Perylene-Derived Single-Component Organic Nanoparticles with Tunable Emission: Efficient Anticancer Drug Carriers with Real-Time Monitoring of Drug Release

Abstract

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.

Chronic Kidney Diseases and Nanoparticle Therapeutics

“…These Pe(OH)4 nanoparticles do not show toxic effect on major organs under the experimental conditions [76]. Mn-NPs are also used for delivery of drugs to the target organ [77].…”

Photoactivation of Butyric Acid from 6‐Aminobenzocoumarin Cages

“…upon irradiation, [4] ii) photoactive polymers for encapsulation of guest molecules and as drug delivery systems, [5,6] iii) photoactive nanoparticle carriers for therapeutic agent release, iv) targeted cancer therapies, in nanomedicine and diagnostics, [7][8][9][10] v) photoactive hydrogels with tunable mechanical properties as scaffolds for cell culture and tissue regeneration, [11,12] vi) light controlled antibacterial agents for selecting specific bacterial strains from microbial mixtures for healthcare and microbiology research, [13] vii) agents enabling photocontrolled synthesis of aptamer-drug conjugates for selective tissue recognition in targeted cancer therapy, [14] viii) photolabile linkers for solid phase synthesis of peptides and heterocycles, [15,16] and ix) agents to enable the uncaging of bioactive molecules such as antibiotics, oligonucleotides and neurotransmitters from photolabile precursors.…”

Nanoscaled rhodamine dyes with 4.5-fold longer fluorescence lifetimes and 150 nm red shifted fluorescence spectra: Preparation, size tuning and optical properties

“…The studies on fluorescent pure organic nanoparticles have been focusing on perylene [12,13], carbazoles [14,15], and cyanine dyes [16,17]. Nanoscaled rhodamine dyes have not been explored in depth on the preparation and properties except for a recent report in which UV-induced formation of rhodamine B nanoparticles was found [18].…”