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Updated: Apr 14, 2026
Photodynamic Therapy with Blended Conducting Polymer/Fullerene Nanoparticle Photosensitizers
Published on: October 28, 2015
Dendritic nanoconjugates of photosensitizer for targeted photodynamic therapy
Ahu Yuan1, Bing Yang2, Jinhui Wu3
1Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China.
Abstract:
Application of photodynamic therapy for treating cancers has been restrained by suboptimal delivery of photosensitizers to cancer cells. Nanoparticle (NP)-based delivery has become an important strategy to improve tumor delivery of photosensitizers; however, the success is still limited. One problem for many NPs is poor penetration into tumors, and thus the photokilling is not complete. We aimed to use chemical conjugation method to engineer small NPs for superior cancer cell uptake and tumor penetration. Thus, Chlorin e6 (Ce6) was covalently conjugated to PAMAM dendrimer (generation 7.0) that was also modified by tumor-targeting RGD peptide. With multiple Ce6 molecules in a single nanoconjugate molecule, the resultant targeted nanoconjugates showed uniform and monodispersed size distribution with a diameter of 28 nm. The singlet oxygen generation efficiency and fluorescence intensity of the nanoconjugates in aqueous media were significantly higher than free Ce6. Targeted nanoconjugates demonstrated approximately 16-fold enhancement in receptor-specific cellular delivery of Ce6 into integrin-expressing A375 cells compared to free Ce6 and thus were able to cause massive cell killing at low nanomolar concentrations under photo-irradiation. In contrast, they did not cause significant toxicity up to 2 μM in dark. Due to their small size, the targeted nanoconjugates could penetrate deeply into tumor spheroids and produced strong photo-toxicity in this 3-D tumor model. As a result of their great cellular delivery, small size, and lack of dark cytotoxicity, the nanoconjugates may provide an effective tool for targeted photodynamic therapy of solid tumors.
Insights
Engineered small nanoparticles improve photodynamic therapy by enhancing photosensitizer delivery and tumor penetration. This targeted approach offers effective cancer cell killing with minimal dark toxicity, advancing solid tumor treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Photodynamic therapy (PDT) efficacy is limited by poor photosensitizer delivery to cancer cells.
- Nanoparticle (NP)-based delivery strategies show promise but face challenges with tumor penetration.
- Incomplete tumor photokilling results from inadequate NP penetration.
Purpose of the Study:
- To engineer small nanoparticles for enhanced cancer cell uptake and tumor penetration using chemical conjugation.
- To improve the delivery and efficacy of photosensitizers in photodynamic therapy.
- To develop a targeted nanoconjugate for effective solid tumor treatment.
Main Methods:
- Covalent conjugation of Chlorin e6 (Ce6) photosensitizer to RGD peptide-modified PAMAM dendrimer (generation 7.0).
- Characterization of nanoconjugate size, singlet oxygen generation, and fluorescence.
- In vitro evaluation of cellular delivery, phototoxicity, and dark toxicity in A375 cells and 3-D tumor spheroids.
Main Results:
- Developed uniform, monodispersed 28 nm targeted nanoconjugates with enhanced singlet oxygen generation and fluorescence.
- Achieved a 16-fold increase in receptor-specific cellular delivery of Ce6 into A375 cells compared to free Ce6.
- Demonstrated deep tumor spheroid penetration and significant phototoxicity at low nanomolar concentrations with no dark toxicity.
Conclusions:
- Small, targeted nanoconjugates offer superior cellular delivery and tumor penetration for photodynamic therapy.
- The developed nanoconjugates show high efficacy in killing cancer cells with minimal toxicity.
- These nanoconjugates represent a promising tool for targeted photodynamic therapy of solid tumors.
