Monica Camerin

The in vivo efficacy of phthalocyanine–nanoparticle conjugates for the photodynamic therapy of amelanotic melanoma

The efficiency of a Zn(II)-phthalocyanine disulphide (C11Pc), a compound with both phthalocyanine units bearing seven hexyl chains and a sulphur terminated C11 chain, as a photodynamic therapy (PDT) agent was investigated in C57 mice bearing a sub-cutaneously transplanted amelanotic melanoma. The phthalocyanine was intravenously injected at a dose of 1.5 micromol/kg body weight either free or bound to gold nanoparticles, using a Cremophor emulsion as a delivery vehicle. Biodistribution studies at selected post-injection times showed that the nanoparticle-associated C11Pc was recovered in significantly larger amounts from all the examined tissues and the serum and yielded a greater selectivity of tumour targeting: thus, the ratio between the amount of phthalocyanine recovered from the amelanotic melanoma and the skin (peritumoural tissue) increased from 2.3 to 5.5 from the free to the gold nanoparticle-bound C11Pc at 24 h after injection. PDT studies with the C11Pc-loaded amelanotic melanoma showed a markedly more significant response of the tumour in the mice that had received the nanoparticle-bound photosensitiser; the PDT effect was especially extensive if the irradiation was performed at 3h after C11Pc injection when large phthalocyanine amounts were still present in the serum. This suggests that the PDT promoted by C11Pc predominantly acts via vascular damage at least in this specific animal model. This hypothesis was fully confirmed by electron microscopy observations of tumour specimens obtained at different times after the end of PDT, showing an extensive damage of the blood capillaries and the endothelial cells.

Metallo‐naphthalocyanines as photothermal sensitisers for experimental tumours: In Vitro and in vivo studies

Photothermal sensitisation has been recently proposed as a novel approach for the treatment of solid tumours through the development of a therapeutic modality named photothermal therapy (PTT). The technique involves the use of high power pulsed laser irradiation and photosensitising agents with especially short lifetime (in the subnanosecond range) in the electronically excited states. This study aims to investigate the molecular features of the photosensitiser which optimise the photothermal activity.

Polymer nanoparticles with electrostatically loaded multicargo for combined cancer phototherapy

We have developed a multifunctional polymer-based nanoplatform for bimodal cancer phototherapy. It was achieved by electrostatic entangling of two anionic photoactivable components, a commercial porphyrin and a tailored nitro-aniline derivative, within the cationic shell of polymeric nanoparticles (NPs) based on polymethyl methacrylate. The combination of steady-state and time-resolved spectroscopic and photochemical techniques shows that the two photoresponsive agents do not interfere with each other while being in close proximity in the same polymeric scaffold and can thus operate in parallel under the exclusive control of light stimuli. Specifically, visible light triggers satisfactory red fluorescence emission and generation of singlet oxygen (1O2) from one component and release of nitric oxide (NO) from the other. Fluorescence microscopy analysis provides unambiguous evidence for the internalization of the NPs within B78H1 melanoma cells, where they induce amplified mortality due to a combinatory effect of the two photogenerated cytotoxic species.

Chapter 1:Antimicrobial Photodynamic Therapy: Basic Principles

PDT of infectious diseases of microbial origin is based on the property of selected photosensitising agents, especially those characterized by the presence of positively charged functional groups, to readily bind with the outer wall of bacterial, fungal and protozoan cells; once activated by irradiation with visible light, the photosensitisers generate reactive oxygen species which induce the irreversible modification of specific constituents of the wall. The consequent enhanced permeability of the wall allows sufficiently large doses of the photosensitiser to penetrate to the cytoplasmic membrane. The photoprocess then involves a number of endocellular activities (e.g., enzymic catalysis, metabolic pathways) whose integrity is critical for cell survival. The genetic material is generally involved in the late stage of the photoprocess, which minimizes the probability of inducing mutagenic processes. A suitable choice of the irradiation protocol usually leads to an extensive killing of microbial pathogens with no or minimal damage to host tissues. PDT differs from other usually adopted therapeutic modalities for the broad spectrum of action, the efficacy against antibiotic resistant cells, and the lack of selection of photoresistant strains.

Photodynamic Therapy: A Novel Promising Approach for the Treatment of Spontaneous Microbial Infections in Pet Animals

Photodynamic therapy with full spectrum visible light and porphyrin-type photosensitisers appears to efficiently induce the inactivation of a broad spectrum of microbial pathogens, including antibiotic-resistant strains, without in turn promoting the selection of PDT-resistant species. Application of this therapeutic modality to the treatment of spontaneously developed infections in dogs resulted in a very efficient healing of wounds with an extensive drop in the population of pathogens. The treatment appeared to be applicable for both mycotic and bacterial infections and was devoid of detectable undesired side effects. No significant differences in efficacy was observed whether a porphyrin, chlorin, or phthalocyanine photosensitising agent was used in spite of strong differences in the light absorption spectrum among the three tetrapyrrole derivatives.