Zinc Oxide Nanoparticles as Adjuvant To Facilitate Doxorubicin Intracellular Accumulation and Visualize pH-Responsive Release for Overcoming Drug Resistance

• Published in: Molecular pharmaceutics Vol. 13; no. 5; pp. 1723 - 1730
• Main Authors: Liu, Juan, Ma, Xiaowei, Jin, Shubin, Xue, Xiangdong, Zhang, Chunqiu, Wei, Tuo, Guo, Weisheng, Liang, Xing-Jie
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 02.05.2016
• Subjects: Adjuvants, Immunologic - chemistry; Adjuvants, Immunologic - pharmacology; Adjuvants, Pharmaceutic - chemistry; Adjuvants, Pharmaceutic - pharmacology; Cell Line, Tumor; Doxorubicin - chemistry; Doxorubicin - pharmacology; Drug Carriers - chemistry; Drug Delivery Systems - methods; Drug Liberation - physiology; Drug Resistance, Multiple - drug effects; Drug Resistance, Neoplasm - drug effects; Humans; Hydrogen-Ion Concentration; MCF-7 Cells; Nanomedicine - methods; Nanoparticles - chemistry; Zinc Oxide - chemistry; doxorubicin; drug resistance; drug delivery; zinc oxide nanoparticles; pH-responsive
• DOI: 10.1021/acs.molpharmaceut.6b00311
• ISSN: 1543-8384; 1543-8392

Multidrug resistance (MDR) of cancer is a challenge to effective chemotherapeutic interventions. The stimulus-responsive drug delivery system (DDS) based on nanotechnology provides a promising approach to overcome MDR. Through the development of a doxorubicin delivery system based on zinc oxide nanomaterials, we have demonstrated that MDR in breast cancer cell line can be significantly circumvented by a combination of efficient cellular uptake and a pH-triggered rapid drug release due to degradation of nanocarriers in acidic environment. Doxorubicin and zinc oxide nanoparticles, compared with free doxorubicin, effectively enhanced the intracellular drug concentration by simultaneously increasing cell uptake and decreasing cell efflux in MDR cancer cells. The acidic environment-triggered release of drug can be tracked real-time by the doxorubicin fluorescence recovery from its quenched state. Therefore, with the combination of therapeutic potential and the capacity to track release of drug in cancer cells, our system holds great potential in nanomedicine by serving dual roles of overcoming drug resistance and tracking intracellular drug release from the DDS.