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Phenylboronic Acid-Functionalized Polyamidoamine-Mediated Bcl-2 siRNA Delivery for Inhibiting the Cell Proliferation

Di Wu, Jiebing Yang, Zhen Xing, Haobo Han, Tingting Wang, Aijun Zhang, Yan Yang, Quanshun Li

Colloids Surf B Biointerfaces. 2016 Oct 1;146:318-25.

PMID: 27371891

Abstract:

In this study, the conjugation of phenylboronic acid (PBA) to amine-terminated polyamidoamine (PAMAM) was successfully conducted to prepare a tumor-targeted gene carrier PBA-functionalized PAMAM (PPP) for Bcl-2 siRNA delivery, using a heterobifunctional crosslinker NHS-PEG5k-Mal. The carrier possessed favorable capacity for siRNA condensation and could protect siRNA from the degradation against RNase and serum. The introduction of PBA could facilitate the cellular uptake and further transfection of Bcl-2 siRNA demonstrated by confocal laser scanning microscopy and flow cytometry. Meanwhile, PPP-mediated transfection of Bcl-2 siRNA could significantly inhibit the expression of Bcl-2 gene at both mRNA and protein levels. Furthermore, owing to the knock-down of Bcl-2, PPP/siRNA could significantly inhibit the cell proliferation by inducing the cell apoptosis, and also enhance the antitumor efficiency of doxorubicin by suppressing the resistance of tumor cells to chemotherapeutics. In conclusion, the PPP-mediated Bcl-2 siRNA delivery could potentially be an effective platform for solving the drug resistance and further achieving the combined chemotherapy and gene therapy in tumor treatment.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP870779014 2-(4′-Fluorobenzyloxy)phenylboronic acid 2-(4′-Fluorobenzyloxy)phenylboronic acid 870779-01-4 Price
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