Golnaz Mardani - Academia.edu (original) (raw)
Papers by Golnaz Mardani
Journal of Solid Tumors, Aug 10, 2015
Peptides, 2017
HIGHLIGHTSCell penetrating peptides (CPPs) promote the delivery of therapeutic proteins or peptid... more HIGHLIGHTSCell penetrating peptides (CPPs) promote the delivery of therapeutic proteins or peptides into live cells.Noncovalent complex formation between proteins and CPPs could overcome some delivery limitations.Successful delivery of proteins mainly depends on their physicochemical properties.Effective protein transduction domains can enhance the potency of protein therapeutics. ABSTRACT The failure of proteins to penetrate mammalian cells or target tumor cells restricts their value as therapeutic tools in a variety of diseases such as cancers. Recently, protein transduction domains (PTDs) or cell penetrating peptides (CPPs) have been shown to promote the delivery of therapeutic proteins or peptides into live cells. The successful delivery of proteins mainly depends on their physicochemical properties. Although, linear cell penetrating peptides are one of the most effective delivery vehicles; but currently, cyclic CPPs has been developed to potently transport bioactive full‐length proteins into cells. Up to now, several small protein transduction domains from viral proteins including Tat or VP22 could be fused to other peptides or proteins to entry them in various cell types at a dose‐dependent approach. A major disadvantage of PTD‐fusion proteins is primary uptake into endosomal vesicles leading to inefficient release of the fusion proteins into the cytosol. Recently, non‐covalent complex formation (Chariot) between proteins and CPPs has attracted a special interest to overcome some delivery limitations (e.g., toxicity). Many preclinical and clinical trials of CPP‐based delivery are currently under evaluation. Generally, development of more efficient protein transduction domains would significantly increase the potency of protein therapeutics. Moreover, the synergistic or combined effects of CPPs with other delivery systems for protein/peptide drug delivery would promote their therapeutic effects in cancer and other diseases. In this review, we will describe the functions and implications of CPPs for delivering the therapeutic proteins or peptides in preclinical and clinical studies.
IUBMB Life, 2016
Two human papillomavirus (HPV) viral oncoproteins, E6 and E7 represent ideal targets for developm... more Two human papillomavirus (HPV) viral oncoproteins, E6 and E7 represent ideal targets for development of a therapeutic HPV vaccine. It is important to reduce the rate of HPVassociated malignancies through improvement of vaccine modalities. In this study, we used a short amphipathic peptide carrier, Pep-1, for delivery of the full-length HPV16 E7 protein into mammalian cells and evaluated immune responses and protective effects of different formulations in C57BL/6 tumor mice model. Our results showed that the complexes of E7/ Pep-1 protein form stable nanoparticles through noncovalent binding with an average size of 120 to 250 nm. The efficient delivery of E7 protein by Pep-1 at molar ratio of 1:20 was detected in HEK-293T cell line for 1 h and 3 h posttransfection. Immunization with E7/Pep-1 nanoparticles at a ratio of 1:20 induced a higher Th1 cellular immune response with the predominant IgG2a and IFN-c levels than those induced by E7 protein in a murine tumor model. These data suggest that Pep-1 peptide would indicate promising applications for improvement of HPV therapeutic vaccines.
Journal of Solid Tumors, 2015
High-risk genotypes of human papillomavirus (HPV) are associated with genital cancers especially ... more High-risk genotypes of human papillomavirus (HPV) are associated with genital cancers especially cervical cancer. United State Food and Drug Administration (USFDA) has recently licensed two first-generation prophylactic vaccines (i.e., Gardasil and Cervarix), for control of HPV 16 and 18 infections. Both vaccines are able to generate neutralizing antibodies against major capsid protein L1 assembled as virus-like particles (VLPs). To enhance protection against other HPV genotypes, second-generation vaccines are underway. A HPV L1-based nonavalent vaccine showed is potent and safe in prevention of precancerous lesions associated with HPV types 16/18/31/33/45/52/58, as well as anogenital warts associated with HPV types 6/11. This vaccine is in the advanced stage of phase III clinical trials. Other second-generation vaccines were based on L1-pentameric subunits and also the minor capsid protein L2 that have shown to be effective in preclinical studies. The L2 protein co-assembles with the L1 protein for VLP formation increasing virion aggregation. This mini-review describes two vaccination strategies including first-generation and second-generation vaccines against HPV infections.
High-risk genotypes of human papillomavirus (HPV) are associated with genital cancers especially ... more High-risk genotypes of human papillomavirus (HPV) are associated with genital cancers especially cervical cancer. United State Food and Drug Administration (USFDA) has recently licensed two first-generation prophylactic vaccines (i.e., Gardasil and Cervarix), for control of HPV 16 and 18 infections. Both vaccines are able to generate neutralizing antibodies against major capsid protein L1 assembled as virus-like particles (VLPs). To enhance protection against other HPV genotypes, second-generation vaccines are underway. A HPV L1-based nonavalent vaccine showed is potent and safe in prevention of precancerous lesions associated with HPV types 16/18/31/33/45/52/58, as well as anogenital warts associated with HPV types 6/11. This vaccine is in the advanced stage of phase III clinical trials. Other second-generation vaccines were based on L1-pentameric subunits and also the minor capsid protein L2 that have shown to be effective in preclinical studies. The L2 protein co-assembles with t...
Peptides, 2017
HIGHLIGHTSCell penetrating peptides (CPPs) promote the delivery of therapeutic proteins or peptid... more HIGHLIGHTSCell penetrating peptides (CPPs) promote the delivery of therapeutic proteins or peptides into live cells.Noncovalent complex formation between proteins and CPPs could overcome some delivery limitations.Successful delivery of proteins mainly depends on their physicochemical properties.Effective protein transduction domains can enhance the potency of protein therapeutics. ABSTRACT The failure of proteins to penetrate mammalian cells or target tumor cells restricts their value as therapeutic tools in a variety of diseases such as cancers. Recently, protein transduction domains (PTDs) or cell penetrating peptides (CPPs) have been shown to promote the delivery of therapeutic proteins or peptides into live cells. The successful delivery of proteins mainly depends on their physicochemical properties. Although, linear cell penetrating peptides are one of the most effective delivery vehicles; but currently, cyclic CPPs has been developed to potently transport bioactive full‐length proteins into cells. Up to now, several small protein transduction domains from viral proteins including Tat or VP22 could be fused to other peptides or proteins to entry them in various cell types at a dose‐dependent approach. A major disadvantage of PTD‐fusion proteins is primary uptake into endosomal vesicles leading to inefficient release of the fusion proteins into the cytosol. Recently, non‐covalent complex formation (Chariot) between proteins and CPPs has attracted a special interest to overcome some delivery limitations (e.g., toxicity). Many preclinical and clinical trials of CPP‐based delivery are currently under evaluation. Generally, development of more efficient protein transduction domains would significantly increase the potency of protein therapeutics. Moreover, the synergistic or combined effects of CPPs with other delivery systems for protein/peptide drug delivery would promote their therapeutic effects in cancer and other diseases. In this review, we will describe the functions and implications of CPPs for delivering the therapeutic proteins or peptides in preclinical and clinical studies.
Journal of Solid Tumors, Aug 10, 2015
Peptides, 2017
HIGHLIGHTSCell penetrating peptides (CPPs) promote the delivery of therapeutic proteins or peptid... more HIGHLIGHTSCell penetrating peptides (CPPs) promote the delivery of therapeutic proteins or peptides into live cells.Noncovalent complex formation between proteins and CPPs could overcome some delivery limitations.Successful delivery of proteins mainly depends on their physicochemical properties.Effective protein transduction domains can enhance the potency of protein therapeutics. ABSTRACT The failure of proteins to penetrate mammalian cells or target tumor cells restricts their value as therapeutic tools in a variety of diseases such as cancers. Recently, protein transduction domains (PTDs) or cell penetrating peptides (CPPs) have been shown to promote the delivery of therapeutic proteins or peptides into live cells. The successful delivery of proteins mainly depends on their physicochemical properties. Although, linear cell penetrating peptides are one of the most effective delivery vehicles; but currently, cyclic CPPs has been developed to potently transport bioactive full‐length proteins into cells. Up to now, several small protein transduction domains from viral proteins including Tat or VP22 could be fused to other peptides or proteins to entry them in various cell types at a dose‐dependent approach. A major disadvantage of PTD‐fusion proteins is primary uptake into endosomal vesicles leading to inefficient release of the fusion proteins into the cytosol. Recently, non‐covalent complex formation (Chariot) between proteins and CPPs has attracted a special interest to overcome some delivery limitations (e.g., toxicity). Many preclinical and clinical trials of CPP‐based delivery are currently under evaluation. Generally, development of more efficient protein transduction domains would significantly increase the potency of protein therapeutics. Moreover, the synergistic or combined effects of CPPs with other delivery systems for protein/peptide drug delivery would promote their therapeutic effects in cancer and other diseases. In this review, we will describe the functions and implications of CPPs for delivering the therapeutic proteins or peptides in preclinical and clinical studies.
IUBMB Life, 2016
Two human papillomavirus (HPV) viral oncoproteins, E6 and E7 represent ideal targets for developm... more Two human papillomavirus (HPV) viral oncoproteins, E6 and E7 represent ideal targets for development of a therapeutic HPV vaccine. It is important to reduce the rate of HPVassociated malignancies through improvement of vaccine modalities. In this study, we used a short amphipathic peptide carrier, Pep-1, for delivery of the full-length HPV16 E7 protein into mammalian cells and evaluated immune responses and protective effects of different formulations in C57BL/6 tumor mice model. Our results showed that the complexes of E7/ Pep-1 protein form stable nanoparticles through noncovalent binding with an average size of 120 to 250 nm. The efficient delivery of E7 protein by Pep-1 at molar ratio of 1:20 was detected in HEK-293T cell line for 1 h and 3 h posttransfection. Immunization with E7/Pep-1 nanoparticles at a ratio of 1:20 induced a higher Th1 cellular immune response with the predominant IgG2a and IFN-c levels than those induced by E7 protein in a murine tumor model. These data suggest that Pep-1 peptide would indicate promising applications for improvement of HPV therapeutic vaccines.
Journal of Solid Tumors, 2015
High-risk genotypes of human papillomavirus (HPV) are associated with genital cancers especially ... more High-risk genotypes of human papillomavirus (HPV) are associated with genital cancers especially cervical cancer. United State Food and Drug Administration (USFDA) has recently licensed two first-generation prophylactic vaccines (i.e., Gardasil and Cervarix), for control of HPV 16 and 18 infections. Both vaccines are able to generate neutralizing antibodies against major capsid protein L1 assembled as virus-like particles (VLPs). To enhance protection against other HPV genotypes, second-generation vaccines are underway. A HPV L1-based nonavalent vaccine showed is potent and safe in prevention of precancerous lesions associated with HPV types 16/18/31/33/45/52/58, as well as anogenital warts associated with HPV types 6/11. This vaccine is in the advanced stage of phase III clinical trials. Other second-generation vaccines were based on L1-pentameric subunits and also the minor capsid protein L2 that have shown to be effective in preclinical studies. The L2 protein co-assembles with the L1 protein for VLP formation increasing virion aggregation. This mini-review describes two vaccination strategies including first-generation and second-generation vaccines against HPV infections.
High-risk genotypes of human papillomavirus (HPV) are associated with genital cancers especially ... more High-risk genotypes of human papillomavirus (HPV) are associated with genital cancers especially cervical cancer. United State Food and Drug Administration (USFDA) has recently licensed two first-generation prophylactic vaccines (i.e., Gardasil and Cervarix), for control of HPV 16 and 18 infections. Both vaccines are able to generate neutralizing antibodies against major capsid protein L1 assembled as virus-like particles (VLPs). To enhance protection against other HPV genotypes, second-generation vaccines are underway. A HPV L1-based nonavalent vaccine showed is potent and safe in prevention of precancerous lesions associated with HPV types 16/18/31/33/45/52/58, as well as anogenital warts associated with HPV types 6/11. This vaccine is in the advanced stage of phase III clinical trials. Other second-generation vaccines were based on L1-pentameric subunits and also the minor capsid protein L2 that have shown to be effective in preclinical studies. The L2 protein co-assembles with t...
Peptides, 2017
HIGHLIGHTSCell penetrating peptides (CPPs) promote the delivery of therapeutic proteins or peptid... more HIGHLIGHTSCell penetrating peptides (CPPs) promote the delivery of therapeutic proteins or peptides into live cells.Noncovalent complex formation between proteins and CPPs could overcome some delivery limitations.Successful delivery of proteins mainly depends on their physicochemical properties.Effective protein transduction domains can enhance the potency of protein therapeutics. ABSTRACT The failure of proteins to penetrate mammalian cells or target tumor cells restricts their value as therapeutic tools in a variety of diseases such as cancers. Recently, protein transduction domains (PTDs) or cell penetrating peptides (CPPs) have been shown to promote the delivery of therapeutic proteins or peptides into live cells. The successful delivery of proteins mainly depends on their physicochemical properties. Although, linear cell penetrating peptides are one of the most effective delivery vehicles; but currently, cyclic CPPs has been developed to potently transport bioactive full‐length proteins into cells. Up to now, several small protein transduction domains from viral proteins including Tat or VP22 could be fused to other peptides or proteins to entry them in various cell types at a dose‐dependent approach. A major disadvantage of PTD‐fusion proteins is primary uptake into endosomal vesicles leading to inefficient release of the fusion proteins into the cytosol. Recently, non‐covalent complex formation (Chariot) between proteins and CPPs has attracted a special interest to overcome some delivery limitations (e.g., toxicity). Many preclinical and clinical trials of CPP‐based delivery are currently under evaluation. Generally, development of more efficient protein transduction domains would significantly increase the potency of protein therapeutics. Moreover, the synergistic or combined effects of CPPs with other delivery systems for protein/peptide drug delivery would promote their therapeutic effects in cancer and other diseases. In this review, we will describe the functions and implications of CPPs for delivering the therapeutic proteins or peptides in preclinical and clinical studies.