Cancer-Targeted Controlled Delivery of Chemotherapeutic Anthracycline Derivatives Using Apoferritin Nanocage Carriers

The interactions of chemotherapeutic drugs with nanocage protein apoferritin (APO) are the key features in the effective encapsulation and release of highly toxic drugs in APO-based controlled drug delivery systems. The encapsulation enables mitigating the drugs’ side effects, collateral damage to healthy cells, and adverse immune reactions. Herein, the interactions of anthracycline drugs with APO were studied to assess the effect of drug lipophilicity on their encapsulation excess n and in vitro activity. Anthracycline drugs, including doxorubicin (DOX), epirubicin (EPI), daunorubicin (DAU), and idarubicin (IDA), with lipophilicity P from 0.8 to 15, were investigated. We have found that in addition to hydrogen-bonded supramolecular ensemble formation with n = 24, there are two other competing contributions that enable increasing n under strong polar interactions (APO(DOX)) or under strong hydrophobic interactions (APO(IDA) of the highest efficacy). The encapsulation/release processes were investigated using UV-Vis, fluorescence, circular dichroism, and FTIR spectroscopies. The in vitro cytotoxicity/growth inhibition tests and flow cytometry corroborate high apoptotic activity of APO(drugs) against targeted MDA-MB-231 adenocarcinoma and HeLa cells, and low activity against healthy MCF10A cells, demonstrating targeting ability of nanodrugs. A model for molecular interactions between anthracyclines and APO nanocarriers was developed, and the relationships derived compared with experimental results.

Switchable supramolecular ensemble for anion binding with ditopic hydrogen-bonded macrocycles

Hydrogen-bonded (H-bonded) macrocycles that recognize cationic and/or anionic species via non-covalent interactions have found a variety of applications in separation, catalysis, analysis and creation of functional molecules. One of the...

Calix[n]triazolium based Turn-On Fluorescent Sensing Ensemble for Selective Adenosine Monophosphate (AMP) Detection

A novel calix[n]triazolium was synthesized and exhibited excellent selectivity for AMP. The binding between calix[n]triazolium and chromenolate anion forms a non-fluorescent complex and the resulting supramolecular ensemble selectively detects AMP...

Cancer-targeted Controlled Delivery of Chemotherapeutic Anthracycline DerivativesUsing Apoferritin Nanocage Carriers

The interactions of chemotherapeutic drugs with nanocage protein apoferritin (APO) are the key features in the effective encapsulation and release of highly toxic drugs in APO-based controlled drug delivery systems. The encapsulation enables mitigating the drugs side effects, collateral damage to healthy cells, and adverse immune reactions. Herein, the interactions of anthracycline drugs with APO were studied to assess the effect of drug lipophilicity on their encapsulation excess n and in vitro activity. Anthracycline drugs, including doxorubicin (DOX), epirubicin (EPI), daunorubicin (DAU), and idarubicin (IDA), with lipophilicity P from 0.8 to 15, were investigated. We have found that in addition to hydrogen-bonded supramolecular ensemble formation with n = 24, there are two other competing contributions that enable increasing n under strong polar interactions (APO(DOX)) or under strong hydrophobic interactions (APO(IDA) of the highest efficacy). The encapsulation/release processes were investigated using UV-Vis, fluorescence, circular dichroism, and FTIR spectroscopies. In vitro cytotoxicity/growth inhibition tests and flow cytometry corroborate high apoptotic activity of APO(drugs) against targeted MDA-MB-231 adenocarcinoma and HeLa cancer cells, and low activity against non-tumorigenic MCF10A cells, demonstrating targeting ability of nanodrugs. A model for molecular interactions between anthracyclines and APO nanocarriers was developed, and the relationships derived compared with experimental results.

Confining enzyme clusters in supramolecular nanoreactors enhances cofactor-dependent cascade for chiral alcohol synthesis

Enzymes in living organisms work efficiently in confined environments through spatial organization. Constituting a bio-cascade reaction in nano-confined space in vitro for the efficient synthesis of high-value chiral chemicals is challenging. Herein, we confined a cofactor-dependent cascade in bacteriophage P22 nanoparticles for the synthesis of chiral alcohols. Compared to free enzymes, this supramolecular ensemble, P22-SP-BmGDH-SsCR, exhibited enhanced catalytic efficiency up to 14.5-fold towards various ketones and improved stereoselectivity up to > 99% ee towards 8 substrates, and 10 chiral alcohols with > 96% ee were synthesized. The recycling efficiency of nicotinamide adenine dinucleotide phosphate (NADPH) was increased by 7.5-fold. We demonstrated that the enhancement in cofactor recycling originates from the higher local concentration of NADPH in the nanoparticles due to the proximity effect of enzymes and confinement of nanoparticles. The preparative synthesis of chiral alcohols showed that the consumption of NADPH can be reduced by one magnitude compared with the conventional free enzyme system.

A supramolecular approach towards strong and tough polymer nanocomposite fibers

Strong, tough and flexible polymer nanocomposite fibers can be approached by electrospinning of supramolecular ensemble of CNT–AIE–CNC/PVA in an aqueous system, which could be used for sensing.