Cell-penetrating peptide conjugates to enhance the antitumor effect of paclitaxel on drug-resistant lung cancer

To conquer the drug resistance of tumors and the poor solubility of paclitaxel (PTX), two PTX-cell-penetrating peptide conjugates (PTX-CPPs), PTX-TAT and PTX-LMWP, were synthesized and evaluated for the first time. Compared with free PTX, PTX-CPPs displayed significantly enhanced cellular uptake, el...

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Bibliographic Details
Published in:Drug delivery 2017-11, Vol.24 (1), p.752-764
Main Authors: Duan, Ziqing, Chen, Cuitian, Qin, Jing, Liu, Qi, Wang, Qi, Xu, Xinchun, Wang, Jianxin
Format: Article
Language:English
Subjects:
A549 Cells
Animals
Antineoplastic Agents, Phytogenic
Apoptosis
cell-penetrating peptide
Cell-Penetrating Peptides
conjugate
Drug resistance
Drug Resistance, Neoplasm
drug-resistant lung cancer
Humans
low molecular weight protamine
Lung cancer
Lung Neoplasms
Mice
Paclitaxel
Peptides
TAT
Tumors
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Summary:To conquer the drug resistance of tumors and the poor solubility of paclitaxel (PTX), two PTX-cell-penetrating peptide conjugates (PTX-CPPs), PTX-TAT and PTX-LMWP, were synthesized and evaluated for the first time. Compared with free PTX, PTX-CPPs displayed significantly enhanced cellular uptake, elevated cell toxicity, increased cell apoptosis, and decreased mitochondrial membrane potential (Δψm) in both A549 and A549T cells. PTX-LMWP exhibited a stronger inhibitory effect than PTX-TAT in A549T cells. Analysis of cell-cycle distribution showed that PTX-LMWP influenced mitosis in drug-resistant A549T tumor cells via a different mechanism than PTX. PTX-CPPs were more efficient in inhibiting tumor growth in tumor-bearing mice than free PTX, which suggested their better in vivo antitumor efficacy. Hence, this study demonstrates that PTX-CPPs, particularly PTX-LMWP, have outstanding potential for inhibiting the growth of tumors and are a promising approach for treating lung cancer, especially drug-resistant lung cancer.
ISSN:1071-7544
1521-0464
DOI:10.1080/10717544.2017.1321060