Photodynamic Therapy For Glioblastoma Research Articles

Cross‐Scale Drug Delivery of Diatom Microrobots Based on A Magnetic Continuum Robot for Combined Chemical and Photodynamic Therapy of Glioblastoma

AbstractMicro/nanorobots with active movement capabilities provide a new option for the treatment of glioblastoma (GBM). However, the long working distance of intravenous injection and the protection of the blood‐brain barrier can prevent micro/nanorobots from reaching the target location. Photodynamic therapy (PDT) has gradually appeared in GBM treatment research. The limitation of the penetrating strength of the light source will nevertheless hinder the application range of PDT. Herein, a magnetic continuum robot (MCR) to deliver optical fibers and microrobots for combined chemotherapy and PDT of GBM is used. The prepared magnetic diatom microrobots can effectively move in biological fluids and move upstream. Vacuum loading can improve the drug loading efficiency. The photosensitizer in the frustule cavity can be explosively released in a short time through ultrasound. The chemotherapeutic drugs have long‐term and pH‐sensitivity release characteristics. In vitro cell experiments showed that the combined administration of TMZ‐loaded microrobots and photosensitizer‐loaded microrobots has a synergistic effect. The in vitro model demonstrated that an MCR can deliver an optical fiber and drug‐loaded microrobots. This enables cross‐scale delivery of microrobots and deep PDT. This delivery method may expand the drug selectivity for GBM treatment and provide a new possibility for intracranial PDT.

New Crystal Form of Human Neuropilin-1 b1 Fragment with Six Electrostatic Mutations Complexed with KDKPPR Peptide Ligand.

Neuropilin 1 (NRP1), a cell-surface co-receptor of a number of growth factors and other signaling molecules, has long been the focus of attention due to its association with the development and the progression of several types of cancer. For example, the KDKPPR peptide has recently been combined with a photosensitizer and a contrast agent to bind NRP1 for the detection and treatment by photodynamic therapy of glioblastoma, an aggressive brain cancer. The main therapeutic target is a pocket of the fragment b1 of NRP1 (NRP1-b1), in which vascular endothelial growth factors (VEGFs) bind. In the crystal packing of native human NRP1-b1, the VEGF-binding site is obstructed by a crystallographic symmetry neighbor protein, which prevents the binding of ligands. Six charged amino acids located at the protein surface were mutated to allow the protein to form a new crystal packing. The structure of the mutated fragment b1 complexed with the KDKPPR peptide was determined by X-ray crystallography. The variant crystallized in a new crystal form with the VEGF-binding cleft exposed to the solvent and, as expected, filled by the C-terminal moiety of the peptide. The atomic interactions were analyzed using new approaches based on a multipolar electron density model. Among other things, these methods indicated the role played by Asp320 and Glu348 in the electrostatic steering of the ligand in its binding site. Molecular dynamics simulations were carried out to further analyze the peptide binding and motion of the wild-type and mutant proteins. The simulations revealed that specific loops interacting with the peptide exhibited mobility in both the unbound and bound forms.

Photodynamic Therapy for Glioblastoma: Illuminating the Path toward Clinical Applicability.

Glioblastoma (GBM) is the most common adult brain cancer. Despite extensive treatment protocols comprised of maximal surgical resection and adjuvant chemo-radiation, all glioblastomas recur and are eventually fatal. Emerging as a novel investigation for GBM treatment, photodynamic therapy (PDT) is a light-based modality that offers spatially and temporally specific delivery of anti-cancer therapy with limited systemic toxicity, making it an attractive option to target GBM cells remaining beyond the margins of surgical resection. Prior PDT approaches in GBM have been predominantly based on 5-aminolevulinic acid (5-ALA), a systemically administered drug that is metabolized only in cancer cells, prompting the release of reactive oxygen species (ROS), inducing tumor cell death via apoptosis. Hence, this review sets out to provide an overview of current PDT strategies, specifically addressing both the potential and shortcomings of 5-ALA as the most implemented photosensitizer. Subsequently, the challenges that impede the clinical translation of PDT are thoroughly analyzed, considering relevant gaps in the current PDT literature, such as variable uptake of 5-ALA by tumor cells, insufficient tissue penetrance of visible light, and poor oxygen recovery in 5-ALA-based PDT. Finally, novel investigations with the potential to improve the clinical applicability of PDT are highlighted, including longitudinal PDT delivery, photoimmunotherapy, nanoparticle-linked photosensitizers, and near-infrared radiation. The review concludes with commentary on clinical trials currently furthering the field of PDT for GBM. Ultimately, through addressing barriers to clinical translation of PDT and proposing solutions, this review provides a path for optimizing PDT as a paradigm-shifting treatment for GBM.

Photodynamic therapy for glioblastoma: A light at the end of the tunnel

Glioblastomas (GBM) are considered one of the most aggressive tumors of the central nervous system. The standard treatment for GBM-diagnosed patients implies surgery, followed by radio and chemotherapy, with a survival of 12 to 15 months after treatment. Photodynamic Therapy (PDT) is an alternative approach to treating several diseases, including tumors. The study of PDT to treat GBM has been gaining attention over the last few years. In this work, we reviewed the cellular and molecular features and current treatment modalities for GBM as well as the most used photosensitizers for GBM-PDT reported in the last five years, such as porphyrins, chlorins, and phthalocyanines, and also their precursors, as in the case of aminolaevulinic acid. Moreover, an analysis of cellular targets, mechanisms mediating the response and resistance to PDT, and clinical application of this strategy for GBM treatment have been discussed.

Photodynamic therapy for glioblastoma: A preliminary approach for practical application of light propagation models.

Photodynamic therapy (PDT) is a promising treatment modality to be added in the management of glioblastoma multiforme (GBM). Light distribution modeling is required for planning and optimizing PDT. Several models have been developed to predict the light propagation inside biological tissues. In the present study, two analytical methods of light propagation emitted from a cylindrical fiber source were evaluated: a discrete and a continuous method. The two analytical approaches were compared according to their fluence rate results. Several cylindrical diffuse lengths were evaluated, and the relative deviation in the fluence rates was estimated. Moreover, a sensitivity analysis was conducted to compute the variance of each analytical model. The discrete method provided fluence rate estimations closer to the Monte-Carlo simulations than the continuous method. The sensitivity study results did not reveal significant differences between the variance of the two analytical models. Although the discrete model provides relevant light distribution, the heterogeneity of GBM tissues was not considered. With the improvement in parallel computing that drastically decreased the computing time, replacing the analytical model by a Monte-Carlo GPU-accelerated code appeared relevant to the GBM case. Nonetheless, the analytical modeling may still function in the optimization algorithms, which might be used in the Photodynamic treatment planning system. Lasers Surg. Med. 50:523-534, 2018. © 2017 Wiley Periodicals, Inc.

Use of diffusion MR imaging and proton MR spectroscopy imaging monitoring to predict tumor response to interstitial photodynamic therapy for glioblastoma

Use of diffusion MR imaging and proton MR spectroscopy imaging monitoring to predict tumor response to interstitial photodynamic therapy for glioblastoma