Multimodal neuro- nanotechnology: Challenging the existing paradigm in glioblastoma therapy

• 成果类型: Article
• 署名作者: Kudruk, Sergej; Forsyth, Connor M.; Dion, Michelle Z.; Orbeck, Jenny K. Hedlund; Luo, Jingqin; Klein, Robyn S.; Kim, Albert H.; Heimberger, Amy B.; Mirkin, Chad A.; Stegh, Alexander H.; Artzi, Natalie
• 署名单位: Northwestern University; Northwestern University; Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Siteman Cancer Center; Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); Robert H. Lurie Comprehensive Cancer Center; Ann & Robert H. Lurie Children's Hospital of Chicago; Northwestern University; Feinberg School of Medicine; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10288
• DOI: 10.1073/pnas.2306973121
• 发表日期: 2024-02-20
• 关键词: blood-brain-barrier; interstitial thermal therapy; drug-delivery; gold nanoparticles; focused ultrasound; signal transducer; intracellular dna; transcription 3; t-cells; glioma

摘要

Integrating multimodal neuro- and nanotechnologyenabled precision immunotherapies with extant systemic immunotherapies may finally provide a significant breakthrough for combatting glioblastoma (GBM). The potency of this approach lies in its ability to train the immune system to efficiently identify and eradicate cancer cells, thereby creating anti- tumor immune memory while minimizing multi- mechanistic immune suppression. A critical aspect of these therapies is the controlled, spatiotemporal delivery of structurally defined nanotherapeutics into the GBM tumor microenvironment (TME). Architectures such as spherical nucleic acids or poly(beta- amino ester)/dendrimer- based nanoparticles have shown promising results in preclinical models due to their multivalency and abilities to activate antigen- presenting cells and prime antigen- specific T cells. These nanostructures also permit systematic variation to optimize their distribution, TME accumulation, cellular uptake, and overall immunostimulatory effects. Delving deeper into the relationships between nanotherapeutic structures and their performance will accelerate nanodrug development and pave the way for the rapid clinical translation of advanced nanomedicines. In addition, the efficacy of nanotechnology- based immunotherapies may be enhanced when integrated with emerging precision surgical techniques, such as laser interstitial thermal therapy, and when combined with systemic immunotherapies, particularly inhibitors of immune- mediated checkpoints and immunosuppressive adenosine signaling. In this perspective, we highlight the potential of emerging treatment modalities, combining advances in biomedical engineering and neurotechnology development with existing immunoaccelerate their translation into the clinic.