TY - JOUR
T1 - Nanoparticles for Triple Drug Release for Combined Chemo- and Photodynamic Therapy
AU - Martínez-Edo, Gabriel
AU - Xue, Evelyn Y.
AU - Ha, Summer Y.Y.
AU - Pontón, Iris
AU - González-Delgado, José Antonio
AU - Borrós, Salvador
AU - Torres, Tomás
AU - Ng, Dennis K.P.
AU - Sánchez-García, David
N1 - Funding Information:
A fellowship by the IQS (G.M.E.) is gratefully acknowledged. We would like to thank Generalitat de Catalunya for the Consolidated Research Group Grant 2017 SGR 01559 to GEMAT. Financial support from MINECO (RTI2018‐094734‐B‐C22, CTQ2017‐85393‐P and PID2020‐116490GB‐I00) and ERA‐NET/European Commission/MINECO (EuroNanoMed2017‐191 / PCIN‐2017‐042) is acknowledged. IMDEA Nanociencia acknowledges support from the “Severo Ochoa” Programme for Centres of Excellence in R&D (MINECO, Grant SEV2016‐0686). The authors thank Dra. Cristina Fornaguera for her assistance in confocal microscopy.
Funding Information:
A fellowship by the IQS (G.M.E.) is gratefully acknowledged. We would like to thank Generalitat de Catalunya for the Consolidated Research Group Grant 2017 SGR 01559 to GEMAT. Financial support from MINECO (RTI2018-094734-B-C22, CTQ2017-85393-P and PID2020-116490GB-I00) and ERA-NET/European Commission/MINECO (EuroNanoMed2017-191 / PCIN-2017-042) is acknowledged. IMDEA Nanociencia acknowledges support from the ?Severo Ochoa? Programme for Centres of Excellence in R&D (MINECO, Grant SEV2016-0686). The authors thank Dra. Cristina Fornaguera for her assistance in confocal microscopy.
Publisher Copyright:
© 2021 Wiley-VCH GmbH
PY - 2021/10/21
Y1 - 2021/10/21
N2 - 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.
AB - 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.
KW - camptothecin
KW - combination therapy
KW - doxorubicin
KW - mesoporous silica nanoparticles
KW - photodynamic therapy
KW - phthalocyanine
UR - http://www.scopus.com/inward/record.url?scp=85116016433&partnerID=8YFLogxK
U2 - 10.1002/chem.202101842
DO - 10.1002/chem.202101842
M3 - Article
C2 - 34460988
AN - SCOPUS:85116016433
SN - 0947-6539
VL - 27
SP - 14610
EP - 14618
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 59
ER -