Dataset Information

Enhancement of Antitumor Efficacy of Paclitaxel-Loaded PEGylated Liposomes by N,N-Dimethyl Tertiary Amino Moiety in Pancreatic Cancer.

ABSTRACT: Introduction:Pancreatic cancer, or pancreatic duct adenocarcinoma (PDAC), remains one of the most lethal cancers and features insidious onset, highly aggressive behavior and early distant metastasis. The dense fibrotic stroma surrounding tumor cells is thought to be a shield to resist the permeation of chemotherapy drugs in the treatment of PDAC. Thus, we synthesized a pancreas-targeting paclitaxel-loaded PEGylated liposome and investigated its antitumor efficacy in the patient-derived orthotopic xenograft (PDOX) nude mouse models of PDAC. Methods:The PTX-loaded PEGylated liposomes were prepared by film dispersion-ultrasonic method and modified by an N,N-dimethyl tertiary amino residue. Morphology characteristics of the PTX-loaded liposomes were observed by transmission electron microscope (TEM). The PDOX models of PDAC were established by orthotopic implantation and imaged by a micro positron emission tomography/computed tomography (PET/CT) imaging system. The in vivo distribution and antitumor study were then carried out to observe the pancreas-targeting accumulation and the antitumor efficacy of the proposed PTX liposomes. Results:PTX loaded well into both modified (PTX-Lip2N) and unmodified (PTX-Lip) PEGylated liposomes with spherical shapes and suitable parameters for the endocytosis process. The PDOX nude mouse models were successfully created in which high 18F-FDG intaking regions were observed by micro-PET/CT. In addition to higher cellular uptakes of PTX-Lip2N by the BxPC-3 cells, the proposed nanoparticle had a notable penetrating ability towards PDAC tumor tissues, and consequently, the antitumor ability of PTX-Lip2N was significantly superior to the unmodified PTX-Lip in vivo PDOX models and even more effective than nab-PTX in restraining tumor growth. Conclusion:The modified pancreas-targeting PTX-loaded PEGylated liposomes provide a promising platform for the treatment of pancreatic cancer.

SUBMITTER: Chen Y

PROVIDER: S-EPMC7398872 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Enhancement of Antitumor Efficacy of Paclitaxel-Loaded PEGylated Liposomes by N,N-Dimethyl Tertiary Amino Moiety in Pancreatic Cancer.

Chen Yang Y Wang Li L Luo Shi S Hu Jun J Huang Xing X Li Pei-Wen PW Zhang Yi Y Wu Chao C Tian Bo-Le BL

Drug design, development and therapy 20200723

<h4>Introduction</h4>Pancreatic cancer, or pancreatic duct adenocarcinoma (PDAC), remains one of the most lethal cancers and features insidious onset, highly aggressive behavior and early distant metastasis. The dense fibrotic stroma surrounding tumor cells is thought to be a shield to resist the permeation of chemotherapy drugs in the treatment of PDAC. Thus, we synthesized a pancreas-targeting paclitaxel-loaded PEGylated liposome and investigated its antitumor efficacy in the patient-derived o ...[more]

PMID: 32801636

Similar Datasets

Project description:In the present study, we prepared a novel delivery system of iRGD (CRGDK/RGPD/EC)-modified sterically stabilized liposomes (SSLs) containing conjugated linoleic acid-paclitaxel (CLA-PTX). The anti-tumor effect of iRGD-SSL-CLA-PTX was investigated on B16-F10 melanoma in vitro and in vivo. The in vitro targeting effect of iRGD-modified SSLs was investigated in a real-time confocal microscopic analysis experiment. An endocytosis-inhibition assay was used to evaluate the endocytosis pathways of the iRGD-modified SSLs. In addition, the in vitro cellular uptake and in vitro cytotoxicity of iRGD-SSL-CLA-PTX were evaluated in B16-F10 melanoma cells. In vivo biodistribution and in vivo antitumor effects of iRGD-SSL-CLA-PTX were investigated in B16-F10 tumor-bearing mice. The induction of apoptosis by iRGD-SSL-CLA-PTX was evaluated in tumor-tissue sections. Real-time confocal microscopic analysis results indicated that the iRGD-modified SSLs internalized into B16-F10 cells faster than SSLs. The identified endocytosis pathway of iRGD-modified SSLs indicated that energy- and lipid raft-mediated endocytosis played a key role in the liposomes' cellular uptake. The results of the cellular uptake experiment indicated that the increased cellular uptake of CLA-PTX in the iRGD-SSL-CLA-PTX-treated group was 1.9-, 2.4-, or 2.1-fold compared with that in the CLA-PTX group after a 2-, 4-, or 6-hour incubation, respectively. In the biodistribution test, the CLA-PTX level in tumor tissues from iRGD-SSL-CLA-PTX-treated mice at 1 hour (1.84±0.17 ?g/g) and 4 hours (1.17±0.28 ?g/g) was 2.3- and 2.0-fold higher than that of CLA-PTX solution at 1 hour (0.79±0.06 ?g/g) and 4 hours (0.58±0.04 ?g/g). The value of the area under the curve for the first 24 hours in the tumors of iRGD-SSL-CLA-PTX-treated mice was significantly higher than that in the SSL-CLA-PTX and CLA-PTX solution-treated groups (P<0.01). The in vivo antitumor results indicated that iRGD-SSL-CLA-PTX significantly inhibited the growth of B16-F10 tumors compared with the SSL-CLA-PTX or CLA-PTX solution-treatment groups (P<0.01). The results of tumor-cell apoptosis showed that tumors from the iRGD-SSL-CLA-PTX-treated group exhibited more advanced cell apoptosis compared with the control, CLA-PTX solution-, and SSL-CLA-PTX-treated groups. In conclusion, the antitumor effect of iRGD-SSL-CLA-PTX was confirmed on B16-F10 melanoma in vitro and in vivo.

Dataset Information

Enhancement of Antitumor Efficacy of Paclitaxel-Loaded PEGylated Liposomes by N,N-Dimethyl Tertiary Amino Moiety in Pancreatic Cancer.

Publications

Enhancement of Antitumor Efficacy of Paclitaxel-Loaded PEGylated Liposomes by N,N-Dimethyl Tertiary Amino Moiety in Pancreatic Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets