Hybrid Liquid Crystal Nanocarriers for Enhanced Zinc Phthalocyanine-Mediated Photodynamic Therapy
Autor: | Okhil K. Nag, Jeffrey S. Erickson, Eunkeu Oh, Jawad Naciri, James B. Delehanty |
---|---|
Rok vydání: | 2018 |
Předmět: |
Indoles
medicine.medical_treatment Biomedical Engineering Pharmaceutical Science chemistry.chemical_element Bioengineering Photodynamic therapy Nanotechnology 02 engineering and technology Zinc Isoindoles 010402 general chemistry 01 natural sciences Drug Delivery Systems Liquid crystal Fluorescence Resonance Energy Transfer Organometallic Compounds medicine Humans Photosensitizer Pharmacology Zinc phthalocyanine Photosensitizing Agents Cell Membrane Organic Chemistry 021001 nanoscience & nanotechnology Liquid Crystals 0104 chemical sciences HEK293 Cells Photochemotherapy chemistry Zinc Compounds Nanoparticles Spectrophotometry Ultraviolet Nanocarriers Reactive Oxygen Species 0210 nano-technology Hydrophobic and Hydrophilic Interactions HeLa Cells Biotechnology |
Zdroj: | Bioconjugate Chemistry. 29:2701-2714 |
ISSN: | 1520-4812 1043-1802 |
Popis: | Current challenges in photodynamic therapy (PDT) include both the targeted delivery of the photosensitizer (PS) to the desired cellular location and the maintenance of PS efficacy. Zinc phthalocyanine (ZnPc), a macrocyclic porphyrin and a potent PS for PDT, undergoes photoexcitation to generate reactive singlet oxygen that kills cells efficiently, particularly when delivered to the plasma membrane. Like other commonly employed PS, ZnPc is highly hydrophobic and prone to self-aggregation in aqueous biological media. Further, it lacks innate subcellular targeting specificity. Cumulatively, these attributes pose significant challenges for delivery via traditional systemic drug delivery modalities. Here, we report the development and characterization of a liquid crystal nanoparticle (LCNP)-based formulation for the encapsulation and targeted tethering of ZnPc to the plasma membrane bilayer. ZnPc was coloaded with the organic fluorophore, perylene (PY), in the hydrophobic polymeric matrix of the LCNP core. PY facilitated the fluorescence-based tracking of the LCNP carrier while also serving as a Förster resonance energy transfer (FRET) donor to the ZnPc acceptor. This configuration availed efficient singlet oxygen generation via enhanced excitation of ZnPc from multiple surrounding PY energy donors. When excited in a FRET configuration, cuvette-based assays revealed that singlet oxygen generation from the ZnPc was ∼1.8-fold greater and kinetically 12 times faster compared to when the ZnPc was excited directly. The specific tethering of the LCNPs to the plasma membrane of HEK 293 T/17 and HeLa cells was achieved by surface functionalization of the NPs with PEGylated cholesterol. In HeLa cells, LCNPs coloaded with PY and ZnPc, when photoexcited in a FRET configuration, mediated 70% greater cell killing compared to LCNPs containing ZnPc alone (direct excitation of ZnPc). This was attributed to a significant increase of the oxidative stress in the cells during the PDT. Overall, this work details the ability of the LCNP platform to facilitate (1) the specific tethering of the PY-ZnPc FRET pair to the plasma membrane and (2) the FRET-mediated, augmented singlet oxygen generation for enhanced PDT relative to the direct excitation of ZnPc alone. |
Databáze: | OpenAIRE |
Externí odkaz: |