Pharmacokinetics of the ¹¹¹In-doxorubicin liposomes in GBM-bearing mice determined by micro-SPECT/CT.

<p>Tumor-to-contralateral brain ratios for ¹¹¹In-doxorubicin liposomes in the GBM-bearing mice were derived from the dynamic micro-SPECT/CT images after intravenous injection followed by sonication or nonsonication. * and # denote a significant difference compared with AP-1 Lipo-Dox and Lipo-Dox plus FUS, respectively (* and #, <i>p</i><0.05). + and ‡ denote a significant difference compared with Lipo-Dox and AP-1 Lipo-Dox, respectively (+ and ‡, <i>p</i><0.05).</p

Twelve days after tumor implantation, three mice each form the control group, the targeted Lipo-Dox without pulsed FUS group, and the targeted Lipo-Dox with pulsed FUS group were sacrificed.

<p>Sections of the tumors were collected for hematoxylin and eosin histological examination. (scale bar = 500 µm [a-c]; scale bar  = 100 µm [d-f]).</p

The composition and properties of prepared Lipo-Dox and AP-1 Lipo-Dox.

<p>The composition and properties of prepared Lipo-Dox and AP-1 Lipo-Dox.</p

Systemic toxicity of AP-1 Lipo-Dox in tumor-bearing mice.

<p>(a) Serum chemistry of mice treated with AP-1 Lipo-Dox without or with sonication. The control tumor group received phosphate-buffered saline. Mice received treatments on days 5 and 9 after implantation. All animals were sacrificed for toxicity evaluation on day 12 after implantation. GOT = glutamic oxaloacetic transaminase, GPT = glutamic pyruvic transaminase, BUN = blood-urea nitrogen; ^*<i>p</i><0.05, ^**<i>p</i><0.01. (b) Mean body weights (relative to day 5) of tumor-bearing mice treated with AP-1 Lipo-Dox with or without sonication.</p

Schematic diagram for the ¹¹¹In-AP-1 Lipo-Dox.

<p>Liposomes were prepared containing maleimide-functional polyethylene glycol chains. The maleimide was used to attach the AP-1 peptide through the thiol group on a cystine. ¹¹¹In label was introduced into the liposomes. Therapeutic liposomes were loaded with Dox. DSPE-PEG2000 = 1,2-distearoyl-<i>sn</i>-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000], MAL = maleimide.</p

Schematic diagram of the experimental setup for blood-brain barrier opening.

<p>The positioner was also mounted on a stereotaxic apparatus. PE, polyurethane.</p

Body weight loss of the C26/tk-luc colon carcinoma-bearing mice after treatment with various liposomal drugs.

<p>The mice bearing large tumor (<i>n</i> = 9 for each group, A) and those bearing small tumor (<i>n</i> = 6 for each group, B) were injected intravenously with NanoX (•), InNanoX (▽), NanoVNB (▪) or InVNBL (◊) at 0, 7, and 14 days after first injection (arrow; three injections total). The zero time point indicates the initiation of therapy. Data were expressed as mean ± S.E.M.</p

Relationship between tumor uptake (%ID/g) and tumor mass at 48 h after administration of InVNBL in mice bearing differently sized C26/tk-luc tumors.

<p>Relationship between tumor uptake (%ID/g) and tumor mass at 48 h after administration of InVNBL in mice bearing differently sized C26/tk-luc tumors.</p

Whole-body scintigraphic images of the C26/tk-luc colon carcinoma-bearing mice at designated time points during the period of treatment with InNanoX and InVNBL.

<p>The scintigraphic imaging was performed for 20 min at 48 h after drugs administration (37 MBq/100 µL per injection) and at 8 days after the last course of treatment. The mice were anesthetized with 1∼3% isoflurane for all imaging. Tumor nodules are indicated by red arrows.</p

<i>In vivo</i> BLI of the C26/tk-luc colon carcinoma-bearing mice after treatment with various liposomal drugs.

<p>The large-tumor mice receiving various liposomal drugs were intraperitoneally injected with 150 mg/kg d-luciferin 15 min prior to image acquisition at designated time points. The photons emitted from the mice (positioned prone) were acquired for 1 minute. The mice were anesthetized with 1∼3% isoflurane while conducting imaging.</p