Breaking the barrier: Nanoparticle-enhanced radiotherapy as the new vanguard in brain tumor treatment

Abstract

The pursuit of effective treatments for brain tumors has increasingly focused on the promising area of nanoparticle-enhanced radiotherapy (NERT). This review elucidates the context and significance of NERT, with a particular emphasis on its application in brain tumor therapy-a field where traditional treatments often encounter obstacles due to the blood-brain barrier (BBB) and tumor cells' inherent resistance. The aims of this review include synthesizing recent advancements, analyzing action mechanisms, and assessing the clinical potential and challenges associated with nanoparticle (NP) use in radiotherapy enhancement. Preliminary preclinical studies have established a foundation for NERT, demonstrating that nanoparticles (NPs) can serve as radiosensitizers, thereby intensifying radiotherapy's efficacy. Investigations into various NP types, such as metallic, magnetic, and polymeric, have each unveiled distinct interactions with ionizing radiation, leading to an augmented destruction of tumor cells. These interactions, encompassing physical dose enhancement and biological and chemical radio sensitization, are crucial to the NERT strategy. Although clinical studies are in their early phases, initial trials have shown promising results in terms of tumor response rates and survival, albeit with mindful consideration of toxicity profiles. This review examines pivotal studies affirming NERT's efficacy and safety. NPs have the potential to revolutionize radiotherapy by overcoming challenges in targeted delivery, reducing off-target effects, and harmonizing with other modalities. Future directions include refining NP formulations, personalizing therapies, and navigating regulatory pathways. NERT holds promise to transform brain tumor treatment and provide hope for patients.

Keywords: blood-brain barrier; brain tumor; clinical translation; nanoparticle-enhanced radiotherapy; radio sensitization; regulatory landscapes.

FIGURE 1

Schematic representation of the multifaceted synergistic effects of nanocarrier-enhanced radiotherapy for brain tumors. The illustration depicts the key mechanisms by which nanocarriers can enhance the efficacy of radiotherapy, including targeted delivery, radiosensitization, and the ability to overcome the blood-brain barrier.

FIGURE 2

Schematic illustration of the potential of gold nanoparticles (AuNPs) as innovative radiosensitizers. The figure highlights the effective X-ray absorption, versatile synthesis, and distinctive chemical and optical properties of AuNPs. The interdisciplinary research efforts aimed at uncovering the mechanisms behind the enhanced radiation effects of AuNPs are also represented.

FIGURE 3

Formulation and in vivo biodistribution of targeted albumin nanoparticles. Schematic representation of the formulation process, including crosslinking, loading of STAT3 inhibitors, and iRGD conjugation. Adapted from Gregory et al., 2020.

FIGURE 4

Schematic representation of the primary cell death mechanisms triggered by radiation. The figure illustrates that radiation-induced cell death occurs mainly through apoptosis or mitotic catastrophe. Apoptosis is characterized by the activation of caspases, leading to the formation of apoptotic bodies, while mitotic catastrophe results from aberrant mitosis and the formation of giant cells with multiple nuclei. Adapted from Baskar et al., 2012.

FIGURE 5

Schematic illustration of the size-dependent membrane-wrapping behavior of nanoparticles (NPs). The figure shows that NPs with diameters above 60 nm drive the membrane-wrapping process by binding extensively to receptors, while NPs below 30 nm attach to the membrane but require proximity for efficacy. NPs with diameters between 30 and 60 nm effectively drive membrane-wrapping. Redrawn based on the content of Hoshyar et al., 2016.