Nanomaterials for brain metastasis
Time：2023/12/18 14:14:36 Views：143
Tumor metastasis is a significant contributor to the mortality of cancer patients. Specifically, current conventional treatments are unable to achieve complete remission of brain metastasis. This is due to the unique pathological environment of brain metastasis, which differs significantly from peripheral metastasis. Brain metastasis is characterized by high tumor mutation rates and a complex microenvironment with immunosuppression. Additionally, the presence of blood-brain barrier (BBB)/blood tumor barrier (BTB) restricts drug leakage into the brain. Therefore, it is crucial to take account of the specific characteristics of brain metastasis when developing new therapeutic strategies. Nanomaterials offer promising opportunities for targeted therapies in treating brain metastasis. They can be tailored and customized based on specific pathological features and incorporate various treatment approaches, which makes them advantageous in advancing therapeutic strategies for brain metastasis. This review provides an overview of current clinical treatment options for patients with brain metastasis. It also explores the roles and changes that different cells within the complex microenvironment play during tumor spread. Furthermore, it highlights the use of nanomaterials in current brain treatment approaches. The related results, titled nanomaterials for brain metastasis, were published online in the Journal of Controlled Release, an internationally renowned journal.
A biologically inefficient process, tumor metastasis occurs when tumor cells spread and adapt to the specific microenvironments at different metastatic sites. Unfortunately, 90% of cancer-related deaths are attributed to metastasis. Most malignant tumor metastases to the brain have the worst outlook as they represent a significant burden. Despite the tight regulation and protection provided by the blood-brain barrier (BBB), brain metastasis (BM) still occurs in 10-40% of cancer patients, making them more than four times as common as primary brain tumors. Unlike primary brain tumors, brain metastases arise from the colonization of peripheral primary tumors in the brain, possess a more complex microenvironment, and lack definitive treatment. The current treatment strategy for BM involves multimodality approaches such as surgery, radiotherapy, and drug therapy. Current treatments, however, have not exhibited benefits, leaving patients with BM with low survival rates after two years. This can be attributed to the fact that current therapeutic approaches do not adequately take into account the unique characteristics of brain metastasis. These include highly heterogeneous features of metastatic cellular pathology, complex microenvironment at metastatic sites, and challenges posed by the BBB/blood tumor barrier (BTB). With improving survival rates following cancer diagnosis and advancements in neuroimaging techniques like MRI, the reported and actual incidence of BM may rise. Therefore, it is an urgent to develop targeted therapeutic approaches based on the pathological characteristics of brain metastasis.
It is possible for all primary tumors to metastasize to the brain. However, lung cancer (20-56% of patients with lung cancer develop brain metastasis; 40-50% of all patients with brain metastasis), breast cancer (18-30%; 15-30%), and melanoma (10-73%; 5-20%) are the most common types. Generally, metastatic cells spread through the blood from the primary tumor to the cerebral microvasculature via hematogenous mechanisms, but seeding from established metastasis is also possible. Several factors contribute to the establishment of new metastasis and may be potential contributors to poor prognosis, including microenvironment-tumor interactions, potential neovascularization, and neuroinflammatory cascades. With the exploration of the role of different cell types in the brain metastasis, the significance of various cell types in brain metastasis has gained recognition, including intrinsic cells, myeloid cells, and tumor-infiltrating lymphocytes (TIL), all playing a role in tumor colonization within the brain. This understanding provides valuable insights for BM treatment. Translating these discoveries into new therapies and integrating them with means to increase BBB penetration will be key advances necessary for improving outcomes for patients with BM. Nanomedicines have the potential to accelerate this idea's realization and represent a promising therapeutic strategy for BMs. The use of nanomaterials (NMs) for delivering drugs directly to the brain has significant advantages. NMs can be specifically designed and modified to match the unique physiological properties of the brain, making them highly effective in penetrating the blood-brain barrier (BBB) and targeting specific cells. They also have the capability to load or encapsulate various therapeutic drugs, enhancing stability while limiting side effects. Additionally, they can be tailored for specific or controlled drug release. In this manuscript, we provide a comprehensive review on managing patients with BM, focusing on understanding how different cell types in BM contribute to tumor growth or suppression. We highlight the potential of nanomaterials in enhancing existing therapies and discuss ongoing research efforts in intracerebral drug delivery for BM treatment.
Different nanomaterials for brain metastasis.
Doctoral student Zhao Zhenhao in our group is the first authors of the paper, and Professor Jiang Chen is the corresponding author of the paper. The research was supported by the National Natural Science Foundation of China, the Shanghai Academic Research Leaders Program and other projects.
links：https://www.sciencedirect.com/science/article/pii/S016836592300785X?dgcid=coauthor
