期刊
ACS APPLIED MATERIALS & INTERFACES
卷 11, 期 29, 页码 25730-25739出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.9b07957
关键词
tumor microenvironment; pH-sensitive; hierarchical targeting; MRI; thermo-chemotherapy; tumor theranostics
资金
- National Natural Science Foundation of China [51425303, 51603084, 51803100]
- Program for JLU Science and Technology Innovative Research Team [2017TD-06]
- Special Project from MOST of China
- Jilin University doctoral students interdisciplinary research funding project [10183201819]
Enhancement of permeability and the retention effect is one of the main pathways for the accumulation of nanomaterials in tumor sites, but poor cellular internalization and rapid clearance of nanomaterials always hamper the efficacy of imaging diagnosis and treatment. With the consideration of both high tumor accumulation and cellular internalization, positively charged nanomaterials can adhere to the tumor cell membrane by an electrostatic force, which is conducive to cellular internalization, but they are easily recognized and cleared during blood circulation. However, negatively charged nanomaterials show an enhanced stealth-like effect and possess a long blood circulation time, which is conducive to tumor accumulation. Therefore, in this work, on the basis of the shielding effect of citrate ions to positive charge and the protonation under an acidic tumor microenvironment, pH-sensitive sodium citrate-modified polyaniline nanoshuttles (NSs) with negative charge during blood circulation but positive charge in tumor sites are designed. With this hierarchical targeting strategy, the blood circulation half-life increases from 4.35 to 7.33 h, and the retention rate of NSs in tumors increases from 5.29 to 8.57% ID/g. Because the retention rate of NSs is increased, the magnetic resonance imaging resolution and signal intensity are significantly improved. A synergistic treatment of tumors is further achieved by means of photothermal therapy with laser irradiation and chemotherapy via heat-stimulated drug release.
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