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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| http://dx.doi.org/10.2217/nnm-2016-0252 | DOI Listing |
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