Arsenoplatin-Ferritin Nanocage: Structure and Cytotoxicity

Ferraro, Giarita; Pratesi, Alessandro; Cirri, Damiano; Imbimbo, Paola; Monti, Daria Maria; Messori, Luigi; Merlino, Antonello

doi:10.3390/ijms22041874

Cited by 8 publications

(7 citation statements)

References 52 publications

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“…Recently, Ferraro and colleagues developed a novel FN loaded with Arsenoplatin-1 (Pt(µ-NHC(CH 3 )O) 2 ClAs(OH) 2 ), which combines the cytotoxic effects of both cisplatin and arsenic trioxide. Preliminary in vitro results showed that this novel formulation provides selectivity toward cancer cells, but, unfortunately, it was not tested in vivo [50].…”

Section: Fn-based Nps For Cancer Treatment In Preclinical Modelsmentioning

confidence: 99%

Protein-Based Nanoparticles for the Imaging and Treatment of Solid Tumors: The Case of Ferritin Nanocages, a Narrative Review

et al. 2021

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Protein nanocages have been studied extensively, due to their unique architecture, exceptional biocompatibility and highly customization capabilities. In particular, ferritin nanocages (FNs) have been employed for the delivery of a vast array of molecules, ranging from chemotherapeutics to imaging agents, among others. One of the main favorable characteristics of FNs is their intrinsic targeting efficiency toward the Transferrin Receptor 1, which is overexpressed in many tumors. Furthermore, genetic manipulation can be employed to introduce novel variants that are able to improve the loading capacity, targeting capabilities and bio-availability of this versatile drug delivery system. In this review, we discuss the main characteristics of FN and the most recent applications of this promising nanotechnology in the field of oncology with a particular emphasis on the imaging and treatment of solid tumors.

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Section: Fn-based Nps For Cancer Treatment In Preclinical Modelsmentioning

confidence: 99%

Protein-Based Nanoparticles for the Imaging and Treatment of Solid Tumors: The Case of Ferritin Nanocages, a Narrative Review

et al. 2021

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“…Recently, encouraging attempts have been made to hamper the selectivity of AP-1 for cancer cells. One promising strategy involves horse spleen apo-ferritin nanocages, which can be used to encapsulate arsenoplatins, leading to an effective improvement of the selectivity for the A431 (human epidermoid carcinoma) and SVT2 (murine BALB/c-3T3 fibroblasts transformed with SV40 virus) cancer cells with respect to HaCaT (immortalized human keratinocytes) and Balb/c-3T3 (immortalized murine BALB/c-3T3 fibroblasts) healthy cells [ 121 ].…”

Section: The Strategiesmentioning

confidence: 99%

Strategies for the Improvement of Metal-Based Chemotherapeutic Treatments

Cirri¹,

Bartoli²,

Pratesi³

et al. 2021

Biomedicines

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This article provides an overview of the various research approaches we have explored in recent years to improve metal-based agents for cancer or infection treatments. Although cisplatin, carboplatin, and oxaliplatin remain the cornerstones in tumor chemotherapy, the discovery and approval of novel inorganic anticancer drugs is a very slow process. Analogously, although a few promising inorganic drugs have found clinical application against parasitic or bacterial infections, their use remains relatively limited. Moreover, the discovery process is often affected by small therapeutic enhancements that are not attractive for the pharmaceutical industry. However, the availability of increasing mechanistic information for the modes of action of established inorganic drugs is fueling the exploration of various approaches for developing effective inorganic chemotherapy agents. Through a series of examples, some from our own research experience, we focus our attention on a number of promising strategies, including (1) drug repurposing, (2) the simple modification of the chemical structures of approved metal-based drugs, (3) testing novel drug combinations, and (4) newly synthesized complexes coupling different anticancer drugs. Accordingly, we aim to suggest and summarize a series of reliable approaches that are exploitable for the development of improved and innovative treatments.

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“…Another evidence of AP-1 targeting His residue was offered by a recent study, in which AP-1 was placed into the apoferritin (AFt) nanocage; the resulting X-ray structure revealed the coordination of the AP-1 fragment to the side chain of a His residue. 19 The present study has a twofold objective.…”

Section: Introductionmentioning

confidence: 99%

Reactions of Arsenoplatin-1 with Protein Targets: A Combined Experimental and Theoretical Study

et al. 2022

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Arsenoplatin-1 (AP-1) is a dual-action anticancer metallodrug with a promising pharmacological profile that features the simultaneous presence of a cisplatin-like center and an arsenite center. We investigated its interactions with proteins through a joint experimental and theoretical approach. The reactivity of AP-1 with a variety of proteins, including carbonic anhydrase (CA), superoxide dismutase (SOD), myoglobin (Mb), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and human serum albumin (HSA), was analyzed by means of electrospray ionization mass spectrometry (ESI MS) measurements. In accordance with previous observations, ESI MS experiments revealed that the obtained metallodrug–protein adducts originated from the binding of the [(AP-1)-Cl] + fragment to accessible protein residues. Remarkably, in two cases, i.e., Mb and GAPDH, the formation of a bound metallic fragment that lacked the arsenic center was highlighted. The reactions of AP-1 with various nucleophiles side chains of neutral histidine, methionine, cysteine, and selenocysteine, in neutral form as well as cysteine and selenocysteine in anionic form, were subsequently analyzed through a computational approach. We found that the aquation of AP-1 is energetically disfavored, with a reaction free energy of +19.2 kcal/mol demonstrating that AP-1 presumably attacks its biological targets through the exchange of the chloride ligand. The theoretical analysis of thermodynamics and kinetics for the ligand-exchange processes of AP-1 with His, Met, Cys, Sec, Cys – , and Sec – side chain models unveils that only neutral histidine and deprotonated cysteine and selenocysteine are able to effectively replace the chloride ligand in AP-1.

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Arsenoplatin-Ferritin Nanocage: Structure and Cytotoxicity

Cited by 8 publications

References 52 publications

Protein-Based Nanoparticles for the Imaging and Treatment of Solid Tumors: The Case of Ferritin Nanocages, a Narrative Review

Protein-Based Nanoparticles for the Imaging and Treatment of Solid Tumors: The Case of Ferritin Nanocages, a Narrative Review

Strategies for the Improvement of Metal-Based Chemotherapeutic Treatments

Reactions of Arsenoplatin-1 with Protein Targets: A Combined Experimental and Theoretical Study

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