Overcoming Biological Barriers: A Review of Nanomedicine Strategies for Crossing the Blood-brain Barrier in Neuro-oncology View PDF

BBB serves as a critical protective mechanism for the central nervous system (CNS), selectively allowing the passage of essential nutrients while blocking harmful substances [1-5]. The challenge of crossing the BBB remains a significant obstacle in the effective treatment of neuro-oncological conditions, prompting extensive research into nanomedicine strategies designed to overcome this biological barrier [6-10]. The BBB’s restrictive nature, which protects the brain from circulating harmful agents, also impedes therapeutic agents, including chemotherapeutics and immunomodulators, from reaching intracranial targets [11]. Consequently, innovative nanotechnologybased approaches are being developed to facilitate drug delivery across this barrier. One prominent strategy involves exploiting BBB receptors and transporters to enhance nanoparticle translocation. Moura et al. [11] highlight the importance of understanding the structure and function of these receptors to develop targeted nanocarriers that can engage specific transport mechanisms. Similarly, Pinheiro et al. [12] emphasize the necessity of designing nanoparticles capable of BBB passage to reach targeted brain regions effectively. These receptormediated approaches are central to improving nanomedicine delivery efficiency in neuro-oncology.

Physicochemical properties of nanocarriers significantly influence their ability to traverse biological barriers, including the BBB [13-17]. Wang et al. [18] discuss how parameters such as particle size, surface charge, morphology, and surface modifications can be tailored to optimize barrier penetration. For instance, surface modifications can enhance nanoparticle stability and facilitate receptor engagement, thereby improving brain uptake. Such insights are critical for designing nanomedicines capable of crossing the BBB in neuro-oncological applications. In addition to receptor targeting and physicochemical optimization, various nanoparticle platforms have been explored. Cunha et al. [19] review the use of poly(lactic-co-glycolic acid) (PLGA)- based nanoparticles for neuroprotective drug delivery, demonstrating their potential to bypass biological barriers and deliver therapeutic agents effectively. Similarly, Khilar et al. [20] provide a comprehensive overview of nanomedicine strategies, including chemotherapy, immunotherapy, and advanced techniques like focused ultrasound, to facilitate BBB crossing in brain tumor treatment. These approaches underscore the multifaceted nature of nanomedicine strategies aimed at overcoming the BBB.

Gold nanoparticles have garnered particular interest due to their unique properties. Tarantino et al. [21] discuss the role of gold nanoparticles as therapeutic enhancers in brain cancer treatment, emphasizing their capacity to improve drug delivery and therapeutic efficacy across the BBB. Their ability to be functionalized with targeting ligands makes them promising candidates for neurooncological applications. Furthermore, the review by Khilar et al. [20] underscores the ongoing development of nanomedicine protocols that integrate various modalities such as chemotherapy, immunotherapy, and radiotherapy, often employing nanocarriers to facilitate BBB penetration. These integrated strategies aim to enhance therapeutic outcomes by ensuring adequate drug concentrations within brain tumors.

In summary, current nanomedicine strategies for crossing the BBB in neuro-oncology focus on receptor-mediated targeting, physicochemical optimization of nanocarriers, and multifunctional nanoparticle platforms. These approaches are supported by a growing understanding of BBB biology and nanocarrier design principles, offering promising avenues for improving treatment efficacy in brain tumors.