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Updated: Mar 13, 2026
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Pluronic-attached polyamidoamine dendrimer conjugates overcome drug resistance in breast cancer
Meng Wang1, Ying Li1, Mingyi HuangFu1
1Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
Aim:
To design pluronic F68 (PF68)-conjugated polyamidoamine (PAMAM) dendrimer conjugates for doxorubicin (DOX) delivery for overcoming multidrug resistance, and clarify the reversal mechanism.
Materials & Methods:
A series of PAMAM-PF68 conjugates were designed. The antitumor activity of the DOX-loaded conjugates was evaluated against MCF-7/ADR cells, tumor spheroids and tumors. Several bioinformatics were detected to characterize the reversal mechanism.
Results:
Increased antitumor activity of the DOX-loaded conjugates was achieved in vitro and in vivo. The complexes induced more DOX accumulation via caveolae-mediated endocytosis. After escaping from the endosome/lysosome, the nuclear trafficking of DOX was achieved. Apoptosis was significantly increased by regulating mitochondrial function and gene expression.
Conclusion:
With optimized PF68 modification, PAMAM-PF68 conjugates can significantly overcome multidrug resistance in vitro and in vivo.
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