ABSTRACT
This work describes the effects of immunotherapy with Protein Aggregate Magnesium-Ammonium Phospholinoleate-Palmitoleate Anhydride in the treatment of non-muscle invasive bladder cancer in an animal model. NMIBC was induced by treating female Fischer 344 rats with N-methyl-N-nitrosourea. After treatment with MNU, the rats were distributed into four experimental groups: Control (without MNU) group, MNU (cancer) group, MNU-BCG (Bacillus Calmette-Guerin) group, and MNU-P-MAPA group. P-MAPA intravesical treatment was more effective in histopathological recovery from cancer state in relation to BCG treatment. Western blot assays showed an increase in the protein levels of c-Myc, COUP-TFII, and wild-type p53 in P-MAPA-treated rats in relation to BCG-treated rats. In addition, rats treated with P-MAPA intravesical immunotherapy showed the highest BAX protein levels and the lowest proliferation/apoptotic ratio in relation to BCG-treated rats, pointing out a preponderance of apoptosis. P-MAPA intravesical treatment increased the wild-type p53 levels and enhanced c-Myc/COUP-TFII-induced apoptosis mediated by p53. These alterations were fundamental for histopathological recovery from cancer and for suppress abnormal cell proliferation. This action of P-MAPA on apoptotic pathways may represent a new strategy for treating NMIBC.
Subject(s)
Immunomodulating Agents/administration & dosage , Linoleic Acids/administration & dosage , Oleic Acids/administration & dosage , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/therapy , Administration, Intravesical , Animals , Apoptosis/drug effects , Cell Proliferation/drug effects , Disease Models, Animal , Female , Immunotherapy/methods , Neoplasm Invasiveness , Proto-Oncogene Proteins c-myc/metabolism , Rats, Inbred F344 , Repressor Proteins/metabolism , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Proteins/metabolism , Urinary Bladder Neoplasms/metabolism , bcl-2-Associated X Protein/metabolismABSTRACT
Plasmonic gold nanoparticles present extraordinary potential for near-infrared photothermal and triggered-therapeutic release treatments of solid tumors. In this study, we create a multifunctional nanocarrier in which PEG-coated gold nanorods are grouped into natural cell membrane vesicles (CM) from lung cancer (A549) cells and loaded with ß-lapachone (CM-ß-Lap-PEG-AuNRs). ß-Lapachone (ß-Lap) is an anticancer agent activated by the enzyme NADP(H):quinine oxidoreductase (NQO1), commonly found at higher levels in cancer cells. The irradiation with near-infrared (NIR) laser leads to disruption of the vesicles and release of the PEG-AuNRs and ß-Lap. The system presents an enhanced in vitro cytotoxicity against A549 cancer cells, which can be attributed to the specific cytotoxicity of ß-Lap combined with heat generated by laser irradiation of the AuNRs. In agreement, in vivo treatment with CM-ß-Lap-PEG-AuNRs and irradiation shows a histopathological recovery from nonmuscle invasive bladder cancer of most of the animals with only one cycle of application and irradiation. Such multifunctional platform is a promissing candidate for improved activated drug release and phototherapy.
