Synergistic targeting of cell membrane, cytoplasm, and nucleus of cancer cells using rod-shaped nanoparticles.
Design of carriers for effective delivery and targeting of drugs to cellular and subcellular compartments is an unmet need in medicine. Here, we report pure drug nanoparticles comprising camptothecin (CPT), trastuzumab (TTZ), and doxorubicin (DOX) to enable cell-specific interactions, subcellular accumulation, and growth inhibition of breast cancer cells. CPT is formulated in the form of nanorods which are coated with TTZ. DOX is encapsulated in the TTZ corona around the CPT nanoparticle. Our results show that TTZ/DOX-coated CPT nanorods exhibit cell-specific internalization in BT-474 breast cancer cells, after which TTZ is recycled to the plasma membrane, leaving CPT nanorods in the perinuclear region and delivering DOX into the nucleus of the cells. The effects of CPT-TTZ-DOX nanoparticles on growth inhibition are synergistic (combination index = 0.17 ± 0.03) showing 10-10 000-fold lower inhibitory concentrations (IC50) compared to those of individual drugs. The design of antibody-targeted pure drug nanoparticles offers a promising design strategy to facilitate intracellular delivery and therapeutic efficiency of anticancer drugs.
Department of Chemical Engineering, Center for Bioengineering, University of California , Santa Barbara, Santa Barbara, California 93106, United States.
Sutapa
S
Barua
Samir
S
Mitragotri
D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000648:ultrastructure; D002166:Camptothecin / Q000008:administration & dosage; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D043942:Nanotubes / Q000737:chemistry; D000068878:Trastuzumab
D061067:Antibodies, Monoclonal, Humanized; D004337:Drug Carriers; D004317:Doxorubicin; D000068878:Trastuzumab; D002166:Camptothecin