Poly(alkylidenimine) Dendrimers Functionalized with the Organometallic Moiety [Ru(η5-C5H5)(PPh3)2]+ as Promising Drugs Against Cisplatin-Resistant Cancer Cells and Human Mesenchymal Stem Cells

Gouveia, Marisol; Figueira, José Rui; Jardim, Manuel G.; Castro, Rita; Tomás, Helena; Rodrigues, João

doi:10.3390/molecules23061471

Cited by 33 publications

(26 citation statements)

References 93 publications

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“…Metallodendrimers based on ruthenium to incorporate metals into dendritic scaffolds has been synthetize (Scheme 7) and characterize [105]. Several complexes based on ruthenium are in clinical phases against cancer therapies, however some complexes have had cytotoxicity problems.…”

Section: Dendrimer As Drug Delivery Systems To Cancer Treatmentsmentioning

confidence: 99%

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Dendrimers: Amazing Platforms for Bioactive Molecule Delivery Systems

Sandoval-Yáñez

Rodríguez

2020

Materials

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Today, dendrimers are the main nanoparticle applied to drug delivery systems. The physicochemical characteristics of dendrimers and their versatility structural modification make them attractive to applied as a platform to bioactive molecules transport. Nanoformulations based on dendrimers enhance low solubility drugs, arrival to the target tissue, drugs bioavailability, and controlled release. This review describes the latter approaches on the transport of bioactive molecules based on dendrimers. The review focus is on the last therapeutic strategies addressed by dendrimers conjugated with bioactive molecules. A brief review of the latest studies in therapies against cancer and cardiovascular diseases, as well as future projections in the area, are addressed.

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Section: Dendrimer As Drug Delivery Systems To Cancer Treatmentsmentioning

confidence: 99%

“…Schematic representation of metallodendrimer base on poly(alkylidenimine) dendrimer core containing nitrile groups and functionalized with [Ru(η 5 -C 5 H 5 )(PPh 3 ) 2 Cl] compound. This scheme was provided thanks to Reference [105]. Scheme 8.…”

Section: Dendrimer As Drug Delivery Systems To Cancer Treatmentsmentioning

confidence: 99%

Dendrimers: Amazing Platforms for Bioactive Molecule Delivery Systems

Sandoval-Yáñez

Rodríguez

2020

Materials

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“…Dendrimers have been investigated for the delivery of metallocomplexes [109][110][111][112][113][114]. For example, Gouveia et al produced low generation dendrimers modified with an organometallic compound of Ru(II) [110]. The nitrile poly(alkylidenimine) dendritic scaffolds of different sizes were modified with an organometallic fragment [Ru(η 5 -C 5 H 5 )(PPh 3 ) 2 ] + attached to the peripheral end groups of the dendrimers.…”

Section: Dendrimersmentioning

confidence: 99%

Nano-Based Systems and Biomacromolecules as Carriers for Metallodrugs in Anticancer Therapy

2018

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Since the discovery of cisplatin and its potency in anticancer therapy, the development of metallodrugs has been an active area of research. The large choice of transition metals, oxidation states, coordinating ligands, and different geometries, allows for the design of metal-based agents with unique mechanisms of action. Many metallodrugs, such as titanium, ruthenium, gallium, tin, gold, and copper-based complexes have been found to have anticancer activities. However, biological application of these agents necessitates aqueous solubility and low systemic toxicity. This minireview highlights the emerging strategies to facilitate the in vivo application of metallodrugs, aimed at enhancing their solubility and bioavailability, as well as improving their delivery to tumor tissues. The focus is on encapsulating the metal-based complexes into nanocarriers or coupling to biomacromolecules, generating efficacious anticancer therapies. The delivery systems for complexes of platinum, ruthenium, copper, and iron are discussed with most recent examples. explored as possible alternatives, but none have yet entered the clinic. Importantly, high efficacy of platinum paved the way for the development of other transition metal complexes, many with outstanding cytotoxic properties against cancer cells.Transition metals form complexes of multiple geometries based on the number of coordination sites, offering a stereoisomeric diversity higher than carbon. In addition, a synthesis of metallodrugs requires fewer steps when compared to organic compounds. This is accompanied by a myriad choice of coordinating ligands [17] facilitating fine-tuning the properties of metal-based complexes [17,18]. The octahedral titanium species cis-diethoxy-bis(1-phenylbutane-1,3-dionato)titanium(IV) [(bzac) 2 Ti(OEt) 2 ] (budotitane), was the first non-Pt(II) metal compound that reached clinical trials [19]. Following this, ruthenium-based complexes were explored showing fewer side effects when compared to platinum-based agents and activity against Pt-resistant cancers [20][21][22]. Two ruthenium derivates, imidazolium trans-DMSO-imidazole-tetrachlororuthenate (NAMI-A) and imidazolium trans-[tetrachlorido(DMSO)(1H-imidazole)ruthenate(III)] (KP-1019), have been tested in clinical trials [22,23]. KP-1019 showed efficacy towards primary tumors, such as colon cancer, without triggering systemic toxicity, while NAMI-A was not cytotoxic but demonstrated activity against metastases. Moreover, NKP-1339 (the sodium salt analogue of KP1019, sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)]) has successfully completed a phase I clinical trial [24]. NKP-1339 is Ru(III) that binds to serum proteins albumin and transferrin, which transport and deliver the metallodrug to the tumor tissue. Once inside endosomes, NKP-1339 reduces to Ru(II). Recently, new designs of ruthenium complexes are emerging that include Ru(η 5 -C 5 H 5 ) core. This class of Ru(II) compounds demonstrates enhanced selectivity and effectiveness, for example ruthenium pyridocarbazole (DW1/2...

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“…The therapeutic agents may either be encapsulated into the three-dimensional void spaces of the dendrimers or conjugated or physically adsorbed (electrostatic interactions) onto the surface of the dendrimer [ 11 , 12 ]. Another strategy is to develop dendrimers, such as drugs, active per se in several therapeutic realms [ [13] , [14] , [15] , [16] , [17] , [18] , [19] ]. Over the last several years, we have embarked on this direction in order to develop new drugs based on phosphorus dendrimers, for instance, as anticancer [ 20 , 21 ] and anti-inflammatory agents [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Non-invasive intranasal administration route directly to the brain using dendrimer nanoplatforms: An opportunity to develop new CNS drugs

Mignani

Shi

Karpus

et al. 2021

European Journal of Medicinal Chemistry

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There are several routes of administration to the brain, including intraparenchymal, intraventricular, and subarachnoid injections. The blood-brain barrier (BBB) impedes the permeation and access of most drugs to the central nervous system (CNS), and consequently, many neurological diseases remain undertreated. For past decades, to circumvent this effect, several nanocarriers have been developed to deliver drugs to the brain. Importantly, intranasal (IN) administration can allow direct delivery of drugs into the brain through the anatomical connection between the nasal cavity and brain without crossing the BBB. In this regard, dendrimers may possess great potential to deliver drugs to the brain by IN administration, bypassing the BBB and reducing systemic exposure and side effects, to treat diseases of the CNS. In this original concise review, we highlighted the few examples advocated regarding the use of dendrimers to deliver CNS drugs directly via IN. This review highlighed the few examples of the association of dendrimer encapsulating drugs ( e.g. , small compounds: haloperidol and paeonol; macromolecular compounds: dextran, insulin and calcitonin; and siRNA) using IN administration. Good efficiencies were observed. In addition, we will present the in vivo effects of PAMAM dendrimers after IN administration, globally, showing no general toxicity.

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Poly(alkylidenimine) Dendrimers Functionalized with the Organometallic Moiety [Ru(η5-C5H5)(PPh3)2]+ as Promising Drugs Against Cisplatin-Resistant Cancer Cells and Human Mesenchymal Stem Cells

Cited by 33 publications

References 93 publications

Dendrimers: Amazing Platforms for Bioactive Molecule Delivery Systems

Dendrimers: Amazing Platforms for Bioactive Molecule Delivery Systems

Nano-Based Systems and Biomacromolecules as Carriers for Metallodrugs in Anticancer Therapy

Non-invasive intranasal administration route directly to the brain using dendrimer nanoplatforms: An opportunity to develop new CNS drugs

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