Red Emitting, Cucurbituril-Capped, pH-Responsive Conjugated Oligomer-Based Nanoparticles for Drug Delivery and Cellular Imaging

Abstract

Here we report the synthesis of nanoparticles based on a conjugated oligomer which is synthesized through Heckcoupling of divinylfluorene and dibromobenzothiodiazole monomers. These water dispersible nanoparticles emit in the region of red tailing to the near-infrared region of the spectrum with high fluorescent quantum yield and brightness. The nanoparticles were found to be stable in water for a prolonged time without forming any aggregates and could carry camptothecin, an anticancer drug with high loading efficiency. MTT cell viability studies performed with breast cancer cell lines showed that halfmaximal inhibitory concentration (IC 50 ) values of nanoparticles for MCF7 and MDA-MB-231 were 44.7 μM and 24.8 μM, respectively. In order to further decrease the cytotoxicity and increase the stability of nanoparticles, amine groups were disguised by capping with cucurbit [7]uril (CB7). Drug release studies showed that drugs were released at low pH (at 5.0) faster than physiological pH (7.4) confirming the pH-responsive nature of the nanoparticles. On the other hand, CB7-capped drug-loaded nanoparticles regulated the release rate by providing slower release at pH 7.4 than the nanoparticles in the absence of CB7s. IC 50 values for camptothecin in the presence of nanoparticles with or without CB7 were significantly reduced in MCF7 and MDA-MB-231 cells. ■ INTRODUCTIONConjugated polymer nanoparticles (CPNs) are highly appealing for various advanced applications such as in vivo imaging, cell labeling, and delivery of therapeutic agents, as well as nanophotonics, owing to their high quantum yields and molar absorptivity, tunable properties, easy functionalization, photostability, and so forth. 1−7 To date, the use of CPNs has been demonstrated successfully in cell imaging, oxygen sensing, drug delivery, and nucleic acid delivery. 8−16 When these nanostructures are judiciously designed, they can be utilized in theranostic applications by combining more than one functionality to deliver therapeutic and imaging agents. 17−21 For the controlled delivery of therapeutic agents to the targets the nanoparticles could also include responsive groups that will respond to stimuli such as pH, oxidation−reduction, and enzymes. However, in the literature, examples are scarce regarding the multifunctional conjugated polymer nanoparticles (CPNs) and even less with conjugated oligomer-based nanoparticles (CONs). 22,23 Recently, Schenning et al. compared the capabilities of conjugated polymer nanoparticles to selfassembled oligomer-based nanoparticles in terms of their fluorescent quantum yields, stabilities, molar absorptivity, guest-holding, and releasing. 24 They demonstrated that oligomer nanoparticles have higher fluorescent quantum yields and comparable stabilities and molar absorptivity, but they release the guest faster than the conjugated polymer nanoparticles. Thus, this feature should be considered for the further design of oligomer-based nanoparticles for theranostic applications. CONs also offer some useful addi...

pH-responsive molecular assemblies of pyridylbutadiene derivative with cucurbit[7]uril

“…22,24,[47][48][49] To investigate the formation of such molecular assemblies, we examined the morphology of dye, CB7, and inclusion complex of the CB7-dye complex at different pH solutions using SEM, AFM, and optical microscopic techniques. Fig.…”

Supramolecular Assemblies of Cucurbiturils with Photoactive, π‐conjugated Chromophores

“…[44] For this purpose, poly[9, 9-bis{6(N,N-dimethylamino)hexyl}fluoreneco-2,5thienylene (PFT) was synthesized and its optical properties have been investigated in the presence and the absence of CB homologues. [45] Conjugated oligomer was synthesized through Heck coupling of divinylfluorene and dibromobenzothiodiazole monomers and has an amphiphilic nature due to the presence of tertiary alkyl amine residues as pendant of the fluorene monomer. This complex emits green and is highly fluorescent with fluorescence quantum yield of 35 %.…”

“…We have observed that this nonionic conjugated polymer can be made soluble in water through an inclusion complex formation with CB8. [45] Cationic conjugated polyelectrolytes can be used in photodynamic antibacterial chemotherapy in which cationic ammonium groups interact with the negatively charge bacterial cell membranes and the photoactive backbone of the polymers acts as a photosensitizer that can be irradiated by light to generate the reactive oxygen species for photodynamic effect. It was also observed that the morphology of the polymer PFT was affected by the presence of CB8.…”

Self-Assembled Fluorescent Nanoparticles from π-Conjugated Small Molecules: En Route to Biological Applications

“…Combining fluorescence imaging, encapsulation of hydrophobic guest molecules, and drug delivery, Tuncel et al reported on fluorene‐based nanoparticles which encapsulate a drug and emit fluorescence in the red region tailing to infrared (Figure ). The two fluorene units, both bearing two amine substituted side chains, are bridged by a central divinyl benzothiadiazole moiety, resulting in an oligomer bearing a hydrophobic backbone and hydrophilic side chains.…”