TY - JOUR
T1 - Nontoxic amphiphilic carbon dots as promising drug nanocarriers across the blood-brain barrier and inhibitors of β-amyloid
AU - Zhou, Yiqun
AU - Liyanage, Piumi Y.
AU - Devadoss, Dinesh
AU - Rios Guevara, Linda Rebeca
AU - Cheng, Ling
AU - Graham, Regina M.
AU - Chand, Hitendra S.
AU - Al-Youbi, Abdulrahman O.
AU - Bashammakh, Abdulaziz S.
AU - El-Shahawi, Mohammad S.
AU - Leblanc, Roger M.
N1 - Funding Information:
This work was supported by National Science Foundation under the grant 011298. Also, authors gratefully acknowledge the great support from King Abdulaziz University, Kingdom of Saudi Arabia, and University of Miami, USA. Prof. Hitendra S. Chand acknowledges support from NIH grants R01DA040537 and R03DA044877, the Florida International University, Herbert Wertheim College of Medicine, and Office of Research and Economic Development Startup funds.
Funding Information:
Wild-type zebrafish at 5 days after fertilization were obtained from the Zebrafish Core Facility at University of Miami. 0.1 mg mL−1 Y-CDs aqueous dispersion was injected into the heart of zebrafish previously anesthetized by tricaine. After 10 min, the injected zebrafish were subjected for observation under a Leica SP5 confocal microscope under white light and excitation at 405 nm (for Y-CDs). The animal care protocol for all procedures used in this study was approved by the University of Miami Animal Care and Use Committee and complies with the guidelines of the National Science Foundation.
Publisher Copyright:
© The Royal Society of Chemistry 2019.
PY - 2019/12/14
Y1 - 2019/12/14
N2 - The blood-brain barrier (BBB) is a main obstacle for drug delivery targeting the central nervous system (CNS) and treating Alzheimer's disease (AD). In order to enhance the efficiency of drug delivery without harming the BBB integrity, nanoparticle-mediated drug delivery has become a popular therapeutic strategy. Carbon dots (CDs) are one of the most promising and novel nanocarriers. In this study, amphiphilic yellow-emissive CDs (Y-CDs) were synthesized with an ultrasonication-mediated methodology using citric acid and o-phenylenediamine with a size of 3 nm that emit an excitation-independent yellow photoluminescence (PL). The content of primary amine and carboxyl groups on CDs was measured as 6.12 × 10-5 and 8.13 × 10-3 mmol mg-1, respectively, indicating the potential for small-molecule drug loading through bioconjugation. Confocal image analyses revealed that Y-CDs crossed the BBB of 5-day old wild-type zebrafish, most probably by passive diffusion due to the amphiphilicity of Y-CDs. And the amphiphilicity and BBB penetration ability didn't change when Y-CDs were coated with different hydrophilic molecules. Furthermore, Y-CDs were observed to enter cells to inhibit the overexpression of human amyloid precursor protein (APP) and β-amyloid (Aβ) which is a major factor responsible for AD pathology. Therefore, data suggest that Y-CDs have a great potential as nontoxic nanocarriers for drug delivery towards the CNS as well as a promising inhibiting agent of Aβ-related pathology of the AD.
AB - The blood-brain barrier (BBB) is a main obstacle for drug delivery targeting the central nervous system (CNS) and treating Alzheimer's disease (AD). In order to enhance the efficiency of drug delivery without harming the BBB integrity, nanoparticle-mediated drug delivery has become a popular therapeutic strategy. Carbon dots (CDs) are one of the most promising and novel nanocarriers. In this study, amphiphilic yellow-emissive CDs (Y-CDs) were synthesized with an ultrasonication-mediated methodology using citric acid and o-phenylenediamine with a size of 3 nm that emit an excitation-independent yellow photoluminescence (PL). The content of primary amine and carboxyl groups on CDs was measured as 6.12 × 10-5 and 8.13 × 10-3 mmol mg-1, respectively, indicating the potential for small-molecule drug loading through bioconjugation. Confocal image analyses revealed that Y-CDs crossed the BBB of 5-day old wild-type zebrafish, most probably by passive diffusion due to the amphiphilicity of Y-CDs. And the amphiphilicity and BBB penetration ability didn't change when Y-CDs were coated with different hydrophilic molecules. Furthermore, Y-CDs were observed to enter cells to inhibit the overexpression of human amyloid precursor protein (APP) and β-amyloid (Aβ) which is a major factor responsible for AD pathology. Therefore, data suggest that Y-CDs have a great potential as nontoxic nanocarriers for drug delivery towards the CNS as well as a promising inhibiting agent of Aβ-related pathology of the AD.
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U2 - 10.1039/c9nr08194a
DO - 10.1039/c9nr08194a
M3 - Article
C2 - 31730144
AN - SCOPUS:85075812533
VL - 11
SP - 22387
EP - 22397
JO - Nanoscale
JF - Nanoscale
SN - 2040-3364
IS - 46
ER -