Monoclonal Antibody 2C5-Modified Mixed Dendrimer Micelles for Tumor-Targeted Codelivery of Chemotherapeutics and siRNA
Pan J., Attia S. A., Subhan M. A., Filipczak N., Mendes L. P., Li X., Kishan Y. S. S., Torchilin V. P.
Molecular Pharmaceutics
Vol.17, Issue5, P. 1638-1647
Опубликовано: 2020
Тип ресурса: Статья
DOI:10.1021/acs.molpharmaceut.0c00075
Аннотация:
Targeted delivery of chemotherapeutics to tumors has the potential to reach a high dose at the tumor while minimizing systemic exposure. Incorporation of antibody within a micellar platform represents a drug delivery system for tumor-targeted delivery of antitumor agents. Such modified immunomicelles can result in an increased accumulation of antitumor agents and enhanced cytotoxicity toward cancer cells. Here, mixed dendrimer micelles (MDM) composed of PEG2k-DOPE-conjugated generation 4 polyamidoamine dendrimer G4-PAMAM-PEG2k-DOPE and PEG5k-DOPE were coloaded with doxorubicin and siMDR-1. This formulation was further modified with monoclonal antibodies 2C5 with nucleosome-restricted specificity that effectively recognized cancer cells via the cell-surface-bound nucleosomes. Micelles with attached 2C5 antibodies significantly enhanced cellular association and tumor killing in both monolayer and spheroid tumor models as well as in vivo in experimental animals compared to the nontargeted
Ключевые слова:
chemotherapy; combination delivery; micelle; mixed dendrimer micelles (MDM); monoclonal antibody 2C5; multidrug resistance; polyamidoamine (PAMAM); siRNA delivery
4 polyamidoamine; dendrimer; doxorubicin; monoclonal antibody; monoclonal antibody 2c5; polyamidoamine; small interfering RNA; unclassified drug; Article; cancer cell; human; human cell; micelle; nucleosome; priority journal
Язык текста: Английский
ISSN: 1543-8392
Pan J.
Attia S. A.
Subhan M. A.
Filipczak N.
Mendes L. P.
Li X.
Kishan Y. S. S. Yalamarty S.S.
Torchilin V. P. Vladimir Petrovich 1946-
Пан Й.
Аттиа С. А.
Субхан М. А.
Филипcзак Н.
Мендес Л. П.
Ли Х.
Кишан Y. С. С. Яламартy С.С.
Торчилин В. П. Владимир Петрович 1946-
Monoclonal Antibody 2C5-Modified Mixed Dendrimer Micelles for Tumor-Targeted Codelivery of Chemotherapeutics and siRNA
Текст визуальный непосредственный
Molecular Pharmaceutics
American Chemical Society
Vol.17, Issue5 P. 1638-1647
2020
Статья
chemotherapy combination delivery micelle mixed dendrimer micelles (MDM) monoclonal antibody 2C5 multidrug resistance polyamidoamine (PAMAM) siRNA delivery
4 polyamidoamine dendrimer doxorubicin monoclonal antibody monoclonal antibody 2c5 polyamidoamine small interfering RNA unclassified drug Article cancer cell human human cell micelle nucleosome priority journal
Targeted delivery of chemotherapeutics to tumors has the potential to reach a high dose at the tumor while minimizing systemic exposure. Incorporation of antibody within a micellar platform represents a drug delivery system for tumor-targeted delivery of antitumor agents. Such modified immunomicelles can result in an increased accumulation of antitumor agents and enhanced cytotoxicity toward cancer cells. Here, mixed dendrimer micelles (MDM) composed of PEG2k-DOPE-conjugated generation 4 polyamidoamine dendrimer G4-PAMAM-PEG2k-DOPE and PEG5k-DOPE were coloaded with doxorubicin and siMDR-1. This formulation was further modified with monoclonal antibodies 2C5 with nucleosome-restricted specificity that effectively recognized cancer cells via the cell-surface-bound nucleosomes. Micelles with attached 2C5 antibodies significantly enhanced cellular association and tumor killing in both monolayer and spheroid tumor models as well as in vivo in experimental animals compared to the nontargeted