Significant increase in the water dispersibility of zinc phthalocyanine nanowires and applications in cancer phototherapy

Abstract

The phototherapy is one of the widely accepted noninvasive clinical methodologies to eradicate cancer cells owing to its minimal side effects and high selectivity to the light of specific wavelength. As represented by photodynamic (PD) and photothermal (PT) therapy, the phototherapy requires light and photosensitizer to generate reactive oxygen species and heat, respectively. Zinc phthalocyanine (ZnPc) is one of the promising photosensitizers as it has a strong absorption cross-section in the spectral range of 650-900 nm that guarantees maximum tissue penetration. One critical issue in using Pc molecule, including ZnPc as a biocompatible sensitizer is the poor water solubility. To increase water solubility, various chemical modifications inducing hydrophilicity have been widely attempted to introduce various functional groups in the ZnPc backbone. We report that ZnPc nanowires (NWs) directly grown from ZnPc powder by vaporization-condensation-recrystallization process show surprisingly increased water dispersibility without any functionalization. The ZnPc NW solution exhibits highly efficient dual PD and PT effects upon the irradiation of near infrared (808 nm) laser. The dual phototherapeutic effect of ZnPc NW is proven to enhance cytotoxic efficiency according to both in vitro and in vivo experimental results. NPG Asia Materials (2012) 4, e12; doi:10.1038/am.2012.22; published online 13 April 2012Keywords: nanowire; photosensitizer; phototherapy; Zinc phthalocyanine INTRODUCTION Phototherapy, represented by photodynamic therapy (PDT) and photothermal therapy (PTT), is an advanced modality for the treatment of malignant tumors as it is widely used for clinical cancer treatments. PDT selectively destroys neoplastic lesions using cytotoxic reactive oxygen species (ROS) generated by light activation of the photosensitizer. 1,2 One of the crucial factors determining the PDT efficacy is the photochemical and photophysical properties of the photosensitizer. 3,4 Currently, four main classes of photosensitizer, such as porphyrin derivatives, chlorins, porphycenes, and phthalocyanines (Pcs), have been approved by the U.S. Food and Drug Administration (FDA) for clinical applications against cancer. 5,6 Among these, metallo-phthalocyanine has attracted considerable interest, having a photodynamic (PD) property that can be readily tuned by the type of central metal ion and the functional groups introduced as a Pc ring substituent. Zinc phthalocyanine (ZnPc) is known to exhibit a high PD effect as it possesses a diamagnetic Zn(II) central metal ion whose d shell is fully occupied, by which the yield of triplet excited state with long lifetime essential for the generation of ROS becomes high. 7 Moreover, ZnPc has

Solvent impact on the planarity and aromaticity of free and monohydrated zinc phthalocyanine: a theoretical study

“…In this case, the desired solubility could be achieved by introducing several polar groups (for example, carboxylic or sulfonic) to the external benzene rings [18]. The other way of increased water dispersibility, with solubility increased from 16 to 120 mg/l, was recently reported as a result of ZnPc nanowire formation, directly grown from powdered ZnPc [17]. On the other hand, a basic (unsubstituted) ZnPc molecule could be selected as a good computational model, mimicking a less or more distorted structure of its more complex derivatives [18].…”

“…1a) is interesting primary due to the fact that Zn(II) ion with d 10 configuration does not contribute directly to the electronic spectra of phthalocyanine, dominated by transitions within their π-electronic system, formed by several conjugated C=N and C=C double bonds. Thus, reliable prediction of ZnPc molecular and electronic structure as well as spectroscopic properties could help in designing novel PDT agents [17], including their water-soluble derivatives, and understanding their action, based on photochemical reactions and electronic transitions between the ground and excited states.…”

“…In the case of insoluble compounds, special ways of delivery within patient body are required. However, unsubstituted metallophthalocyanines, including ZnPc, are practically not soluble in water [17]. In this case, the desired solubility could be achieved by introducing several polar groups (for example, carboxylic or sulfonic) to the external benzene rings [18].…”

Tuning drug release in polyester thin films: terminal end-groups determine specific rates of additive-free controlled drug release

“…29 Pulses of light create more carboxylic acid end-groups and would allow a gradual increase in drug delivery as needed. Similar formation of acidic end-groups can be envisioned by other 'SMART' triggered events (for example, ultrasound, electrical signal, light, temperature 30 ) for switchable hydrophobic/hydrophilic surfaces. 31 This would allow modulation of drug release, and after the drug reservoir is exhausted, subsequent triggers would allow the forced erosion of medical implants, resulting in faster clearance.…”

Nanomaterials for Photo-Based Diagnostic and Therapeutic Applications

“…Among the different photosensitizers in use today, metallo-phthalocyanine has attracted substantial interest due to their photodynamic (PD) properties that can be easily tuned by the type of metal ion involved. For example, zinc-phthalocyanine nanowires synthesized by Moon et al 71 showed excellent photosensitizing capabilities as well as highly efficient dual PD and photothermal (PT) effects upon irradiation of NIR laser. Studies performed by Jeong et al 70 also demonstrated the use of photosensitizer-conjugated human serum albumin NPs as impressive photodynamic drug delivery candidates with good biocompatibility and tumor-targeting abilities.…”