Research
Neurological disorders are diseases connected to the peripheral and central nervous system (CNS). They remain the primary cause of disability on a global scale, and their impact on the overall burden of health conditions is steadily growing. Our research focuses on investigating the impact of neurological disorders on the CNS microenvironment, in order to develop treatment strategies that can improve the quality of life for individuals affected by these conditions. Our approach involves the discovery and characterization of clinically relevant biomarkers and their application in disease early detection, the design of drug delivery systems that are responsive to the microenvironment, and the development of biomedical devices for disease modeling and precision therapy.
Nanoparticle for Biomedical Applications
Nanoscale Horiz., 2017,2, 187-198
Gold nanoparticles have gained significant attention in the field of biomedical applications due to their unique physical and chemical features. To understand the relationship between nanoparticles and their biological function, we developed a microfluidic setup that enables automatic nanoparticle synthesis. In particular, this setup allows the study of the growth evolution of complex shapes with a high spatial resolution, which facilitates the identification of key parameters for more precise control of the generated morphologies. We also studied how the physicochemical properties of the nanoparticles contribute to their bioactivity, such as pharmacokinetics, biodistribution, and shape-dependent immunological response both in vitro and in vivo.
Our current and future work is focusing on the development of functional nanoparticles for sensing, drug delivery, and biomedical imaging for CNS diseases.
Representative Publication
Q. Cai*, V. Castagnola*, L. Boselli*, A. Moura, H. Lopez, W. Zhang, J. M. de Araujo, K. A. Dawson. A microfluidic approach for synthesis and kinetic profiling of branched gold nanostructure. Nanoscale Horizons, 2022, 7, 288-298. (*co-first author)
L. Talamini*, M. B. Violatto*, Q. Cai*, M. P. Monopoli, K. Kantner, Ž. Krpetić, A. Perez-Potti, J. Cookman, D. Garry, C. P. Silveira, L. Boselli, B. Pelaz, T. Serchi, S. Cambier, A. C. Gutleb, N. Feliu, Y. Yan, M. Salmona, W. J. Parak, K. A. Dawson, Paolo Bigini. Influence of size and shape on the anatomical distribution of endotoxin-free gold nanoparticles. ACS Nano 2017, 11, 6, 5519–5529. (*co-first author)
Y. Liu, H. Ye, A. Bayram, T. Zhang, Q. Cai, C. Xie, H. Huynh, S. Peerzade, J. Kahn, Z. Qin. Gold Nanourchins improve virus targeting and plasmonic coupling for virus diagnosis on a smartphone platform. ACS Sensors., 2022, 7, 12, 3741–3752. cover article
Stimuli-Responsive Drug Delivery to the Central Nervous System
Nano Lett. 2021, 21, 22, 9805–9815
The blood-brain barrier (BBB) is highly selective and acts as the interface between the central nervous system and circulation. While the BBB is critical for maintaining brain homeostasis, it represents a formidable challenge for drug delivery. We developed an optical approach to modulate the BBB with picosecond-laser excitation of vascular-targeted plasmonic gold nanoparticles. We illustrated the mechanobiological pathways that contributed to the BBB opening. We further advanced this approach to modulate the blood-brain-tumor barrier and proposed a novel method for glioblastoma treatment in clinically relevant genetically engineered mouse models. This approach offers high efficacy, safety, and precision for brain drug delivery.
Our future work will be centered on investigating the disease microenvironment and developing microenvironment-responsive nanomaterials to enhance the specificity and efficacy of drug delivery, reduce off-target effects, and improve the overall therapeutic outcomes in CNS disease treatment.
Representative Publication
Q. Cai, X. Li, H. Xiong, H. Fan, X. Gao, V. Vemireddy, R. Margolis, J. Li, M. Giannotta, K. Hoyt, R. Bachoo, Z. Qin. Transcranial blood-brain-tumor barrier modulation for enhancing drug delivery to glioblastoma. Nature Communications, 2023, 14, 4934.
X. Li, Q. Cai*, M. Giannotta, H. Fan, E. Dejana, R. Bachoo, Z. Qin. Laser-induced calcium signaling for temporary blood-brain barrier opening. Nanoscale, 2023,15, 3387-3397 (*co-first author)
X. Li*, V. Vemireddy*, Q. Cai*, H. Xiong, P. Kang, X. Li, M. Giannotta, H. N. Hayenga. E. Pan, S. R. Sirsi, C. Mateo, D. Kleinfeld, C. Greene, M. Campbell, E. Dejana, R. Bachoo, Z. Qin. Reversibly modulating the blood-brain barrier by laser stimulation of molecular-targeted nanoparticles. Nano Letters, 2021, 21, 22, 9805–9815. (*co-first author) cover article
Human Organ-on-a-chip for Disease Modeling, Drug Discovery and Precision Medicine
Over the past decade, it has been recognized that no two patients' cancers are the same and may have variable responses to generic treatments such as chemotherapy and radiation. These traditional cancer therapies are overly simplified, resulting in ineffective, expensive treatments and causing patients to suffer unnecessary side effects.
To address this problem, we aim to develop 3D biomimetic platforms that better evaluate CNS diseases for precision therapy. Such platforms will facilitate the identification of effective therapeutic strategies and may help guide the choice of clinical trials for individual patients.
