There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Gold nanoparticles (AuNPs) have been extensively studied within biomedicine due to their biocompatibility and low toxicity. In particular, AuNPs have been widely used to deliver photosensitiser agents for photodynamic therapy (PDT) of cancer. Here we review the state-of-the-art for the functionalisation of the gold nanoparticle surface with both photosensitisers and targeting ligands for the active targeting of cancer cell surface receptors. From the initial use of the AuNPs as a simple carrier of the photosensitiser for PDT, the field has significantly advanced to include: the use of PEGylated modification to provide aqueous compatibility and stealth properties for in vivo use; gold metal-surface enhanced singlet oxygen generation; functionalisation of the AuNP surface with biological ligands to specifically target over-expressed receptors on the surface of cancer cells and; the creation of nanorods and nanostars to enable combined PDT and photothermal therapies. These versatile AuNPs have significantly enhanced the efficacy of traditional photosensitisers for both in vitro and in vivo cancer therapy. From this review it is apparent that AuNPs have an important future in the treatment of cancer.

Photosensitiser-gold nanoparticle conjugates for photodynamic therapy of cancer

Photodynamic therapy (PDT) is a minimally invasive technique which has proven to be successful in the treatment of several types of tumors. This relatively simple method exploits three inseparable elements: phototoxic compound (photosensitizer [PS]), light source, and oxygen. Upon irradiation by light with specified wavelength, PS generates reactive oxygen species, which starts the cascade of reactions leading to cell death. The positive therapeutic outcome of PDT may be limited due to several aspects, including low water solubility of PSs, hampering their effective administration and blood circulation, as well as low tumor specificity, inefficient cellular uptake and activation energies requiring prolonged illumination times. One of the promising approaches to overcome these obstacles involves the use of carrier systems modulating pharmacokinetics and pharmacodynamics of the PSs. In the present review, we summarized current in vitro and in vivo studies regarding the use of nanoparticles as potential delivery devices for PSs to enhance their cellular uptake and cytotoxic properties, and thus-the therapeutic outcome of PDT. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/wnan.1599

Nanocarriers in photodynamic therapy—in vitro and in vivo studies

Abstract The great promise of photodynamic therapy (PDT) has thrusted the rapid progress of developing highly effective photosensitizers (PS) in killing cancerous cells and bacteria. To mitigate the intrinsic limitations of the classical molecular photosensitizers, researchers have been looking into designing new generation of nanomaterial-based photosensitizers (nano-photosensitizers) with better photostability and higher singlet oxygen generation (SOG) efficiency, and ways of enhancing the performance of existing photosensitizers. In this paper, we review the recent development of nano-photosensitizers and nanoplasmonic strategies to enhance the SOG efficiency for better PDT performance. Firstly, we explain the mechanism of reactive oxygen species generation by classical photosensitizers, followed by a brief discussion on the commercially available photosensitizers and their limitations in PDT. We then introduce three types of new generation nano-photosensitizers that can effectively produce singlet oxygen molecules under visible light illumination, i.e., aggregation-induced emission nanodots, metal nanoclusters (&lt; 2 nm), and carbon dots. Different design approaches to synthesize these nano-photosensitizers were also discussed. To further enhance the SOG rate of nano-photosensitizers, plasmonic strategies on using different types of metal nanoparticles in both colloidal and planar metal-PS systems are reviewed. The key parameters that determine the metal-enhanced SOG (ME-SOG) efficiency and their underlined enhancement mechanism are discussed. Lastly, we highlight the future prospects of these nanoengineering strategies, and discuss how the future development in nanobiotechnology and theoretical simulation could accelerate the design of new photosensitizers and ME-SOG systems for highly effective image-guided photodynamic therapy. 

/pdf/emerging-strategies-in-enhancing-singlet-oxygen-generation-3fogfaeo.pdf

Emerging Strategies in Enhancing Singlet Oxygen Generation of Nano-Photosensitizers Toward Advanced Phototherapy

An assembly of hybrid hydrogel derived from Carbon Dot (CD), Protoporphyrin IX (PpIX) and DNA is reported here. PpIX and CD were covalently conjugated to 5′-phosphate termini of Cytosine (C) rich single strand DNA (ssDNA) separately. The CD-DNA-PpIX hybrid hydrogel was assembled through the formation of intercalated motif (i-motif) DNA network structure from CD-DNA and PpIX-DNA conjugates where CD act as crosslinkers in the hydrogel as well as energy donor to excite the photosensitizer (PS), PpIX. While hydrogel derived from only PpIX-DNA conjugate showed an inadequate sol-gel transition, the same could be precisely achieved from the CD-DNA-PpIX hybrid hydrogel by controlled pH adjustment. Distinct photophysical properties of CD and PpIX including fluorescence emission potentially enable tracking of the PS loading and hydrogel dissolution that was visually detectable under UV illumination. Reactive Oxygen Species (ROS) generation and subsequent killing of gram-positive bacteria (Staphylococcus aureus (S. aureus)) were observed following excitation of PpIX (acceptor) in the hybrid hydrogel either through energy transfer from CD or by direct irradiation of PpIX with visible light. Complete dissolution of hydrogel and sustained release of PpIX and subsequent ROS generation was achieved over 10–11 days that could kill S. aureus systematically. This study provides a promising strategy to address self-quenching and solubility of PS for its sustained release in Antimicrobial Photodynamic Therapy (A-PDT) applications through smart hydrogel formulation.

Carbon dot-DNA-protoporphyrin hybrid hydrogel for sustained photoinduced antimicrobial activity.

Gold nanoparticles with suitable properties are supreme therapeutic agents and provide effective signal enhancement in photodynamic therapy (PDT). In this study, protoporphyrin IX (PpIX) conjugated gold nanoparticles (GNPs) were prepared using covalent conjugation with cysteine as the adaptable linkage. The thiol group of cysteine was bound to the gold nanoparticles and also the formation of the amide linkage between PpIX and cysteine was confirmed using FT-IR. The spectroscopic characterizations (FT-IR and UV-vis) proved the formation of the PpIX conjugated gold nanoparticles. The reaction process was also followed using thin layer chromatography. Two different laser sources were used to activate the PpIX molecule in the ground state which was highly associated with the amount of singlet oxygen produced. Gold nanoparticles revealed a significant improvement in the singlet oxygen production of the PpIX molecule. The photocytotoxicity of the PpIX conjugated gold nanoparticles was also investigated using spermatogonial cells in vitro. The results confirm that the designed PpIX conjugated gold nanoparticles have provided a highly efficient agent for cellular photodynamic therapy.

Soheila Dehfuly

Papers

Efficient functionalization of gold nanoparticles using cysteine conjugated protoporphyrin IX for singlet oxygen production in vitro