Targeted and Oxygen-Enriched Nanoplatform for Enhanced Photodynamic Therapy: In Vitro 2D Cell and 3D Spheroid Model
Chieh-Yu Chen1, Ching-Yi Chen1
1Department of Chemical Engineering, National Chung Cheng University, Chia-Yi County, 62102, Taiwan.
Abstract:
Hypoxic microenvironment and limited penetration of photosensitizers within solid tumors are two crucial factors that restrict photodynamic therapy (PDT) efficacy. Herein, a new fluorinated mixed micelle (M60@PFC-Ce6) is developed as a tumor-penetrating and oxygen-enriching nanoplatform, which consists of chlorin e6 (Ce6) and perfluorocarbons (PFCs) co-loaded into fluorinated micelles to relieve hypoxia conditions as well as folate as targeting ligand that facilitates the selective biodistribution within tumor solids. The incorporation of fluorinated copolymers into mixed micelles exhibits not only a great increase in the oxygen-loading capacity, but also improves the stability of liquid PFCs emulsion within micelles without leakage. M60@PFC-Ce6 shows excellent oxygen delivery capability, good intracellular reactive oxygen species (ROS) generation, and superior phototoxicity in vitro for both 2D monolayer of cells and 3D multicellular spheroid model. These results indicate the enriched oxygen delivery and increased cellular uptake resulting from folate-targeted ability to enhance ROS production and PDT efficacy. The penetration study of M60@PFC-Ce6 into a 3D spheroid confirms that small micellar size and folate-conjugation are beneficial for micelles to penetrate and accumulate within spheroids. Thus, a new nanoplatform with enriched oxygen-carrying amounts, better drug penetration, and stable micellar properties that relieve tumor hypoxia and improve PDT efficacy is provided.
Insights
This study introduces a novel nanoplatform (M60@PFC-Ce6) that enhances photodynamic therapy (PDT) by delivering oxygen and improving drug penetration in tumors, overcoming key limitations of current treatments.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Photodynamic therapy (PDT) efficacy is limited by tumor hypoxia and poor photosensitizer penetration.
- Developing advanced nanocarriers is crucial for overcoming these challenges in solid tumor treatment.
Purpose of the Study:
- To develop a tumor-penetrating, oxygen-enriching nanoplatform for enhanced PDT.
- To improve the delivery and efficacy of photosensitizers in solid tumors.
Main Methods:
- Fabrication of fluorinated mixed micelles (M60@PFC-Ce6) co-loading chlorin e6 (Ce6) and perfluorocarbons (PFCs).
- Incorporation of folate as a targeting ligand for selective tumor biodistribution.
- Evaluation of oxygen-loading capacity, stability, intracellular reactive oxygen species (ROS) generation, and phototoxicity in 2D and 3D cell models.
Main Results:
- The M60@PFC-Ce6 nanoplatform demonstrated enhanced oxygen delivery and improved stability.
- Folate-targeting facilitated increased cellular uptake and ROS generation, leading to superior phototoxicity.
- Penetration studies confirmed that the micellar size and folate conjugation aided accumulation within 3D spheroids.
Conclusions:
- The developed nanoplatform effectively relieves tumor hypoxia and improves PDT efficacy.
- Folate-mediated targeting and enhanced oxygen supply contribute to increased therapeutic outcomes.
- This study provides a promising strategy for overcoming PDT limitations in solid tumors.
