Carbon Dots: A Future Blood–Brain Barrier Penetrating Nanomedicine and Drug Nanocarrier

Abstract

Drug delivery across the blood–brain barrier (BBB) is one of the biggest challenges in modern medicine due to the BBB’s highly semipermeable property that limits most therapeutic agents of brain diseases to enter the central nervous system (CNS). In recent years, nanoparticles, especially carbon dots (CDs), exhibit many unprecedented applications for drug delivery. Several types of CDs and CD-ligand conjugates have been reported successfully penetrating the BBB, which shows a promising progress in the application of CD-based drug delivery system (DDS) for the treatment of CNS diseases. In this review, our discussion of CDs includes their classification, preparations, structures, properties, and applications for the treatment of neurodegenerative diseases, especially Alzheimer’s disease (AD) and brain tumor. Moreover, abundant functional groups on the surface, especially amine and carboxyl groups, allow CDs to conjugate with diverse drugs as versatile drug nanocarriers. In addition, structure of the BBB is briefly described, and mechanisms for transporting various molecules across the BBB and other biological barriers are elucidated. Most importantly, recent developments in drug delivery with CDs as BBB-penetrating nanodrugs and drug nanocarriers to target CNS diseases especially Alzheimer’s disease and brain tumor are summarized. Eventually, future prospects of the CD-based DDS are discussed in combination with the development of artificial intelligence and nanorobots.

Applications of Various Types of Nanomaterials for the Treatment of Neurological Disorders

“…According to the Global Burden of Disease studies and the World Health Organization, neurological disorders cause approximately 276 million disabilities with 9 million mortalities throughout the globe each year [9,193]. At the same time, these cases are expected to increase tremendously.…”

“…These nanoparticles include FeONPs, AgNPs, Gadolinium metallofullerene NPs, Ultrasmall gadolinium oxide NPs, Ce 2 O 3 NPs, ZnONPs, AuNPs, and PtNPs. Metallic nanoparticles are also used for the imaging of CNS [9,32].…”

“…Photothermal and photodynamic therapies are considered alternative approaches and are used to treat various NDs due to their ability to bypass the BBB. However, these therapies have side effects, including damage to tissues (especially skin tissues) and photosensitization [9,10]. Therefore, there is an urgent need for the development of potential therapeutic agents that can cross the BBB with no side effects to combat these diseases.…”

Carbon Dots in Bioimaging, Biosensing and Therapeutics: A Comprehensive Review

“…[183][184][185] Most of the CDs@drug complexes have cleavable chemical bonds, allowing the targeted release of drugs under the acidic environment of tumor sites or in response to other stimuli. [186][187][188] In addition to enhancing the delivery and controlled release at the target site, CDs can help overcome the drug resistance of cancer cells or other diseased cells.…”

Carbon Dots: An Innovative Tool for Drug Delivery in Brain Tumors

“…Besides this, their localization can be easily detected thanks to their brilliant fluorescence, paving the way to theranostic applications. Several in vitro and in vivo studies regarding the ability of C-dots and their conjugates to overcome the BBB have been reported in the literature (Table 2), garnering much interest from the scientific community [142][143][144]. Lu et al [145] synthesized nitrogen-doped C-dots (C-dot/PEI) using a one-pot hydrothermal treatment with citric acid in the presence of Polyethyleneimine (PEI), obtaining particles with an average size of ~2.6 nm and strong blue luminescence.…”