Journal: Scientific Reports

Article Title: Priming the body to receive the therapeutic agent to redefine treatment benefit/risk profile

doi: 10.1038/s41598-018-23140-9

Figure Lengend Snippet: liposomal nanoprimer biodistribution and acute toxicity evaluation. ( A ) Fluorescently labelled nanoprimer was intravenously injected alone on mice. Then, fluorescence acquisitions were performed on whole mice during 1 h using In Vivo Imaging system (IVIS). A massive hepatic accumulation was observed in the 10 min following injection. ( B ) Dose dependent accumulation of nanoprimer in liver, spleen, lungs, blood and carcass: Accumulation was measured by encapsulation of gold nanoparticles inside liposomes and quantification of gold in the different organs by inductively coupled plasma mass spectrometry 24 h after product injection (10 mL/kg) in mice (n = 5). Phospholipids amounts per g of organ (%ID/g) were extrapolated from Au quantified in organs reported to the ratio of Au/phospholipids of the injected nanoprimer solutions. Data are mean +/− SEM. ( C ) Serum concentration of aspartate aminotransferase (ASAT) and alanine aminotransaminase (ALAT) 1 or 7 days after last intravenous injection of 3 doses of 85 mM; 10 mL/kg nanoprimer (median, n = 4). Control mice received 3 doses of Hepes/NaCl (25 mM/145 mM) (median, n = 4). ( D ) Body weight evolution of mice during the 7 th days after the same treatment as in ( B ) (n = 4). ( E ) Liver histological observations performed 24 h after last injection of the 3 doses of nanoprimer or Hepes/NaCl. Square defines an example of mild grade mixed inflammation areas observed 24 h after last injection of maximized dose of nanoprimer. These areas remain only visible at minimal grade on 1 of 4 mice 7 days after last injection of nanoprimer. Scale bar: 250 µm.

Article Snippet: Then animals were immediately placed in dorsal recumbency in optical imaging system IVIS Spectrum of Perkin Elmer to perform 2D fluorescent acquisitions (ex: 745 nm; em: 820 nm) starting 1 min after nanoprimer injection, every minute during 1 h on whole body.

Techniques: Injection, Fluorescence, In Vivo Imaging, Encapsulation, Liposomes, Clinical Proteomics, Mass Spectrometry, Concentration Assay, Control

Journal: Scientific Reports

Article Title: Priming the body to receive the therapeutic agent to redefine treatment benefit/risk profile

doi: 10.1038/s41598-018-23140-9

Figure Lengend Snippet: Liposomal nanoprimer impact on nanomedicines blood bioavailability and anti-tumor efficacy on HT-29 tumor model. ( A ) PLGA nanoparticles were selected as this polymer is synthetic, biodegradable and used in drug delivery systems approved by FDA (EligardR, zoladexR) or in clinical trial (Bind-014) , . PLGA nanoparticles were intravenously injected alone on mice or after intravenous injection of liposomal nanoprimer with various time schedule (10 min, 7 and 24 h). Then, immediately after PLGA nanoparticles injection, fluorescence acquisitions were performed on whole mice during 1 h using In Vivo Imaging system (IVIS). Increased blood bioavailability for at least 1 hour is observed for the PLGA nanomedicine-based product administered 10 min after the liposomal nanoprimers when compared to the PLGA nanomedicine-based product alone. This enhanced blood availability is correlated with a lower accumulation of the product in the liver and spleen and without noticeable accumulation in other organs. The same experiment repeated with the PLGA nanoparticles injected 7 h or 24 h after the liposome as nanoprimers demonstrates that PLGA nanoparticles blood bioavailability is still increased by nanoprimers but in a lower extend since this effect decreases after 30 min highlighting transient MPS (liver and spleen) occupancy by the nanoprimers. (B) Kaplan-Meier diagram of camptothecin 11 (CTP11) liposomes +/− nanoprimer: mice were xenografted with HT-29 colorectal tumor model and randomized when the mean tumor volume reached 150 mm3. Mice were treated as follow: Control Hepes/NaCl (25 mM/145 mM) (orange curve, n = 5); nanoprimer alone 85 mM (black curve, n = 5); CPT11-liposomes 15 mg/kg alone (red curve, n = 8) and with nanoprimer 85 mM injected 10 min before each CPT11-liposomes injection (blue curve; n = 8). For all groups, intravenous injections were performed at days 0 and 6 (black arrows). Survival difference between the CPT11-liposomes alone and CPT11-liposomes with nanoprimer groups was evaluated with Mantel-Cox test, * p-value < 0.05.

Article Snippet: Then animals were immediately placed in dorsal recumbency in optical imaging system IVIS Spectrum of Perkin Elmer to perform 2D fluorescent acquisitions (ex: 745 nm; em: 820 nm) starting 1 min after nanoprimer injection, every minute during 1 h on whole body.

Techniques: Polymer, Injection, Fluorescence, In Vivo Imaging, Liposomes, Control