Nanoparticles for Stem Cell Therapy Bioengineering in Glioma

Abstract

Gliomas are a dismal disease associated with poor survival and high morbidity. Current standard treatments have reached a therapeutic plateau even after combining maximal safe resection, radiation, and chemotherapy. In this setting, stem cells (SCs) have risen as a promising therapeutic armamentarium, given their intrinsic tumor homing as well as their natural or bioengineered antitumor properties. The interplay between stem cells and other therapeutic approaches such as nanoparticles holds the potential to synergize the advantages from the combined therapeutic strategies. Nanoparticles represent a broad spectrum of synthetic and natural biomaterials that have been proven effective in expanding diagnostic and therapeutic efforts, either used alone or in combination with immune, genetic, or cellular therapies. Stem cells have been bioengineered using these biomaterials to enhance their natural properties as well as to act as their vehicle when anticancer nanoparticles need to be delivered into the tumor microenvironment in a very precise manner. Here, we describe the recent developments of this new paradigm in the treatment of malignant gliomas.

Novel Strategies for Nanoparticle-Based Radiosensitization in Glioblastoma

“…This is possible given that NP with diameters of at least 5–10 nm have reduced kidney excretion different from conventional chemotherapeutics. They are usually <1 kDa and filter more easily through the kidney [ 23 ]. Consequently, these particles have enough time to move from the bloodstream into the tumor tissue.…”

“…Active targeting refers to the process that allows NP to selectively distribute into specific cell types or even intracellular compartments ( Figure 1 B) [ 23 ]. This involves the design of specific moieties for NP biofunctionalization.…”

“…One of these methods is known as ligand targeting, this involves the selection and designing of specific ligands which will bind to the NP surface (biofunctionalization) to mediate the precise interaction between NP and the desired target cell [ 23 ]. This interaction between the ligand and the cell happen through cellular receptors/membrane proteins that may or may not lead to cellular internalization [ 34 ].…”

“…However, although these non-antibody ligands enhance target specificity, they can still bind some non-target tissues as well as compete for the target receptor with free ligands, such as folate, that can also come from diet and reach high levels in plasma [ 34 ]. Any of the previously mentioned ligands can be directly or indirectly (i.e., after PEGylation) linked to the NP, and thus target cancer cells, tumor stromal cells, or tumor blood vessels [ 23 ].…”

Knockdown of DNA polymerase ζ relieved the chemoresistance of glioma via inhibiting the PI3K/AKT signaling pathway

“…In recent years, glioma has become one of the most commonly diagnosed types of cancer worldwide [1][2][3]. With the recurrence and metastasis ability of cancer cells, the number of patients diagnosed with malignant glioma is increasing [3][4][5]. Current anti-glioma therapies include chemotherapy and surgery, and previous research has shown that chemotherapy can improve the lifespan and quality of life of most glioma patients [6,7].…”