Co-Delivery of Cisplatin Prodrug and Chlorin e6 by Mesoporous Silica Nanoparticles for Chemo-Photodynamic Combination Therapy to Combat Drug Resistance
- 17 May 2016
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Applied Materials & Interfaces
- Vol. 8 (21), 13332-13340
- https://doi.org/10.1021/acsami.6b03881
Abstract
Combination therapy shows great promise in circumventing cisplatin resistance. We report herein the development of a novel nanoscale drug delivery system (nDDS) based nanotherapeutic that combines chemotherapy and photodynamic therapy (PDT) into one single platform to achieve synergistic anticancer capacity to conquer cisplatin resistance. Mesoporous silica nanoparticle (MSNs) was used as the drug delivery vector to conjugate cisplatin prodrug and to load photosensitizer chlorin e6 (Ce6) to afford the dual drug loaded delivery system MSNs/Ce6/Pt. The hybrid nanoparticles have an average diameter of about 100 nm and slightly positive surface charge of about 18.2 mV. The MSNs/Ce6/Pt nanoparticles can be efficiently internalized by cells through endocytosis, thereby achieving much higher cellular Pt uptake than cisplatin in cisplatin-resistant A549R lung cancer cells. After 660 nm light irradiation (10 mW/cm2), the cellular reactive oxygen species (ROS) level in MSNs/Ce6/Pt treated cells was elevated dramatically. As a result of these properties, MSNs/Ce6/Pt exhibited very potent anticancer activity against A549R cells, giving a half-maximal inhibitory concentration (IC50) value for the combination therapy of 0.53 μM, much lower than that of cisplatin (25.1 μM). This study suggests the great potential of nDDS-based nanotherapeutic for combined chemo-photodynamic therapy to circumvent cisplatin resistance.Keywords
Funding Information
- Ministry of Education of the People's Republic of China (IRT1298)
- Ministry of Science and Technology of the People's Republic of China (2014CB845604, 2015CB856301)
- National Natural Science Foundation of China (21201183, 21231007, 21572282)
- Guangdong Provincial Department of Science and Technology
- the Fundamental Research Funds for the Central Universities
- Guangdong Provincial Department of Human Resources and Social Security
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