Controlled drug release to cancer cells from modular one-photon visible light-responsive micellar system

Abstract

We present a one-photon visible light-responsive micellar system for efficient, on-demand delivery of small molecules. Release is mediated by a novel class of photochromic material - donor-acceptor Stenhouse adducts (DASAs). We demonstrate controlled delivery of small molecules such as the chemotherapeutic agent (paclitaxel) to human breast cancer cells triggered by micellar switching with low intensity, visible light.

A Versatile Approach for In Situ Monitoring of Photoswitches and Photopolymerizations

“…Herein we report a simple NMR‐based technique to monitor photochemical transformations in situ using inexpensive and universal optical‐fiber inserts, coupled with modular, computer‐controlled LED irradiation. To illustrate the utility of this strategy, the Φ of two photochromic small molecules, a donor–acceptor Stenhouse adduct (DASA) as well as a diarylethene (DAE), were determined from optically dense propagating fronts. Complementing the small‐molecule studies, this new technique was also used to analyze several light‐driven controlled polymerizations, leading to kinetic insights and a detailed understanding of molecular weight, structure, and dispersity evolution with conversion .…”

It's a Trap: Thiol‐Michael Chemistry on a DASA Photoswitch

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Donor-acceptor Stenhousea dducts( DASA) are popularp hotoswitches capable of togglingb etween two isomersd epending on the light and temperature of the system.T he cyclized polar form is accessed by visible-light irradiation, whereas the linear nonpolar form is recovered in the dark. [2][3][4][5] Photoswitches, such as derivatives of the donor-acceptor Stenhouse adduct (DASA), coexisti na ne quilibrium between two isomeric forms.O ne isomer consists of an intensely colored (blue, purple or orange)n onpolar linear form, whereas the other isomer is cyclized, polar,c olorless and commonly zwitterionic (Scheme 1). The thiol-Michael addition was carried out with an alkyl (1-butanethiol) and an aromatic thiol (p-bromothiophenol) as reaction partners, both in the presence of ab ase.

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“…[6][7][8][9] The equilibrium between the two forms is dependent on the solvente nvironment andt he structural motifs of the DASA derivatives, consistingo fa ne lectron donor and an acceptorm oiety,r esultingi napush-pull system.U pon irradiation, the equilibrium is shifted towardst he ring cyclized isomer (cyclized form) and, upon thermalr elaxation, it returns to the initialc onjugated state (linear form). [8,9,14,15] The inherent advantages of DASA photoswitches, which includesn egative photochromism, inexpensives tarting materials, modular synthesis, tunable absorption, visible-light switching, and good fatiguer esistance, are appealing for ar ange of applications.T odate, polarity and color are the main adjustable propertieso fD ASAs explored for applications including micelles formation, targeting biomedical applications, [4,16] pH and temperature sensors, [5,17] and visible-light responsive devices. [32] The current consensus on the cyclization processi nvolves isomerizationo ft he double bonds, followedby ab ond rotation, and finallyathermal conrotatory4 p electrocyclization leading to the cyclized ring, commonly stabilizedb yi ts zwitterionic form through ap roton transfer.…”

Synthesis and Applications of Stenhouse Salts and Derivatives

“…The photophysical properties of DASAs and CPs allowed several applications to be envisaged using this reversible controlled system, such as colorimetric detection of amines, polymer assisted detection of nerve agents and pressure/heat, photolithography on polymers and light responsive supramolecular systems . Adsorption of chemical entities on surfaces such as polymers is of great importance particularly on light responsive systems.…”

“…The paclitaxel loaded micelles upon irradiation with visible light presented toxicity comparable to paclitaxel alone, proving the efficient release of the cytotoxic upon irradiation. The toxicity was significantly lower when no light was applied, ruling out the unselective release of the small molecule from the micelle …”