NIR laser irradiation of spheroids incorporating NS loaded macrophages resulted in complete growth inhibition in an irradiance dependent manner, and (4) spheroids infiltrated with empty macrophages had growth curves identical to untreated control cultures. The results of this study provide proof of concept for the use of macrophages as a delivery vector of NS into gliomas for photothermal ablation and open the possibility of developing such regimens for patient treatment.

Magnetic resonance–guided laser interstitial thermal therapy: report of a series of pediatric brain tumors

“…37,38 The addition of MRgLITT to nanotechnology may be of great value to nanoparticle-enhanced ablation treatments and enable much deeper optical penetration into the tumor. 1,20,24 Magnetic resonance-guided LITT systems are expected to evolve and be compatible with robotic and computerized simulation applications. Upgrades should include improved tools for planning and insertion, volumetric MR-guided ablation monitoring, and tuning optimal temperature limits.…”

Human cytotoxic T-lymphocyte membrane-camouflaged nanoparticles combined with low-dose irradiation: a new approach to enhance drug targeting in gastric cancer

“…[15][16][17] The concept of using cells as drug delivery vehicles is rapidly developing. [18][19][20] The use of natural cellular membranes to camouflage synthetic polymeric nanoparticles has demonstrated significant potential. [21][22][23][24][25] In this study, the membranes of human cytotoxic T lymphocytes (hCTLs) were chosen to produce cancer-targeting nanoparticles, because of the long blood circulation time and the ability to recruit and localize at tumor sites, of this cell type.…”

In vivo photothermal treatment by the peritumoral injection of macrophages loaded with gold nanoshells

“…Photothermal treatment (PTT) aims to destroy cancers by converting photon energy into heat via nanoparticles [1][2][3][4][5]. In recent years, interest in PTT has increased due to the development of novel nanoparticles with improved target specificities and heat conversion efficiencies.…”