Multifunctional Poly(L-lactide)-Polyethylene Glycol-Grafted Graphene Quantum Dots for Intracellular MicroRNA Imaging and Combined Specific-Gene-Targeting Agents Delivery for Improved Therapeutics.
Photoluminescent (PL) graphene quantum dots (GQDs) with large surface area and superior mechanical flexibility exhibit fascinating optical and electronic properties and possess great promising applications in biomedical engineering. Here, a multifunctional nanocomposite of poly(l-lactide) (PLA) and polyethylene glycol (PEG)-grafted GQDs (f-GQDs) was proposed for simultaneous intracellular microRNAs (miRNAs) imaging analysis and combined gene delivery for enhanced therapeutic efficiency. The functionalization of GQDs with PEG and PLA imparts the nanocomposite with super physiological stability and stable photoluminescence over a broad pH range, which is vital for cell imaging. Cell experiments demonstrate the f-GQDs excellent biocompatibility, lower cytotoxicity, and protective properties. Using the HeLa cell as a model, we found the f-GQDs effectively delivered a miRNA probe for intracellular miRNA imaging analysis and regulation. Notably, the large surface of GQDs was capable of simultaneous adsorption of agents targeting miRNA-21 and survivin, respectively. The combined conjugation of miRNA-21-targeting and survivin-targeting agents induced better inhibition of cancer cell growth and more apoptosis of cancer cells, compared with conjugation of agents targeting miRNA-21 or survivin alone. These findings highlight the promise of the highly versatile multifunctional nanocomposite in biomedical application of intracellular molecules analysis and clinical gene therapeutics.
Haifeng
H
Dong
Wenhao
W
Dai
‡State Key Laboratory of Analytical Chemistry for Life Science, Department of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, P.R. China.
Huangxian
H
Ju
Huiting
H
Lu
Shiyan
S
Wang
Liping
L
Xu
⊥Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, Florida 33612, United States.
Shu-Feng
SF
Zhou
Yue
Y
Zhang
Xueji
X
Zhang
D002470:Cell Survival / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006108:Graphite / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008163:Luminescent Measurements / Q000379:methods; D035683:MicroRNAs / Q000032:analysis* / Q000235:genetics*; D057054:Molecular Imaging / Q000379:methods; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D045663:Quantum Dots; D000068936:Theranostic Nanomedicine / Q000379:methods; D014162:Transfection / Q000379:methods*
D035683:MicroRNAs; D053769:Nanocapsules; D011091:Polyesters; D011108:Polymers; C507889:polylactide-polyethylene glycol-polylactide; D011092:Polyethylene Glycols; D006108:Graphite
cell imaging; gene therapeutics; graphene quantum dots; microRNAs; survivin