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- Principal physicochemical methods used to characterize dendrimer molecule complexes used as genetic therapy agents, nanovaccines or drug carriersPublication . Rolando Alberto, Rodriguez Fonseca; Rodrigues, João; Muñoz-Fernández, María de los Angeles; Martínez Muñoz, Alberto; Fragoso Vázquez, Manuel Jonathan; Correa-Basurto, JoséNanomedicine is the application of nanotechnology to medicine. This field is related to the study of nanodevices and nanomaterials applied to various medical uses, such as in improving the pharmacological properties of different molecules. Dendrimers are synthetic nanoparticles whose physicochemical properties vary according to their chemical structure. These molecules have been extensively investigated as drug nanocarriers to improve drug solubility and as sustained-release systems. New therapies such as gene therapy and the development of nanovaccines can be improved by the use of dendrimers. The biophysical and physicochemical characterization of nucleic acid/peptide-dendrimer complexes is crucial to identify their functional properties prior to biological evaluation. In that sense, it is necessary to first identify whether the peptide-dendrimer or nucleic aciddendrimer complexes can be formed and whether the complex can dissociate under the appropriate conditions at the target cells. In addition, biophysical and physicochemical characterization is required to determine how long the complexes remain stable, what proportion of peptide or nucleic acid is required to form the complex or saturate the dendrimer, and the size of the complex formed. In this review, we present the latest information on characterization systems for dendrimer-nucleic acid, dendrimer-peptide and dendrimer-drug complexes with several biotechnological and pharmacological applications.
- In silico search, chemical characterization and immunogenic evaluation of amino-terminated G4-PAMAM-HIV peptide complexes using three-dimensional models of the HIV-1 gp120 proteinPublication . Rodríguez-Fonseca, Rolando Alberto; Bello, Martiniano; Muñoz-Fernández, María Ángeles de los; Luis Jiménez, José; Rojas-Hernández, Saúl; Fragoso-Vázquez, M.J.; Gutiérrez-Sánchez, Mara; Rodrigues, João; Cayetano-Castro, N.; Borja-Urby, R.; Rodríguez-Cortés, Octavio; García-Machorro, Jazmín; Correa-Basurto, JoséPeptide epitopes have been widely used to develop synthetic vaccines and immunotherapies. However, peptide epitopes may exhibit poor absorption or immunogenicity due to their low molecular weights. Conversely, fourth-generation polyamidoamine (G4-PAMAM) dendrimers are nonimmunogenic and relatively nontoxic synthetic nanoparticles that have been used as adjuvants and nanocarriers of small peptides and to improve nasal absorption. Based on this information, we hypothesized that the combination of intranasal immunization and G4-PAMAM dendrimers would be useful for enhancing the antibody responses of HIV-1 gp120 peptide epitopes. Therefore, we first used structural data, peptide epitope predictors and docking and MD simulations on MHC-II to identify two peptide epitopes on the CD4 binding site of HIV-1 gp120. The formation of G4-PAMAM-peptide complexes was evaluated in silico (molecular docking studies using different G4-PAMAM conformations retrieved from MD simulations as well as the MMGBSA approach) and validated experimentally (electrophoresis, 1H NMR and cryo-TEM). Next, the G4-PAMAM dendrimer-peptide complexes were administered intranasally to groups of female BALB/cJ mice. The results showed that both peptides were immunogenic at the systemic and mucosal levels (nasal and vaginal), and G4-PAMAM dendrimer-peptide complexes improved IgG and IgA responses in serum and nasal washes. Thus, G4-PAMAM dendrimers have potential for use as adjuvants and nanocarriers of peptides.