Smart Nanoformulations for Brain Cancer Theranostics: Challenges and Promises

Abstract

Despite their low prevalence, brain tumors are among the most lethal cancers. They are extremely difficult to diagnose, monitor and treat. Conventional anti-cancer strategies such as radio- and chemotherapy have largely failed, and to date, the development of even a single effective therapeutic strategy against central nervous system (CNS) tumors has remained elusive. There are several factors responsible for this. Brain cancers are a heterogeneous group of diseases with variable origins, biochemical properties and degrees of invasiveness. High-grade gliomas are amongst the most metastatic and invasive cancers, which is another reason for therapeutic failure in their case. Moreover, crossing the blood brain and the blood brain tumor barriers has been a significant hindrance in the development of efficient CNS therapeutics. Cancer nanomedicine, which encompasses the application of nanotechnology for diagnosis, monitoring and therapy of cancers, is a rapidly evolving field of translational medicine. Nanoformulations, because of their extreme versatility and manipulative potential, are emerging candidates for tumor targeting, penetration and treatment in the brain. Moreover, suitable nanocarriers can be commissioned for theranostics, a combinatorial personalized approach for simultaneous imaging and therapy. This review first details the recent advances in novel bioengineering techniques that provide promising avenues for circumventing the hurdles of delivering the diagnostic/therapeutic agent to the CNS. The authors then describe in detail the tremendous potential of utilizing nanotechnology, particularly nano-theranostics for brain cancer imaging and therapy, and outline the different categories of recently developed next-generation smart nanoformulations that have exceptional potential for making a breakthrough in clinical neuro-oncology therapeutics.

Molecular mechanisms of neuroprotective offerings by rosmarinic acid against neurodegenerative and other CNS pathologies

“…Indeed, several nanoformulation strategies have been and continue to be evaluated for this purpose (Baranauskaite et al, 2018; Fachel et al, 2019; Madureira et al, 2016). For increasing the bioavailability of RA and its efficient transformation into a viable phytochemical therapeutic agent, research groups should exploit the vast nanotechnlogical avenues for enhancing its targeted brain delivery and bioavailability (Ahmad et al, 2022; Guan et al, 2022). In this regard, nasal route of targeted brain delivery across the BBB is fast emerging as an efficacious method for evaluating and applying the therapeutic prospect of RA‐based nanoplatforms in CNS disorders.…”

“…These include topical application, for example against skin ageing (Marafon et al, 2019; Yücel et al, 2019), and pulmonary administration (Lu et al, 2019). The nose‐to‐brain delivery of functionalized smart nanoformulations through the olfactory bulb may in fact be an extremely effective route of bypassing the blood brain barrier (BBB) for the nanoformulations loaded with exogenous chemicals (Ahmad et al, 2022; Wang et al, 2019), such as RA. For example, the intranasal route of administration of a RA‐based solid lipid nanoformulation has been explored for neuroprotection in a chemically (3‐nitro propionic acid; 3‐NP)‐induced model of Huntington's disease (HD; Section 4.5.4), with encouraging results, eliciting reduced oxidative damage and motor deficits (Bhatt et al, 2015).…”

Progress and Challenges in the Diagnosis and Treatment of Brain Cancer Using Nanotechnology

“…Metallic nanoparticles produce reactive oxygen species that last for a very long time and have unknown effects. 75 After crossing the BBB, gold nanoparticles may result in three types of severe neurological pathologies, which include (1) increased seizure activity, (2) increased astrogliosis, also known as reactive astrocytosis, which is characterized by an increased number of astrocytes brought on by the death of nearby neurons and inhibits axon regeneration, and (3) cognitive impairments such as memory loss and attention defects. 220 Titanium oxide nanoparticles cause neurotoxicity primarily by oxidative stress, inflammatory reactions, apoptosis, genotoxicity, and cell component damage.…”

“…To assess the biological activity, including the toxicity, of nanoparticles, new nanocompatible assays are being developed. Researchers can minimize the risks before beginning a clinical trial by carefully defining the inclusion and exclusion criteria for participants who are likely to be affected by the study, closely observing the outcomes during and after the trials, reporting to the authorities and review board, and carrying out a comprehensive literature review on their topic of interest to learn about potential side effects . The pharmacokinetics of nanomedicines should be researched, and in vitro and in vivo investigations should be carried out to determine their absorption, distribution, metabolism, and excretion to reduce the risk of harmful effects.…”

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

“…Another interesting aspect is the application of NPs as a diagnostic tool. Indeed, NPs can be used as theranostic agents, in a synergistic manner, to deliver therapeutic and imaging agents together [ 28 , 29 ]. Therapeutic strategies based on NPs would benefit from their intrinsic ability to access the niche where the CSCs reside and successfully act on the crosstalk between the tumor and microenvironment, as well as target the unique phenotypes and functional properties of CSCs.…”