Abstract

BackgroundThe increasing incidence of cancer and the search for more effective therapies with minimal collateral effects have prompted studies to find alternative new treatments. Among these, photodynamic therapy (PDT) has been proposed as a very promising new modality in cancer treatment with the lowest rates of side effects, revealing itself to be particularly successful when the photosensitizer is associated with nanoscaled carriers. This study aimed to design and develop a new formulation based on albumin nanospheres containing zinc-phthalocyanine tetrasulfonate (ZnPcS4-AN) for use in the PDT protocol and to investigate its antitumor activity in Swiss albino mice using the Ehrlich solid tumor as an experimental model for breast cancer.MethodsEhrlich tumor’s volume, histopathology and morphometry were used to assess the efficacy of intratumoral injection of ZnPcS4-AN in containing tumor aggressiveness and promoting its regression, while the toxicity of possible treatments was assessed by animal weight, morphological analysis of the liver and kidneys, hemogram, and serum levels of total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, creatinine and urea. In order to evaluate the efficacy of PDT, groups of animals treated with intratumoral injection of doxorubicin (Dox) were also investigated.ResultsIntratumoral injection of ZnPcS4-AN was found to be efficient in mediating PDT to refrain tumor aggressiveness and to induce its regression. Although tumor volume reduction was not significant, PDT induced a remarkable increase in the necrosis area seen in the tumor’s central region, as in other experimental groups, including tumor and Dox treated groups, but also in the tumor’s peripheral region. Further, PDT showed minimal adverse effects. Indeed, the use of ZnPcS4-AN in mediating PDT revealed anti-neoplastic activity similar to that obtained while using intratumoral Dox therapy.ConclusionsPDT mediated by the new formulation ZnPcS4-AN enhanced the inhibition of tumor growth while producing practically no adverse effects and thus emerges as a very promising nanotechnology-based strategy for solid cancer treatment.

Highlights

  • The increasing incidence of cancer and the search for more effective therapies with minimal collateral effects have prompted studies to find alternative new treatments

  • Aiming to potentialize the outcomes while using nanostructured drug delivery systems carrying phthalocyanines as photosensitizers, in the present study we report on the fabrication of a new albumin-based nanosphere containing zinc-phthalocyanine tetrasulfonate (ZnPcS4-AN) and further investigate its antitumor activity while mediating photodynamic therapy

  • ZnPcS4-AN characterization Scanning electron micrographs of the ZnPcS4-AN sample reveal the spherical shape (Figure 1) with smooth surface, as expected for this kind of system [26,27], whereas the analysis of the nanosphere size reveals that the employed preparation method produced nanospheres with average diameter of 320 nm

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Summary

Introduction

The increasing incidence of cancer and the search for more effective therapies with minimal collateral effects have prompted studies to find alternative new treatments. The increasing incidence of cancer and the search for the development of more effective therapies with minimal side effects have prompted studies to find alternative new treatments. PDT is currently being used in the clinical phase for treatment of several types of tumors [9,10] around the world [11,12,13,14] This therapy is effective in the treatment of accessible lesions, such as non-melanoma skin cancers and lesions with well-defined borders [2], it has been used outside oncology applications, including ophthalmology, dermatology, cardiology, virus inactivation, and blood purification [1]

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