Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.1 (ACS)
 78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemotherapy outcomes for the treatment of glioma remain unsatisfied due to the inefficient drug transport across BBB/BBTB and poor drug accumulation in the tumor site. Nanocarriers functionalized with different targeting ligands are considered as one of the most promising alternatives. However, few studies were reported to compare the targeting efficiency of the ligands and develop nanoparticles to realize BBB/BBTB crossing and brain tumor targeting simultaneously. In this study, six peptide-based ligands (Angiopep-2, T7, Peptide-22, c(RGDfK), D-SP5 and Pep-1), widely used for brain delivery, were selected to decorate liposomes, respectively, so as to compare their targeting ability to BBB or BBTB. Based on the in vitro cellular uptake results on BCECs and HUVECs, Peptide-22 and c(RGDfK) were picked to construct a BBB/BBTB dual-crossing, glioma-targeting liposomal drug delivery system c(RGDfK)/Pep-22-DOX-LP. In vitro cellular uptake demonstrated that the synergetic effect of c(RGDfK) and Peptide-22 could significantly increase the internalization of liposomes on U87 cells. In vivo imaging further verified that c(RGDfK)/Pep-22-LP exhibited higher brain tumor distribution than single ligand modified liposomes. The median survival time of glioma-bearing mice treated with c(RGDfK)/Pep-22-DOX-LP (39.5 days) was significantly prolonged than those treated with free doxorubicin or other controls. In conclusion, the c(RGDfK) and Peptide-22 dual-modified liposome was constructed based on the targeting ability screening of various ligands. The system could effectively overcome BBB/BBTB barriers, target to tumor cells and inhibit the growth of glioma, which proved its potential for improving the efficacy of chemotherapeutics for glioma therapy.
ACS Appl Mater Interfaces 2017 Feb 22
PMID:Peptide-22 and Cyclic RGD Functionalized Liposomes for Glioma Targeting Drug Delivery Overcoming BBB and BBTB. 2812 53

Here, a targeted delivery system was developed based on silk fibroin nanoparticles (SFNPs) for the systemic delivery of gemcitabine (Gem) to treat induced lung tumor in a mice model. For targeting the tumorigenic lung tissue, SP5-52 peptide was conjugated to Gem-loaded SFNPs. Different methods were used to characterize the structural and physicochemical properties of the SFNPs. The prepared nanoparticles (NPs) showed suitable characteristics in terms of size, zeta potential, morphology, and structural properties. Moreover, the targeted Gem-loaded SFNPs showed higher cytotoxicity, cellular uptake, and accumulation in the lung tissue in comparison to the nontargeted SFNPs and control groups. Afterward, a mice model with induced lung tumor was developed by intratracheal injection of Lewis lung carcinoma (LL/2) cells into the lungs for assessing the therapeutic efficacy of the prepared drug delivery system. The histopathological assessments and single-photon-emission computed tomography-CT radiographs showed successful lung tumor induction. Moreover, the obtained results showed higher potential of targeted Gem-loaded SFNPs in treating induced lung tumor compared with that of the control groups. Higher survival rate, less mortality, and no sign of metastasis were also observed in those animals treated with targeted NPs based on the histological and radiological analyses. This study presented an effective anticancer drug delivery system for specific targeting of induced lung tumor that could be useful in treating malignant lung cancers in future.
ACS Appl Mater Interfaces 2017 Sep 20
PMID:Targeted Delivery System Based on Gemcitabine-Loaded Silk Fibroin Nanoparticles for Lung Cancer Therapy. 2883 25