title: Surface protonation/deprotonation controlled instant affinity switch of nano drug vehicle (NDV) for pH triggered tumor cell targeting.
abstract: 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.
authors.affiliation: Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China.
authors.forename: Guanglong
authors.initials: G
authors.lastname: Ma
authors.affiliation: Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China.
authors.forename: Zhefan
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China.
authors.forename: Longgang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Chemical Engineering and Department of Bioengineering, University of Missouri, Columbia, MO, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Bernards
authors.affiliation: Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China; Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Biomedical Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210046, China. Electronic address: schen@zju.edu.cn.
authors.forename: Shengfu
authors.initials: S
authors.lastname: Chen
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D011522:Protons; D013499:Surface Properties; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D053769:Nanocapsules; D011522:Protons; D004317:Doxorubicin
keywords: Affinity switch; Nano drug vehicle; Surface protonation; Tumor cell targeting; pH sensitive