Cancer persists as a major global health challenge, accounting for nearly 11 million newly diagnosed cases each year worldwide [1], [2], [3], [4], [5], [6]. Over 200 distinct types of cancer have been classified based on their tissue of origin and histological characteristics. Tumor development is driven primarily by alterations in two categories of genes: oncogenes and tumor suppressor genes. Proto-oncogenes, when subjected to mutations, chromosomal rearrangements, or gene amplifications, transform into oncogenes, which trigger unregulated cellular growth and division. These genetic alterations play a central role in the malignant transformation of normal cells, ultimately resulting in tumor formation and progression [7], [8], [9], [10], [11], [12], [13], [14], [15]. Under normal conditions, cell growth and division are tightly regulated by genes that promote cell proliferation, suppress excessive growth, or induce programmed cell death (apoptosis). However, cancer cells harbor mutations that allow them to evade these regulatory signals, enabling unchecked growth [16], [17], [18], [19], [20], [21], [22], [23].

Brain and central nervous system (CNS) tumors significantly contribute to cancer-related morbidity and mortality, affecting approximately 308,162 individuals globally and causing 251,329 deaths annually [24]. Brain tumors, including glioblastoma, arise from complex genetic and molecular alterations, with oncogenes playing a pivotal role in their initiation and progression. Among these, the epidermal growth factor receptor (EGFR) is frequently amplified in glioblastoma, particularly the mutant variant EGFRvIII, which promotes aggressive tumor behavior and resistance to therapy [25]. Similarly, mutations in the TP53 tumor suppressor gene disrupt apoptosis and genomic stability, enabling tumor growth [26]. Isocitrate dehydrogenase (IDH1/IDH2) mutations, while associated with lower-grade gliomas, lead to the production of the oncometabolite 2-hydroxyglutarate, fostering tumorigenesis [27]. Dysregulation of the PI3K/AKT/mTOR pathway further exacerbates tumor proliferation and survival, underscoring the multifaceted nature of molecular drivers in brain cancer [28]. These genetic abnormalities not only drive tumor growth but also complicate treatment due to the tumor's ability to adapt and evade therapeutic interventions. Conventional strategies for brain tumor treatment, including surgical resection, radiotherapy, and chemotherapy, often fail to achieve complete tumor eradication, particularly in aggressive types like glioblastoma. These methods are limited by low specificity and high rates of recurrence. Traditional drug delivery systems—such as capsules, tablets, and injections—face several challenges. These include poor solubility, limited bioavailability, short circulation times, and large particle sizes, all of which reduce their therapeutic potential. Most critically, the blood-brain barrier (BBB) and brain-tumor barrier significantly hinder the effective delivery of chemotherapeutic agents, limiting their ability to reach the brain in sufficient concentrations to combat tumor growth effectively [1], [29], [30], [31], [32], [33], [34].

Chemotherapy, a cornerstone of cancer treatment, employs cytotoxic drugs to disrupt DNA synthesis and inhibit cell division, targeting rapidly proliferating cells. However, these drugs lack selectivity, often causing damage to healthy cells, leading to side effects such as nausea, fatigue, hair loss, and immunosuppression. To improve outcomes, targeted cancer therapies have emerged, focusing on specific molecular pathways or proteins involved in tumor growth. These therapies aim to block growth signals, induce apoptosis in cancer cells, or activate the immune system to fight tumors. Additionally, targeted delivery of chemotherapeutic agents minimizes damage to healthy tissues and reduces systemic toxicity, thereby improving patient survival rates and quality of life. Despite their potential, targeted therapies face significant challenges. Effective implementation requires identifying the right molecular targets, designing suitable therapeutic agents, and ensuring efficient drug delivery to the affected site. Nanocarriers—engineered colloidal systems operating at the nanoscale—offer a promising solution to these challenges. These advanced systems enhance drug solubility, stabilize drugs against degradation, improve pharmacokinetics, reduce renal clearance, and extend circulation time. Furthermore, nanocarriers facilitate controlled drug release and improve the efficacy of poorly soluble anticancer agents, reducing toxicity without necessitating higher doses [35], [36], [37], [38], [39]. Nanotechnology has revolutionized cancer therapy by introducing advanced nanoparticle-based drug carriers such as liposomes, micelles, dendrimers, gold nanoparticles, and carbon nanotubes. For example, Doxil® (PEGylated liposomal doxorubicin), has shown improved pharmacokinetics and reduced cardiotoxicity in breast and ovarian cancers, and temozolomide-loaded nanoparticles, which are being actively investigated for enhancing blood–brain barrier penetration and drug delivery in glioblastoma treatment. These systems provide enhanced solubility, improved bioavailability, prolonged stability, and reduced toxicity, establishing them as excellent platforms for targeted treatment strategies [40], [41], [42], [43], [44], [45], [46], [47], [48], [49].

In the context of brain tumors, the advent of advanced nanocarriers has also enabled researchers to overcome the challenges posed by the BBB and BTB. Surface modifications and functionalization with targeting ligands allow these nanoparticles to cross the BBB and specifically accumulate in tumor tissues. Liposomes, for example, can encapsulate both hydrophilic and hydrophobic drugs and be engineered for active targeting of glioma cells. Similarly, responsive nanocarriers can release drugs in response to specific tumor microenvironmental triggers, such as changes in pH or oxidative stress [50], [51].

In conclusion, while traditional treatments for brain tumors remain critical, their limitations necessitate innovative approaches. Nanotechnology, with its ability to enhance the precision and efficacy of drug delivery, represents a transformative advancement in cancer therapy. By leveraging nanocarriers like liposomes and functionalized nanoparticles, the field is poised to overcome longstanding challenges, bringing hope for more effective and less toxic treatment modalities for brain cancer patients.