Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P00492 (
hypoxanthine-guanine phosphoribosyltransferase
)
2,385
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Purpose:
To further enhance the antitumor efficacy through targeted delivery, DTX loaded lipid-based-nanosuspensions (DTX-LNS) were prepared and functionalized by PEGylation or
NGR
modification to develop DSPE-PEG
2000
modified DTX-
LNS
(P-DTX-LNS) or DSPE-PEG
2000
-
NGR
modified DTX-
LNS
(N-DTX-LNS), respectively.
Methods:
Based on our previous work, functionalized DTX-
LNS
including P-DTX-
LNS
and N-DTX-
LNS
were prepared using thin-film hydration, and then characterized. Release behavior, stability in vitro, cytotoxicity and cellular uptake of functionalized
LNS
were observed. To demonstrate tumor targeting efficiency of functionalized DTX-
LNS
, in vivo real-time and ex vivo imaging study were conducted. Furthermore, therapeutic efficacy in vivo was evaluated in an H22-bearing mice model.
Results:
Functionalized DTX-
LNS
100-110 nm in diameter were successfully prepared and exhibited good stability under various conditions. In vitro release studies demonstrated that DTX was released from functionalized DTX-
LNS
steadily and reached approximately 95% at 48 hrs. Functionalized DTX-
LNS
showed dose-dependent cytotoxicity and time-dependent internalization in human hepatocellular liver carcinoma cells (HepG2) cells. In vivo real-time and ex vivo imaging results indicated that tumor targeting efficiencies of P-DiR-
LNS
and N-DiR-
LNS
were 29.9% and 34.3%, respectively. Moreover, evaluations of in vivo antitumor efficacy indicated that functionalized DTX-
LNS
effectively inhibited tumor growth with low toxicity.
Conclusion:
The functionalized
LNS
exhibited suitable particle size, nearly spherical structure, enough drug loading and great potentials for large-scale production. The results in vitro and in vivo demonstrated that functionalized
LNS
could realize tumor targeting and antitumor efficacy. Consequently, functionalized DTX-
LNS
could be expected to be used for tumor targeting therapy.
...
PMID:Functionalized docetaxel-loaded lipid-based-nanosuspensions to enhance antitumor efficacy in vivo. 3111 90
