title: Antitumor activity of photodynamic therapy performed with nanospheres containing zinc-phthalocyanine.
abstract: BACKGROUND
  The increasing incidence of cancer and the search for more effective therapies with minimal collateral effects have prompted studies to find alternative new treatments. Among these, photodynamic therapy (PDT) has been proposed as a very promising new modality in cancer treatment with the lowest rates of side effects, revealing itself to be particularly successful when the photosensitizer is associated with nanoscaled carriers. This study aimed to design and develop a new formulation based on albumin nanospheres containing zinc-phthalocyanine tetrasulfonate (ZnPcS4-AN) for use in the PDT protocol and to investigate its antitumor activity in Swiss albino mice using the Ehrlich solid tumor as an experimental model for breast cancer.
  
  
  METHODS
  Ehrlich tumor's volume, histopathology and morphometry were used to assess the efficacy of intratumoral injection of ZnPcS4-AN in containing tumor aggressiveness and promoting its regression, while the toxicity of possible treatments was assessed by animal weight, morphological analysis of the liver and kidneys, hemogram, and serum levels of total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, creatinine and urea. In order to evaluate the efficacy of PDT, groups of animals treated with intratumoral injection of doxorubicin (Dox) were also investigated.
  
  
  RESULTS
  Intratumoral injection of ZnPcS4-AN was found to be efficient in mediating PDT to refrain tumor aggressiveness and to induce its regression. Although tumor volume reduction was not significant, PDT induced a remarkable increase in the necrosis area seen in the tumor's central region, as in other experimental groups, including tumor and Dox treated groups, but also in the tumor's peripheral region. Further, PDT showed minimal adverse effects. Indeed, the use of ZnPcS4-AN in mediating PDT revealed anti-neoplastic activity similar to that obtained while using intratumoral Dox therapy.
  
  
  CONCLUSIONS
  PDT mediated by the new formulation ZnPcS4-AN enhanced the inhibition of tumor growth while producing practically no adverse effects and thus emerges as a very promising nanotechnology-based strategy for solid cancer treatment.
authors.forename: Flávia Arruda
authors.initials: FA
authors.lastname: Portilho
authors.forename: Cláudio Eduardo de Oliveira
authors.initials: CE
authors.lastname: Cavalcanti
authors.forename: Ana Luisa
authors.initials: AL
authors.lastname: Miranda-Vilela
authors.forename: Luciana Landim Carneiro
authors.initials: LL
authors.lastname: Estevanato
authors.forename: João Paulo Figueiró
authors.initials: JP
authors.lastname: Longo
authors.forename: Maria de Fátima Menezes
authors.initials: Mde F
authors.lastname: Almeida Santos
authors.forename: Anamélia Lorenzetti
authors.initials: AL
authors.lastname: Bocca
authors.forename: Olímpia Paschoal
authors.initials: OP
authors.lastname: Martins
authors.forename: Andreza R
authors.initials: AR
authors.lastname: Simioni
authors.forename: Paulo César
authors.initials: PC
authors.lastname: Morais
authors.forename: Ricardo Bentes
authors.initials: RB
authors.lastname: Azevedo
authors.forename: Antonio Claudio
authors.initials: AC
authors.lastname: Tedesco
authors.affiliation: Instituto de Ciências Biológicas, Departamento de Genética e Morfologia, Universidade de Brasília, CEP: 70910-970 Brasília, DF, Brazil. zulmira@unb.br.
authors.forename: Zulmira Guerrero Marques
authors.initials: ZG
authors.lastname: Lacava
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000418:Albumins / Q000737:chemistry*; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000473:pathology; D003404:Creatinine / Q000097:blood; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D015552:Injections, Intralesional; D008027:Light; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D054118:Nanospheres / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D014508:Urea / Q000097:blood; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000418:Albumins; D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C052735:zinc tetrasulfophthalocyanine; D004317:Doxorubicin; D014508:Urea; D003404:Creatinine; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin