Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 13, Issue 27, Pages 31440-31451Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c06440
Keywords
metal-organic nanomaterials; Mn(III) ions; drug delivery; photodynamic therapy; chemotherapy
Funding
- Natural Science Foundation of Shanghai [18ZR1401700]
- National Natural Science Foundation of China [51972056, 51773036, 52002061]
- Shanghai Shuguang Program [18SG29]
- Program of Shanghai Academic/Technology Research Leader [20XD1420200]
- Major Science and Technology Innovation Project of Shandong Province [2019JZZY011108]
- Innovation Program of the Shanghai Municipal Education Commission [2017-01-07-00-03-E00055]
- China the Postdocoral Science Foundation [2020M670945]
- DHU Distinguished Young Professor Program
- Fundamental Research Funds for the Central Universities
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This study developed a GSH-sensitive NDDS with high biosafety, cancer specificity, and multifunctionality for effective synergistic treatment. By loading doxorubicin in DOX@MnCPs/PEG, the NDDS showed efficient tumor homing and significant suppression of tumor growth in vivo through synergistic photodynamic-chemo therapy.
Activatable nanoscale drug delivery systems (NDDSs) are promising in maximizing cancer specificity and anticancer efficacy, and a multifunctional metal-organic nanomaterial is one of the new star NDDSs which requires further exploration. Herein, a novel DOX@MnCPs/PEG NDDSs were constructed by first synthesizing Mn3+-sealed coordination particles (MnCPs), modified with a targeted PEGylated polymer, and then loading anticancer drug doxorubicin (DOX). MnCPs were prepared from the assembly of Mn3+ ions and hematoporphyrin monomethyl ether (HMME) molecules. Furthermore, MnCPs had an average size of similar to 100 nm and a large surface area (similar to 52.6 m(2) g(-1)) and porosity (similar to 3.6 nm). After the loading of DOX, DOX@MnCPs/PEG exhibited a high DOX-loading efficacy of 27.2%, and they reacted with glutathione (GSH) to confer structural collapse, leading to the production of Mn2+ ions for enhanced magnetic resonance imaging (MRI), free HMME for augmented photodynamic effect, and free DOX for chemotherapy. As a consequence, these DOX@MnCPs/PEG NDDSs after intravenous injection showed efficient tumor homing and then exerted an obvious suppression for tumor growth rate by synergistic photodynamic-chemo therapy in vivo. Importantly, most of the DOX@MnCPs/PEG NDDSs could be gradually cleared through the renal pathway, and the remaining part could slowly be metabolized via the feces, enabling high biosafety. Therefore, this work provides a type of GSH-sensitive NDDS with biosafety, caner specificity, and multifunctionality for high synergistic treatment efficacy.
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