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An Integrated System to Remotely Trigger Intracellular Signal Transduction by Upconversion Nanoparticle-mediated Kinase Photoactivation
Published on: August 30, 2017
A multifunctional NIR responsive upconversion porphyrin nanoprobe for Fenton/FRET induced ROS amplification and
Antara Ghosh1, Archana Singh1, Subhabrata Guha2
1Department of Chemistry and Chemical Biology, Indian Institute of Technology (ISM), Dhanbad 826004, Jharkhand, India.
Abstract:
The tumor microenvironment (TME) is marked by hyperactivated signaling molecules, acidic pH, elevated GSH levels, immune evasion, and hypoxia causing therapeutic resistance. Monotherapy is restricted by various constraints in the intracellular system which calls for combinational technologies to enhance individual effects. In the present work, we have constructed a core-shell upconversion porphyrin metal organic framework (UCNP@Cu-TCPP MOF) nano drug delivery system with an in-built combinational, photodynamic (PDT) and chemodynamic therapy (CDT) under 980 nm light irradiation. A rapid microwave method was applied for synthesis of NaYF4: Yb,Er upconversion nanoparticles (UCNPs), and the shelling of porphyrin MOF was achieved through a single step in-situ method. Cu2+ is reduced to Cu+ by GSH in the TME which is reacted upon by H2O2 via Fenton reaction to produce reactive oxygen species (ROS) mainly (•OH) leading to GSH depletion and oxygen elevation in the cells. Further, NIR (near IR) light conversion through FRET mechanism between UCNP and Cu-TCPP MOF amplified the production of (1O2), confirmed with EPR and UV-visible spectroscopy. The porous structure of MOF allows ample loading of anticancer drug, Doxorubicin (∼20 %) and folic acid, facilitating targeted delivery. The pH-responsive activity of UCNP@Cu-TCPP@FA@DOX with excellent water dispersibility, stability, and biocompatibility, shows cancer cell apoptosis up to 80 %. The synthesized nano drug delivery system harnesses the photosensitizing properties of porphyrin, along with copper ions induced chemodynamic effect and targeted chemotherapy, promising a multifunctional approach towards cancer treatment.
Insights
This study developed a novel nano drug delivery system combining photodynamic and chemodynamic therapies for enhanced cancer treatment. The system effectively targets cancer cells, leading to significant apoptosis.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Materials Science
Background:
- The tumor microenvironment (TME) presents challenges like immune evasion and hypoxia, leading to therapeutic resistance.
- Monotherapy often faces intracellular limitations, necessitating combinational approaches for improved efficacy.
- Developing advanced drug delivery systems is crucial for overcoming these hurdles in cancer treatment.
Purpose of the Study:
- To construct a core-shell upconversion porphyrin metal-organic framework (UCNP@Cu-TCPP MOF) nano drug delivery system.
- To integrate photodynamic therapy (PDT) and chemodynamic therapy (CDT) for synergistic anticancer effects.
- To enhance drug delivery and therapeutic outcomes under near-infrared (NIR) light irradiation.
Main Methods:
- Synthesis of NaYF4:Yb,Er upconversion nanoparticles (UCNPs) via microwave method.
- In-situ single-step method for shelling UCNPs with porphyrin MOF (Cu-TCPP).
- Loading of Doxorubicin (DOX) and folic acid (FA) into the MOF structure for targeted delivery.
Main Results:
- The UCNP@Cu-TCPP MOF system demonstrated dual therapeutic effects: Fenton reaction-induced ROS and NIR-triggered singlet oxygen production.
- The system achieved high drug loading (∼20%) and targeted delivery facilitated by folic acid.
- The pH-responsive nano delivery system induced up to 80% cancer cell apoptosis with good biocompatibility and stability.
Conclusions:
- The developed UCNP@Cu-TCPP@FA@DOX nano system offers a multifunctional approach for cancer therapy.
- Combination of PDT, CDT, and chemotherapy shows significant potential for overcoming therapeutic resistance.
- This platform holds promise for advanced, targeted cancer treatment strategies.
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