Theranostic etoposide phosphate/indium nanoparticles for cancer therapy and imaging.
Etoposide phosphate (EP), a water-soluble anticancer prodrug, is widely used for treatment of many cancers. After administration it is rapidly converted to etoposide, its parent compound, which exhibits anticancer activity. Difficulty in parenteral administration necessitates the development of a suitable nanoparticle delivery system for EP. Here we have used indium both as a carrier to deliver etoposide phosphate to tumor cells and as a SPECT imaging agent through incorporation of (111)In. Etoposide phosphate was successfully encapsulated together with indium in nanoparticles, and exhibited dose dependent cytotoxicity and induction of apoptosis in cultured H460 cancer cells via G2/M cell cycle arrest. In a mouse xenograft lung cancer model, etoposide phosphate/indium nanoparticles induce tumor cell apoptosis, leading to significant enhancement of tumor growth inhibition compared to the free drug.
Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Ramishetti
R
Srinivas
UNC and NCSU Joint Department of Biomedical Engineering, Chapel Hill, NC 27599.
Andrew
A
Satterlee
Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Yuhua
Y
Wang
Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Yuan
Y
Zhang
Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Yongjun
Y
Wang
Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.|UNC and NCSU Joint Department of Biomedical Engineering, Chapel Hill, NC 27599.
Leaf
L
Huang
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004337:Drug Carriers; D005047:Etoposide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D007204:Indium / Q000737:chemistry / Q000494:pharmacology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000494:pharmacology; D000068936:Theranostic Nanomedicine / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
D004337:Drug Carriers; D009943:Organophosphorus Compounds; D007204:Indium; C061400:etoposide phosphate; D005047:Etoposide