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Our results suggest that radionuclide and chemoradiotherapeutic passive targeting delivery, using nanoliposomes as the carrier, is feasible and promising in systemic-targeted radionuclide therapy.

The effects of dehydroepiandrosterone (5-androsten-3␤-ol-17-one; DHEA) and related steroids on the capsaicin receptormediated current were studied in acutely dissociated rat dorsal root ganglion neurons using the whole-cell voltage-clamp technique. DHEA rapidly and reversibly inhibited the capsaicininduced current in a concentration-dependent manner, with an EC 50 of 6.7 M and a maximal inhibition of 100%. DHEA increased the capsaicin EC 50 with little effect on the capsaicin maximal response, suggesting that the blocking action of DHEA is competitive. Neither the capsaicin response nor inhibition of the capsaicin response by extracellularly applied DHEA was significantly affected by inclusion of a saturating concentration of DHEA in the electrode buffer, arguing that DHEA acted at the extracellular surface of the membrane. Moreover, DHEA did not act through protein phosphatases to inhibit the capsaicin-induced current. Furthermore, the stereoisomer of DHEA, 5-androsten-3␣-ol-17-one, failed to inhibit the capsaicin-induced current, producing instead a potentiating effect on the capsaicin response, demonstrating that the interaction of steroids with the capsaicin receptor is stereospecific. The inhibitory action of DHEA on the capsaicin-induced current may provide a basis for reducing capsaicin receptor-mediated nociception.

Liposomes can selectively target cancer sites and carry payloads, thereby improving diagnostic and therapeutic effectiveness and reducing toxicity. To evaluate therapeutic strategies, it is essential to use animal models reflecting important safety aspects before clinical application. The objective of this study was to investigate acute radiotoxicity of ¹⁸⁸Re-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomes (¹⁸⁸Re-BMEDA-liposome) in Sprague-Dawley rats. Rats were administered with ¹⁸⁸Re-BMEDA-liposome, normal saline as blank or non-radioactive liposome as vehicle control via intravenous injection and observed for 14 days. Examinations were conducted with respect to mortality, clinical signs, food consumption, body weight and hematological and biochemical analyses. In addition, gross necropsy, histopathological examinations and cytogenetic analyses were also performed. None of the rats died and no clinical sign was observed during the 14-day study period. Rats administered with ¹⁸⁸Re-BMEDA-liposome at dosage of 185 MBq displayed a significant weight loss compared with the control from study day (SD) 1 to SD 4, and the white blood cell count reduced to 5-10% of initial value (female: 18.55 ± 6.58 to 0.73 ± 0.26 x 10³  µl⁻¹; male: 14.52 ± 5.12 to 1.43 ± 0.54 x 10³  µl⁻¹) 7 days-post injection, but were found to have recovered on SD 15. There were no significant differences in biochemical parameters and histopathological assessments between the ¹⁸⁸Re-BMEDA-liposome-treated and control groups. The frequencies of dicentric chromosomes were associated with dosage of ¹⁸⁸Re-BMEDA-liposome. The information generated from this study on acute toxicity will serve as a safety reference for further subacute toxicity study in rats and human clinical trials.

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