期刊
CHEMISTRY-A EUROPEAN JOURNAL
卷 27, 期 59, 页码 14610-14618出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.202101842
关键词
camptothecin; combination therapy; doxorubicin; mesoporous silica nanoparticles; photodynamic therapy; phthalocyanine
资金
- Generalitat de Catalunya for the Consolidated Research Group Grant [2017 SGR 01559]
- MINECO [RTI2018-094734-B-C22, CTQ2017-85393-P, PID2020-116490GB-I00]
- ERA-NET/European Commission/MINECO [EuroNanoMed2017-191 / PCIN-2017-042]
- Severo Ochoa Programme for Centres of Excellence in RD (MINECO) [SEV2016-0686]
- IQS
The pH-responsive drug delivery system based on mesoporous silica nanoparticles has been developed for delivery of three anticancer drugs with different modes of action. The system combines synergistic chemotherapy and photodynamic therapy, allowing for selective release of drugs in the acidic environment of tumor cells. In vitro studies have shown endocytosis of the system into HeLa and HepG2 cells, with subsequent release of drugs.
A pH-responsive drug delivery system (DDS) based on mesoporous silica nanoparticles (MSNs) has been prepared for the delivery of three anticancer drugs with different modes of action. The novelty of this system is its ability to combine synergistic chemotherapy and photodynamic therapy. A photoactive conjugate of a phthalocyanine (Pc) and a topoisomerase I inhibitor (topo-I), namely camptothecin (CPT), linked by a poly(ethylene glycol) (PEG) chain has been synthesized and then loaded into the mesopores of MSNs. Doxorubicin (DOX), which is a topoisomerase II inhibitor (topo-II), has also been covalently anchored to the outer surface of the MSNs through a dihydrazide PEG linker. In the acidic environment of tumor cells, selective release of the three drugs takes place. In vitro studies have demonstrated the endocytosis of the system into HeLa and HepG2 cells, and the subsequent release of the three drugs into the cytoplasm and nucleus. Furthermore, the cytotoxic effect of DOX, CPT and Pc has been assessed in vitro before and upon light irradiation.
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