Antitumor activity of photodynamic therapy performed with nanospheres containing zinc-phthalocyanine

Author(s):Show less -

Portilho, Flavia Arruda ^[1] ; de Oliveira Cavalcanti, Claudio Eduardo ^{[1, 2, 3]} ; Miranda-Vilela, Ana Luisa ^{[1, 4]} ; Carneiro Estevanato, Luciana Landim ^[1] ; Figueiro Longo, Joao Paulo ^[1] ; Menezes Almeida Santos, Maria de Fatima ^[1] ; Bocca, Anamelia Lorenzetti ^[5] ; Martins, Olimpia Paschoal ^[6] ; Simioni, Andreza R. ^[6] ; Morais, Paulo Cesar ^{[7, 8]} ; Azevedo, Ricardo Bentes ^[1] ; Tedesco, Antonio Claudio ^[6] ; Marques Lacava, Zulmira Guerrero ^[1]

Affiliation

^[1] Univ Brasilia, Inst Ciencias Biol, Dept Genet & Morfol, BR-70910970 Brasilia, DF - Brazil

^[2] Univ Fed Alagoas, Fac Med, BR-57072970 Maceio, AL - Brazil

^[3] Univ Estadual Ciencias Saude Alagoas UNCISAL, BR-57010300 Maceio, AL - Brazil

^[4] Fac Integradas Uniao Educ Planalto Cent Faciplac, Curso Med, Brasilia, DF - Brazil

^[5] Univ Brasilia, Inst Ciencias Biol, Dept Biol Celular, BR-70910900 Brasilia, DF - Brazil

^[6] Univ Sao Paulo, Ctr Nanotecnol & Engn Tecidual, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, Lab Fotobiol & Fotomed, BR-14040901 Ribeirao Preto, SP - Brazil

^[7] Univ Brasilia, Inst Fis, Nucleo Fis Aplicada, BR-70910900 Brasilia, DF - Brazil

^[8] Huazhong Univ Sci & Technol, Sch Automat, Wuhan 430074 - Peoples R China

• Document type: Journal article
• Source: JOURNAL OF NANOBIOTECHNOLOGY; v. 11, DEC 16 2013.
• Web of Science Citations: 20

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. (AU)

• FAPESP's process: 08/53719-4 - Use of nanocarriers containing photosensitive dyes and other derived and growing factors applied to the photodynamic process in the health areas
• Grantee: Antonio Claudio Tedesco
• Support Opportunities: Research Projects - Thematic Grants