Nanoparticles for Drug and Gene Delivery in Pediatric Brain Tumors’ Cancer Stem Cells: Current Knowledge and Future Perspectives

Abstract

Primary malignant brain tumors are the most common solid neoplasm in childhood. Despite recent advances, many children affected by aggressive or metastatic brain tumors still present poor prognosis, therefore the development of more effective therapies is urgent. Cancer stem cells (CSCs) have been discovered and isolated in both pediatric and adult patients with brain tumors (e.g., medulloblastoma, gliomas and ependymoma). CSCs are a small clonal population of cancer cells responsible for brain tumor initiation, maintenance and progression, displaying resistance to conventional anticancer therapies. CSCs are characterized by a specific repertoire of surface markers and intracellular specific pathways. These unique features of CSCs biology offer the opportunity to build therapeutic approaches to specifically target these cells in the complex tumor bulk. Treatment of pediatric brain tumors with classical chemotherapeutic regimen poses challenges both for tumor location and for the presence of the blood–brain barrier (BBB). Lastly, the application of chemotherapy to a developing brain is followed by long-term sequelae, especially on cognitive abilities. Novel avenues are emerging in the therapeutic panorama taking advantage of nanomedicine. In this review we will summarize nanoparticle-based approaches and the efficacy that NPs have intrinsically demonstrated and how they are also decorated by biomolecules. Furthermore, we propose novel cargoes together with recent advances in nanoparticle design/synthesis with the final aim to specifically target the insidious CSCs population in the tumor bulk.

Recent Advances in Nanomaterials-Based Targeted Drug Delivery for Preclinical Cancer Diagnosis and Therapeutics

“…Depending on the amount of CD66c expression, breast CSCs on treatment with CD66c Ab-conjugated rhodamine-labeled liposomes (CDRHOL) indicated selective and enhanced cellular absorption [182]. Researchers have demonstrated that nanoparticle-based curcumin delivery has enhanced its bioavailability and resulted in the eradication of CD133 + CSCs, thereby inhibiting the growth of brain tumors [183]. The overexpression of CD133 in CSCs of osteosarcoma has been targeted by the application of CD133 aptamers conjugated with salinomycin loaded PLGA nanoformulations [184].…”

Cancer Stem Cells in Tumours of the Central Nervous System in Children: A Comprehensive Review

“…The microenvironments of CSCs are also considerable targets, since they provide suitable space for self-renewal and increased CSC chemical and radiological tolerance, which include vascularization, hypoxia, tumour-associated macrophages/fibroblasts, and the extracellular matrix [ 83 ]. The drug and gene delivery systems, such as nanoparticles, have also been extensively studied for enhancing targeting therapies for CSCs in paediatric CNS tumours [ 166 ]. In recent preliminary reports, controversial results were achieved for the same (class) medications in several common paediatric CNS tumours by different study groups.…”

Nanoparticle-Shielded dsRNA Delivery for Enhancing RNAi Efficiency in Cotton Spotted Bollworm Earias vittella (Lepidoptera: Nolidae)

“…Nanoparticles are particulate dispersions or solid particles with particle sizes in the range of 10-1000 nm. Nanocarriers can protect RNAi molecules from enzymatic degradation and immune recognition and have much higher transportation efficiency across the cell membrane than other carriers [20,21]. Various nanoparticles already in use for gene delivery in different insects include silica nanoparticles (SNs), layered double hydroxides (LDHs) nanoparticles, liposomes, solid lipid nanoparticles (SLNs), and polymer nanoparticles [22][23][24].…”