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Published on: May 22, 2020
Self-Assembly Nanoparticles for Overcoming Multidrug Resistance and Imaging-Guided Chemo-Photothermal Synergistic
Haiyan Gao1,2, Yan Bai1,2, Lijuan Chen1,2
1Henan Provincial People's Hospital & Zhengzhou University People's Hospital, Zhengzhou 450003, People's Republic of China.
Background And Purpose:
The development of multiple drug resistance (MDR) to chemotherapy and single modal therapy remains unsatisfied for the eradication of tumor, which are major obstacles in cancer therapy. This novel system with excellent characteristics for inhibition of P-glycoprotein (P-gp), and for near-infrared fluorescence (NIRF) imaging-guided chemo-photothermal therapy (PTT), has been identified as a promising way to MDR and achieve synergistic cancer therapy.
Methods:
In this study, we successfully synthesized a multifunctional theranostic system, which was developed through FDA-approved self-assembling drugs, which contain anticancer drug doxorubicin (Dox), imaging and high photothermal conversion drug indocyanine green (ICG) and P-gp regulator TPGS (the system named T/Dox-ICG). We studied the characterization of T/Dox-ICG NPs, including the TEM, SEM, DLS, UV-vis-NIR, zeta potential, CLSM, in vitro FL imaging, in vitro photothermal effect, in vitro Dox and ICG release. We used CLSM to verify the location of intracellular distribution of Dox in SCG 7901/VCR cells, Western blot was performed to demonstrate the TPGS-mediated inhibition of P-gp. And, the cytotoxicity of materials against SCG 7901/VCR cells was studied by the MTT assay.
Results:
The TEM showed the T/Dox-ICG NPs had good monodispersity with diameters of 19.03 nm, Dox and ICG could be released constantly from T/Dox-ICG NPs in vitro. In vitro cell experiments demonstrated higher Dox accumulation and retention in the nucleus. Western blot showed TPGS could obviously inhibit the expression of P-gp. In vitro cytotoxicity assay showed more significant cytotoxicity on MDR cells (SCG 7901/VCR) with only 8.75% of cells surviving.
Conclusion:
MDR cancer therapy indicates that it may be important to develop a safer system that can simultaneously inhibit the drug transporters and monitor the delivery of chemotherapeutic agents, and combination therapy have raised widespread concern on tumor treatment.
Insights
This study presents a novel theranostic system for treating multidrug-resistant (MDR) cancers. The system combines chemotherapy, photothermal therapy, and P-glycoprotein inhibition for enhanced tumor eradication.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Multidrug resistance (MDR) to chemotherapy is a significant challenge in cancer treatment.
- Existing therapies often fail to eradicate tumors due to resistance mechanisms like P-glycoprotein (P-gp) expression.
Purpose of the Study:
- To develop a multifunctional theranostic system for overcoming MDR in cancer.
- To combine chemotherapy, photothermal therapy, and P-gp inhibition for synergistic anti-cancer effects.
Main Methods:
- Synthesis of a self-assembling nanoparticle system (T/Dox-ICG) containing doxorubicin (Dox), indocyanine green (ICG), and TPGS.
- Characterization of nanoparticles using TEM, SEM, DLS, and UV-vis-NIR spectroscopy.
- In vitro evaluation of drug release, cellular uptake, P-gp inhibition via Western blot, and cytotoxicity assays.
Main Results:
- T/Dox-ICG nanoparticles exhibited good monodispersity (19.03 nm) and sustained release of Dox and ICG.
- TPGS effectively inhibited P-gp expression in MDR cancer cells.
- Significant cytotoxicity was observed in MDR cells, with only 8.75% cell survival.
Conclusions:
- The developed theranostic system shows promise for treating MDR cancers.
- Simultaneous inhibition of drug transporters and monitoring of drug delivery are crucial for effective MDR cancer therapy.
