Ovarian cancer is particularly aggressive once it has metastasized to the abdominal cavity (stage III). Intraperitoneal (IP) as compared to intravenous (IV) administration of chemotherapy improves survival for stage III ovarian cancer, demonstrating that concentrating chemotherapy at tumor sites has therapeutic benefit; unfortunately, IP therapy also increases toxic side effects, thus preventing its completion in many patients. The ability to target chemotherapy selectively to ovarian tumors while sparing normal tissue would improve efficacy and decrease toxicities. We have previously shown that tumor-tropic neural stem cells (NSCs) dramatically improve the intratumoral distribution of nanoparticles (NPs) when given intracerebrally near an orthotopic brain tumor or into a flank xenograft tumor. Here we show that NPs either conjugated to the surface of NSCs or loaded within the cells are selectively delivered to and distributed within ovarian tumors in the abdominal cavity following IP injection, with no evidence of localization to normal tissue. IP administration is significantly more effective than IV administration and NPs carried by NSCs show substantially deeper penetration into tumors than free NPs. The NSC/NPs target and localize to ovarian tumors within 1 hr of administration. Pt-loaded silica NPs (SiNP[Pt]) were developed that can be transported in NSCs and it was found that NSC delivery of SiNP[Pt] (NSC/SiNP[Pt]) results in higher levels of Pt in tumors as compared to free drug or SiNP[Pt]. To the best of our knowledge, this work represents the first demonstration that cells given IP can target the delivery of drug-loaded NPs.
A novel one-pot synthesis method to prepare gold nanorods of different aspect ratios using radiolysis is presented. The gold nanorods are synthesized by radiolytic reduction of Au III complexes in a micellar solution formed by a mixture of cationic surfactants (cetyltrimethylammonium bromide and tetraoctylammonium bromide) and in the presence of acetone and silver ions. The mechanisms of reduction of gold complexes and formation of the nanorods are discussed. The nanorods can be trapped in a poly(vinyl alcohol) gel formed under irradiation. The UV-visible absorption spectra of nanorod solutions are compared with calculations performed by using the discrete dipole approximation method, underlying the effect of the rod aspect ratio distribution.
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