A Liposome Encapsulated Ruthenium Polypyridine Complex as a Theranostic Platform for Triple-Negative Breast Cancer

Shen, Jianliang; Kim, Han Cheon; Wolfram, Joy; Mu, Chaofeng; Zhang, Wei; Liu, Haoran; Xie, Yan; Mai, Junhua; Zhang, Hang; Li, Zhi; Guevara, María L.; Mao, Zong‐Wan; Shen, Haifa

doi:10.1021/acs.nanolett.7b00132

Cited by 120 publications

(78 citation statements)

References 51 publications

(95 reference statements)

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“…The application of nanostructures improves the delivery and penetration of Ru(II) complexes, 336,337 thus increasing the concentration in cells. For example, the combination of nanomedicine and Ru(II) complexes yields significant anticancer efficacy in drug resistant cancer cells as they are not substrates for MDR transporters.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

The development of anticancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials

et al. 2017

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Cancer is rapidly becoming the top killer in the world. Most of the FDA approved anticancer drugs are organic molecules, while metallodrugs are very scarce. The advent of first metal based therapeutic agent, cisplatin, launched a new era in the application of transition metal complexes for therapeutic design. Due to their unique and versatile biochemical properties, ruthenium-based compounds have emerged as promising anti-cancer agents that serve as alternatives to cisplatin and its derivertives. The ruthenium(III) complexes have successfully been used in clinical research and their mechanisms of anticancer action have been reported in large volumes over the past few decades. Ruthenium(II) complexes have also attracted significant attention as anticancer candidates; however, only few of them have been reported comprehensively. In this review, we discuss the development of ruthenium(II) complexes as anticancer candidates and biocatalysts, including arene ruthenium complexes, polypyridyl ruthenium complexes, and ruthenium nanomaterial complexes. This review focuses on the likely mechanisms of action of ruthenium(II)-based anticancer drugs and the relationship between their chemical structures and biological properties. This review also highlights the catalytic activity and the photoinduced activation of ruthenium(II) complexes, their targeted delivery, and their activity in nanomaterial systems.

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Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

The development of anticancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials

et al. 2017

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“…The liposomal formulations of Ru have also been proposed [51,52] Shen et al demonstrated encapsulation of ruthenium polypirydine complex [Ru(phen) 2 dppz](ClO 4 ) 2 in a liposome carrier (Lipo-Ru), composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol, and distearoylphosphatidylethanolamine (DSPE)-PEG (polyethylene glycol). The schematic of the Lipo-Ru is presented in Figure 2A.…”

Section: Liposomesmentioning

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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“…In this way, NPMBC seem to have good in vivo pharmacokinetic properties. They are absorbed quickly into plasma [16,39,44,52], the circulation time in the bloodstream is long [42], their uptake in the tumor tissue is significant [16,28,32,37,39,41,42,44,46,51,52,60,70], their accumulation in organs (brain, liver, kidney, spleen, heart, lung, and intestine) is low [16,28,39,41,42,44,51,52,55] and the clearing rate is good [51].…”

Section: Anticancer Effects Of Non-platinum Mbc (Npmbc)mentioning

confidence: 99%

“…Furthermore, due to the lack of specific molecular targets in this subtype of BC [7], which makes its treatment difficult, chemotherapy remains an essential component for the management of TNBC, both adjuvant and neoadjuvant therapy [8,9]. Besides their diagnostic use [14][15][16][17][18][19][20][21], metallodrugs or metal-based complexes (MBC) stand out for being promising chemotherapeutic agents [22]. The therapeutic potential of MBC has long been known; however, their role in the treatment of cancer is relatively recent (1960s).…”

Section: Introductionmentioning

confidence: 99%

“…However, both cisplatin chemotherapies and its analogs have been shown to have major drawbacks (i.e., intrinsic and acquired chemoresistance, high general toxicity and limited spectrum of activity) [26] which have motivated extensive investigations into alternative metal-based cancer therapies that effectively target both cancer cell proliferation and metastasis. In this sense, we can mention chemotherapy with gold compounds [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46]-because they are nontoxic, nonimmunogenic and have good photothermal and optical properties, biocompatibility and stability [40,47,48]-and also with copper [49][50][51], ruthenium [16,[52][53][54][55][56][57][58][59], iron [56,[60][61][62][63][64][65], palladium [50], silver [66,…”

Section: Introductionmentioning

confidence: 99%

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Non-Platinum Metal Complexes as Potential Anti-Triple Negative Breast Cancer Agents

et al. 2018

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Breast cancer (BC) is the most common cancer in women worldwide, with a mortality rate that has been forecasted to rise in the next decade. This is especially worrying for people with triple-negative BC (TNBC), because of its unresponsiveness to current therapies. Different drugs to treat TNBC have been assessed, and, although platinum chemotherapy drugs seem to offer some hope, their drawbacks have motivated extensive investigations into alternative metal-based BC therapies. This paper aims to: (i) describe the preliminary in vitro and in vivo anticancer properties of non-platinum metal-based complexes (NPMBC) against TNBC; and (ii) analyze the likely molecular targets involved in their anticancer activity.

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A Liposome Encapsulated Ruthenium Polypyridine Complex as a Theranostic Platform for Triple-Negative Breast Cancer

Cited by 120 publications

References 51 publications

The development of anticancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials

The development of anticancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials

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

Non-Platinum Metal Complexes as Potential Anti-Triple Negative Breast Cancer Agents

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