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

Abstract

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.

Magneto-Plasmonic Nanoparticle Grid Biosensor with Enhanced Raman Scattering and Electrochemical Transduction for the Development of Nanocarriers for Targeted Delivery of Protected Anticancer Drugs

“…Biocompatible polyelectrolyte complex nanostructures and NPs with other coatings can also be designed to serve as the TDD nanocarriers [29,31]. On the other hand, biogenic nanocarriers, such as those based on apoferritin nanocage carriers [9], generally do not require any extra biocompatibility ligands. Doxorubicin, used in this work as the model chemotherapeutic drug, is one of the most widely used anticancer drugs [32].…”

“…A variety of nanoparticles (NPs) have been designed and investigated for applications as the nanocarriers in TDD, including liposomes [ 7 ], solid lipid NPs [ 8 ], empty-shell biomolecules, such as apoferritin [ 9 ] or cyclodextrin [ 10 ], biodegradable particles [ 11 ], polymeric dendrimer nanostructures [ 4 ], plasmonic [ 12 , 13 ] and magnetic [ 14 ] NPs, and others.…”

“…The immobilization of drugs, targeting ligands, and other functional molecules onto the nanoparticle nanocarriers involves various kinds of binding, including electrostatic interactions [ 15 , 16 ], covalent binding [ 12 , 13 , 14 , 17 , 18 ], adsorption [ 19 ], supramolecular interactions [ 9 , 20 ], and trapping [ 7 ]. The drug binding to nanocarriers and encapsulation processes have been carried out to improve pharmacological and therapeutic effects of the drugs in terms of reducing collateral damage and side effects [ 21 , 22 , 23 ], while increasing the local drug potency at the targeted cancer cells.…”

Magneto-Plasmonic Nanoparticle Grid Biosensor with Enhanced Raman Scattering and Electrochemical Transduction for Development of Nanocarriers for Targeted Delivery of Protected Anticancer Drugs

“…The immobilization of drugs, targeting ligands and other functional molecules onto the nanoparticle nanocarriers involves various kinds of binding, including electrostatic interactions [15,16], covalent binding [12][13][14][17][18][19], adsorption [20,21], supramolecular interactions [9,22], and trapping [7]. The drug binding to nanocarriers and encapsulation processes have been carried out to improve pharmacological and therapeutic effects of the drugs in terms of reducing collateral damage and side effects [23][24][25], while increasing the local drug potency at the targeted cancer cells.…”

“…Biocompatible polyelectrolyte complex nanostructures and NPs with other coatings can also be designed to serve as the TDD nanocarriers [31,33]. On the other hand, the biogenic nanocarriers, such as those based on apoferritin nanocage carriers [9], generally, do not require any extra biocompatibility ligands. Doxorubicin, used in this work as the model chemotherapeutic drug, is one of the most widely used anticancer drugs [34].…”