期刊
BIOMATERIALS
卷 62, 期 -, 页码 116-127出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.05.020
关键词
Surface protonation; Affinity switch; Nano drug vehicle; pH sensitive; Tumor cell targeting
资金
- National Nature Science Foundation of China [21174127, 21474085, 31350110223]
- Ph.D. Programs Foundation of Ministry of Education of China [20110101110034]
- Zhejiang Provincial Natural Science Foundation of China [LZ13E030001]
- Department Education of Zhejiang Province [Z200804487]
To realize a fast and selective capture of nano drug vehicles (NDVs) by malignant tumors, an instant affinity switchable NDV based on pH-sensitive surface protonation was prepared. This NDV is prepared from a zwitterionic polymer system with an ultra resistant poly(carboxybetaine) (pCB) shell and sulfo groups near a hydrophobic doxorubicin (DOX) loaded core. The results show that this new NDV system had an instant and sensitive affinity switch from strong resistance in physiological pH to a high affinity to tumor cell membranes in the slightly acidic extracellular pH of malignant tumors depending on if the net charge of the NDV is reversed or not. The pH of this affinity switch can be controlled by the amount of the strong acidic sulfo groups that act as the zeta potential adjustor of the NDV near the inner hydrophobic core. As a result, this CB-based NDV was captured by solid tumor tissue efficiently and thus inhibited tumor growth much more effectively than the PEGylated NDV system, while eliminating unwanted side effects in other healthy tissues. This indicates that the affinity switch caused by protein-like surface protonation of the NDV is much more efficient than the traditional charge switchable NDV approaches. (c) 2015 Elsevier Ltd. All rights reserved.
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