Cancer-cell-specific induction of apoptosis using mesoporous silica nanoparticles as drug-delivery vectors.
Targeted delivery of the chemotherapeutic agent methotrexate (MTX) to cancer cells using poly(ethyleneimine)-functionalized mesoporous silica particles as drug-delivery vectors is reported. Due to its high affinity for folate receptors, the expression of which is elevated in cancer cells, MTX serves as both a targeting ligand and a cytotoxic agent. Enhanced cancer-cell apoptosis (programmed cell death) relative to free MTX is thus observed at particle concentrations where nonspecific MTX-induced apoptosis is not observed in the nontargeted healthy cell line, while corresponding amounts of free drug affect both cell lines equally. The particles remain compartmentalized in endo-/lysosomes during the time of observation (up to 72 h), while the drug is released from the particle only upon cell entry, thereby inducing selective apoptosis in the target cells. As MTX is mainly attached to the particle surface, an additional advantage is that the presented carrier design allows for adsorption (loading) of additional drugs into the pore network for therapies based on a combination of drugs.
Rosenholm
Jessica M
JM
Center for Functional Materials, Department of Physical Chemistry, Abo Akademi University, Porthansgatan 3-5, 2500 Turku, Finland.
Peuhu
Emilia
E
Bate-Eya
Laurel Tabe
LT
Eriksson
John E
JE
Sahlgren
Cecilia
C
Lindén
Mika
M
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects*; D004337:Drug Carriers / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008422:Materials Testing; D008727:Methotrexate / Q000008:administration & dosage*; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use*; D012822:Silicon Dioxide / Q000737:chemistry*
D000970:Antineoplastic Agents; D004337:Drug Carriers; D012822:Silicon Dioxide; D008727:Methotrexate