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MRI-visible and pH-sensitive micelles loaded with doxorubicin for hepatoma treatment

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Abstract

Emerging pH-sensitive polymeric nanocarriers carrying therapeutic drugs are bringing about new opportunities for the effective treatment of cancer. A big challenge remains though to develop pH-sensitive polymers, which is hard to achieve via introducing only one kind of pH-sensitive chemical structure with a specific pKa. Consequently, in this study, an amphiphilic block copolymer, poly(ethylene glycol)-b-poly(β-benzyl L-aspartate) (mPEG-PBLA), was synthesized, and its PBLA block was aminolyzed by N,N-diisopropylamino ethylamine (DIP) and N,N-dibutalamino ethylamine (DBA) at different molar ratios. The copolymer mPEG-PAsp(DBA75%&DIP25%) (PPAP75%) with an appropriate pKa was screened out to form a pH-sensitive micelle, which could encapsulate a high content of the hydrophobic anticancer drug doxorubicin (DOX) and magnetic resonance imaging (MRI) contrast agent superparamagnetic iron oxide nanoparticles (SPIONs) at neutral pH, but disassemble rapidly under weak acidic conditions. The micellar nanodrug was efficiently taken up by HepG2 cells and intracellular DOX release was readily triggered inside acidic lysosomal compartments to allow migration of the free drug to the cell nucleus. In vivo fluorescence and MR bimodal imaging showed that the pegylated nanodrug with a suitable size and weak positive charge could stay longer in the blood circulation and extravasate preferentially into a tumor. The nanodrug not only exhibited high cytotoxicity in HepG2 cells but also significantly prolonged the survival time of tumor-bearing mice, thereby demonstrating the great potential of this pH-sensitive and MRI-visible micelle for the effective treatment of cancer.

Graphical abstract: MRI-visible and pH-sensitive micelles loaded with doxorubicin for hepatoma treatment

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Publication details

The article was received on 18 Nov 2018, accepted on 03 Jan 2019 and first published on 09 Jan 2019


Article type: Paper
DOI: 10.1039/C8BM01501E
Citation: Biomater. Sci., 2019, Advance Article

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    MRI-visible and pH-sensitive micelles loaded with doxorubicin for hepatoma treatment

    B. Li, M. Cai, L. Lin, W. Sun, Z. Zhou, S. Wang, Y. Wang, K. Zhu and X. Shuai, Biomater. Sci., 2019, Advance Article , DOI: 10.1039/C8BM01501E

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