Self‐Assembled Squalene‐based Fluorescent Heteronanoparticles

Abstract

The preparation of fluorescent nanoparticles containing squalenoyl-paclitaxel and a squalene-based fluorescein derivative is presented. The formation of self-assembled heteronanoparticles was confirmed by using the quasielastic light scattering (QELS) technique. The internalization in A549 human lung carcinoma cells was verified by microscopy analysis. Finally, paclitaxel in nanoassemblies maintains its ability to target microtubules.The recent advances in nanotechnology and nanomaterials have been integrated into analytical chemistry for the design of large numbers of fluorescent chemical and biological probes. In recent years instead of using single organic dye probes, these organic fluorophores were encapsulated in a particle matrix. These particles are much brighter than the dyes alone because one particle contains several dyes molecules. In addition, these dyes are more photostable because the entrapment enhances the stability and biocompatibility of the fluorophores. The small size of the nanoparticles allows a high signal-to-noise ratio response and signal amplification, therefore improving the analytical sensitivity and the response time. More importantly, their molecular size minimizes physical perturbation of living cells. Generally, fluorescent nanoparticles show superior optical properties, which facilitate their application for single molecule imaging and long-term tracking of biological molecules in vivo.[1] Our continued interest in the field of chemical approaches to target cancer cells [2][3][4][5][6][7][8][9] has led us to study the preparation of a novel class of squalene conjugated with paclitaxel, podophyllotoxin, camptothecin, and epothilone A. These conjugates were all functionalized with a squalene tail that enabled them to self-assemble in water, and to secure the release of the drug inside the cells through a disulfide-containing linker.[10] The need to trace the delivery of the nanoassemblies and to demonstrate the internalization of the drugs prompted us to prepare fluorescent heteronanoassemblies by mixing a paclitaxel-squalene conjugate and a fluorescein-squalene conjugate (Figure 1).We planned to use the recently described squalenoyl-paclitaxel 5 that was recognized as being able to act as a prodrug and to self-assemble.[11] The reaction of 1,1',2-tris-norsqualene alcohol 4 with fluorescein isothiocyanate (FITC) in the presence of sodium hydride gave the stable compound 6. To verify the ability of compound 6 (fluorescein conjugate) to form nanoassemblies and of compounds 5 and 6 to form heteronanoparticles, [12] five different nanosuspensions were prepared by the solvent displacement method. This consists in dissolving both the compounds in ethanol and removing organic solvent in vacuo after the addition of MilliQ water (Figure 2).Measurement of the mean diameter and polydispersity index by using quasielastic light scattering (QELS) confirmed the presence of self-assemblies (Table 1). It was evident that by decreasing the amount of fluorescein-squalene conjugate 6, the mean diameter...

Stereochemistry and complete 1H and 13C NMR signal assignment of C‐20‐oxime derivatives of posterone 2,3‐acetonide in solution state

“…These can be prepared by functionalizing a potential antitumor agent with a long lipophilic side‐chain through functional group(s) hydrolysable in a biological environment (e.g., ester), which will make them working as prodrugs once released. The role of the side‐chain in such a conjugate is to induce the self‐assembly to nanoparticles in aqueous environment due to secondary interactions . In our previous work, we applied two different types of linkers: one only with CH 2 units and another with S―S disulfide bridge in the middle of this unit.…”

A small library of chalcones induce liver cancer cell death through Akt phosphorylation inhibition

“…In this study, following our interest in the synthesis and the identification of compounds with anticancer related bioactivities [20][21][22][23][24][25][26][27][28][29][30][31][32] , eleven chalcones were synthesized and tested against HCC cell lines and dental pulp stem cells which are reported to be hepatic progenitor properties 33 . DPSCs can proliferate and differentiate rapidly into various lineages including hepatocytes therefore they present a good model for untransformed control cells 34 .…”

Self-assembly drug conjugates for anticancer treatment

“…Its inertness and biocompatibility justify the use of squalene derivatives (6) (18) with the inclusion of an alternative linker [40][41][42]. In this study, the squalene moiety and the active compound were connected by a disulfide-containing linker able to guarantee the drug release inside the cell.…”