title: Free Rhodium (II) citrate and rhodium (II) citrate magnetic carriers as potential strategies for breast cancer therapy.
abstract: BACKGROUND
  Rhodium (II) citrate (Rh(2)(H(2)cit)(4)) has significant antitumor, cytotoxic, and cytostatic activity on Ehrlich ascite tumor. Although toxic to normal cells, its lower toxicity when compared to carboxylate analogues of rhodium (II) indicates (Rh(2)(H(2)cit)(4)) as a promising agent for chemotherapy. Nevertheless, few studies have been performed to explore this potential. Superparamagnetic particles of iron oxide (SPIOs) represent an attractive platform as carriers in drug delivery systems (DDS) because they can present greater specificity to tumor cells than normal cells. Thus, the association between Rh(2)(H(2)cit)(4) and SPIOs can represent a strategy to enhance the former's therapeutic action. In this work, we report the cytotoxicity of free rhodium (II) citrate (Rh(2)(H(2)cit)(4)) and rhodium (II) citrate-loaded maghemite nanoparticles or magnetoliposomes, used as drug delivery systems, on both normal and carcinoma breast cell cultures.
  
  
  RESULTS
  Treatment with free Rh(2)(H(2)cit)(4) induced cytotoxicity that was dependent on dose, time, and cell line. The IC(50) values showed that this effect was more intense on breast normal cells (MCF-10A) than on breast carcinoma cells (MCF-7 and 4T1). However, the treatment with 50 μM Rh(2)(H(2)cit)(4)-loaded maghemite nanoparticles (Mag(h)-Rh(2)(H(2)cit)(4)) and Rh(2)(H(2)cit)(4)-loaded magnetoliposomes (Lip-Magh-Rh(2)(H(2)cit)(4)) induced a higher cytotoxicity on MCF-7 and 4T1 than on MCF-10A (p < 0.05). These treatments enhanced cytotoxicity up to 4.6 times. These cytotoxic effects, induced by free Rh(2)(H(2)cit)(4), were evidenced by morphological alterations such as nuclear fragmentation, membrane blebbing and phosphatidylserine exposure, reduction of actin filaments, mitochondrial condensation and an increase in number of vacuoles, suggesting that Rh(2)(H(2)cit)(4) induces cell death by apoptosis.
  
  
  CONCLUSIONS
  The treatment with rhodium (II) citrate-loaded maghemite nanoparticles and magnetoliposomes induced more specific cytotoxicity on breast carcinoma cells than on breast normal cells, which is the opposite of the results observed with free Rh(2)(H(2)cit)(4) treatment. Thus, magnetic nanoparticles represent an attractive platform as carriers in Rh(2)(H(2)cit)(4) delivery systems, since they can act preferentially in tumor cells. Therefore, these nanopaticulate systems may be explored as a potential tool for chemotherapy drug development.
authors: Instituto de Ciências Biológicas, Universidade de Brasília, Brazil, 70.919-970. marbretas@gmail.com
authors: Marcella L B
authors: ML
authors: Carneiro
authors: Eloiza S
authors: ES
authors: Nunes
authors: Raphael C A
authors: RC
authors: Peixoto
authors: Ricardo G S
authors: RG
authors: Oliveira
authors: Luiza H M
authors: LH
authors: Lourenço
authors: Izabel C R
authors: IC
authors: da Silva
authors: Andreza R
authors: AR
authors: Simioni
authors: Antônio C
authors: AC
authors: Tedesco
authors: Aparecido R
authors: AR
authors: de Souza
authors: Zulmira G M
authors: ZG
authors: Lacava
authors: Sônia N
authors: SN
authors: Báo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001940:Breast / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D002460:Cell Line; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008081:Liposomes / Q000009:adverse effects / Q000627:therapeutic use; D058185:Magnetite Nanoparticles / Q000627:therapeutic use* / Q000648:ultrastructure; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D012238:Rhodium / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D058185:Magnetite Nanoparticles; D012238:Rhodium