Perylene-derived single-component organic nanoparticles with tunable emission: efficient anticancer drug carriers with real-time monitoring of drug release.
An organic nanoparticle-based drug delivery system with high drug loading efficacy (∼79 wt %) was developed using a perylene-derived photoremovable protecting group, namely, perylene-3,4,9,10-tetrayltetramethanol (Pe(OH)4). The anticancer drug chlorambucil was protected by coupling with Pe(OH)4 to form photocaged nanoparticles (Pe(Cbl)4). The photorelease mechanism of chlorambucil from the Pe(Cbl)4 conjugate was investigated experimentally by high-resolution mass spectrometry and theoretically by density functional theory calculations. The Pe(Cbl)4 nanoparticles perform four important roles: (i) a nanocarrier for drug delivery, (ii) a phototrigger for drug release, (iii) a fluorescent chromophore for cell imaging, and (iv) a photoswitchable fluorophore for real-time monitoring of drug release. Tunable emission of the perylene-derived nanoparticles was demonstrated by comparing the emission properties of the Pe(OH)4 and Pe(Cbl)4 nanoparticles with perylene-3-ylmethanol. These nanoparticles were subsequently employed in cell imaging for investigating their intracellular localization. Furthermore, the in vivo toxicity of the Pe(OH)4 nanoparticles was investigated using the mouse model. Histological tissue analysis of five major organs, i.e., heart, kidney, spleen, liver, and lung, indicates that the nanoparticles did not show any obvious damage to these major organs under the experimental conditions. The current research presents a successful example of integrating multiple functions into single-component organic nanoparticles for drug delivery.
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University , 21 Nanyang Link, Singapore 637371.
Avijit
A
Jana
Kim Truc
KT
Nguyen
Xin
X
Li
Pengcheng
P
Zhu
Nguan Soon
NS
Tan
Hans
H
Ågren
Yanli
Y
Zhao
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D002699:Chlorambucil / Q000737:chemistry; D004337:Drug Carriers; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D009930:Organic Chemicals / Q000737:chemistry*; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry*; D010777:Photochemistry; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D004337:Drug Carriers; D009930:Organic Chemicals; C000602569:perylene-3,4,9,10-tetrayltetramethanol; D002699:Chlorambucil; D010569:Perylene