Mechanised nanoparticles for drug delivery

Abstract

Time and time again humanity is faced with a unifying global crisis that crosses the many great divides in different societies and serves to bring once segregated communities back together as a collective whole. This global community instinctively turns to science to develop the means of addressing its most pressing problems. More often than not, these forces dictate the direction that scientific research takes. This influence is no more apparent than in the field of supramolecular chemistry where, for decades now, its responsibility to tackle such issues has been put on the back burner as a consequence of a lack of platforms with which to deliver this contemporary brand of chemistry to meaningful applications. However, the tide is slowly turning as new materials emerge from the field of nanotechnology that are poised to host the many attractive attributes that are inherent in the chemistry of these supermolecules and also in the mechanostereochemistry of mechanically interlocked molecules (MIMs), which can be reused as a sequel to supramolecular chemistry. Mesoporous silica nanoparticles (SNPs) have proven to be supremely effective solid supports as their surfaces are easily functionalised with either supermolecules or MIMs. In turn, the blending of supramolecular chemistry and mechanostereochemistry with mesoporous SNPs has led to a new class of materials - namely, mechanised SNPs that are effectively biological nanoscale 'bombs' that have the potential to infiltrate cells and then, upon the pulling of a chemical trigger, explode! The development of these materials has been driven by the need to devise new therapies for the treatment of cancer. Recent progress in research promises not only to control the acuteness of this widespread and insidious disease, but also to make the harsh treatment less debilitating to patients. This global scourge is the unifying force that has brought together supramolecular chemistry, mechanostereochemistry and nanotechnology, uniting these three communities for the common good. At the nanoscale level, the mechanism for the release of cargos from the confines of the nanopores in the SNPs is accomplished by way of mechanical modifications made on the surface of these functionalised supports. These mechanical motions rely on both supramolecular, i.e., host-guest complexes, and mechanostereochemical phenomena (e.g., bistable rotaxanes), which are often stimulated by changes in pH, light and redox potentials, in addition to enzymatic catalysis. The future of this field lies in the development of 'smart bombs' wherein the loaded mechanised SNPs are endocytosed selectively by cancer cells, whereupon an intracellular trigger causes release of a cytotoxin, effectively leading to apoptosis. This review serves to highlight (1) the evolution of surface-functionalisation of SNPs with supermolecules and also with MIMs, (2) the mechanisms through which controlled-release of cargo from mechanised SNPs occurs, and (3) results from the in vitro application of these mechanised SNPs.

Measurement of the ground-state distributions in bistable mechanically interlocked molecules using slow scan rate cyclic voltammetry

“…6) between the GSCC and MSCC in the gas phase is 41.6 kcal∕mol favoring the GSCC. This large energetic difference is not observed for the case of the rotaxane R • 4PF 6 , where the gas-phase energy difference is only 13.8 kcal∕mol, also in favor of the GSCC. These relative gasphase energies suggest that there are electronic effects in the catenane that are not present in the rotaxane, which cause the GSCC to be more stable by approximately 28 kcal/mol.…”

“…We prepared samples of the bistable [2]rotaxane R • 4PF 6 and two bistable [2]catenanes, C1 • 4PF 6 and C2 • 4PF 6 , to revisit their ground-state distribution constants. R 4þ along with C1 4þ both contain DNP as the alternative π-electron-rich unit, whereas C2 4þ incorporates the much less π-electron-rich butadiyne unit.…”

“…The crude product was purified by preparative RP-HPLC, and R • 4PF 6 was characterized by both 1 H and 13 C NMR spectroscopies, as well as by high-resolution electrospray ionization mass spectrometry. The purity of R • 4PF 6 , C1 • 4PF 6 , and C2 • 4PF 6 were all determined (see SI Text) by analytical RP-HPLC and 1 H NMR spectroscopy.…”

“…Initially, we investigated the gas-phase and MeCN solvation energy differences between the GSCC and MSCC for catenane C1 • 4PF 6 . Using the M06 functional (43,44) and the 6-311 þ þG ÃÃ basis set, our results show that the energy difference (Fig.…”

“…This control is essential to the development of potential applications as diverse as catalysis (5), drug delivery (6), elastic materials (7), molecular actuators (8), molecular transport (9), ion sensors (10), motors (11), and information storage (12). Supramolecular chemistry (13) has been one of the sources from which the inspiration and desire to build artificial molecular machines, as the counterpart to biological motors, has sprung.…”