M. Huang, et al.
Bioorganic&MedicinalChemistryLetters30(2020)127151
accumulation in tumor region from 2 h to 16 h after a systemic ad-
ministration. The fluorescence signal of all liposomes was time depen-
dent, showing weak intensity at tumor site at 2 h after injection, the
maximum intensity at 12 h post injection, and decreasing intensity from
16 h to 24 h after injection (Fig. 6). The mice were sacrificed at pre-
determined time points, and the tumor tissues, hearts, livers, spleens,
lungs, and kidneys were harvested and imaged. Ex vivo images of the
tumor tissues and other organs were shown in Fig. 6B and D, respec-
tissues was shown in Fig. 6C, with the highest intensity by DID-Bio-Glu-
Lip, 2.23-fold higher than that of Lip at 12 h after injection. From 2 h to
24 h after injection, strong fluorescence signal of different liposomes
was shown in the liver and in part of the spleen, with no apparent signal
in hearts, lungs, and kidneys. These in vivo imaging results suggested
that biotin and glucose on the surface of liposomes equip the liposomes
with the breast tumor dual-targeting delivery ability. These findings
were consistent with those of in vitro cellular uptake. As the compounds
encapsulated within liposomes would not change the targeting prop-
erties of liposomes, it is reasonably to believe that the targeting and
time related accumulation in the breast tumor of other compounds
loaded in Bio-Glu-Lip are similar to DID loaded in the same liposome
vectors. Furthermore, we had analyzed the pharmacokinetic para-
meters of free PTX, PTX-Lip, PTX-Glu-Lip, and PTX-Bio-Lip in our
previous studies18,19; the plasma PTX concentration–time profiles were
shown and the pharmacokinetic parameters of PTX from different for-
mulations were summarized previously. The results showed that the
ligands modified liposomes could significantly enhance the con-
centration–time profile (AUC0-t) of paclitaxel within 24 h, the AUC0-t of
Acknowledgments
This work was supported by the National Natural Science
Foundation of China (No. 81573286, No. 81773577, No. 21472130,
and No. 81803420), the Sichuan Science and Technology Program
(2018JY0537).
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://
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Declaration of Competing Interest
posomes for delivery to brain in vivo: biodistribution and transfection. J Control
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influ-
ence the work reported in this paper.
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