Sequential Photodynamic Therapy with Phthalocyanine Encapsulated Chitosan-Tripolyphosphate Nanoparticles and Flucytosine Treatment against Candida tropicalis

Abstract

Antibiotic resistance has become a crisis. Candida tropicalis (C. tropicalis) is one of the most highly virulent and drug-resistant pathogens. An alternative antimicrobial therapy to eradicate C. tropicalis effectively, without the risk of developing drug-resistance, is needed. Photodynamic therapy (PDT) is an alternative therapy that does not carry the risk of undesired drug resistance. To target the pathogens and to enhance the cellular penetration of the applied photosensitizer, we fabricated cationic chitosan/tripolyphosphate nanoparticles to encapsulate phthalocyanine. Our strategy promotes the uptake of phthalocyanine four-fold. This enhanced PDT can effectively inhibit planktonic C. tropicalis, such that only ~20% of C. tropicalis in the test survived; but it has a limited ability to inhibit adherent C. tropicalis. Further tests with adherent C. tropicalis indicated that sequential treatment with PDT and flucytosine significantly eliminates pseudohyphae and yeast-like C. tropicalis cells. The cell viability is only ~10% after this sequential treatment. This study provides evidence of an effective therapy against drug resistant C. tropicalis, and this strategy can be potentially applied to other pathogens.

Porphyrin-Loaded Lignin Nanoparticles Against Bacteria: A Photodynamic Antimicrobial Chemotherapy Application

“…In parallel, organic matrices (e.g., cellulose, chitosan, cyclodextrin) have been used for the transport and encapsulation of small molecules, with some examples of conjugating photosensitizers, enabling bacterial eradication and, in some cases, demonstrating a synergistic effect with the organic matrix ( Hsieh et al, 2019 ; Maldonado-Carmona et al, 2020 ). In this regard, an organic matrix that has been neglected is lignin.…”

Photodynamic Therapy Review: Principles, Photosensitizers, Applications, and Future Directions

“…Light applied intravenously can be a solution during the clinical treatment of infections. Very recently, the use of the PDT procedure to treat patients with COVID-19 has also been discussed [ 8 , 57 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 ].…”

Photosensitizers Mediated Photodynamic Inactivation against Fungi

“…Scientists also compared the effectiveness of PACT mediated with pcs against planktonic and biofilm forms of pathogens. Hsieh et al performed research on the use of PACT to target C. tropicalis and to improve the cellular penetration of the tested pc PS [229]. They prepared cationic chitosan/tripolyphosphate NPs to encapsulate pc which enhanced its uptake four-fold.…”

“…PACT effectively eradicated 80% of planktonic C. tropicalis. However, to eliminate adherent C. tropicalis, sequential treatment with PACT and flucytosine had to be implemented to eradicate pseudohyphae and yeast-like C. tropicalis cells [229]. Mantareva et al synthesized water-soluble pc complexes of silicon (39, Figure 10) and germanium (40, Figure 10) to test their photodynamic efficacy against C. albicans both in planktonic and biofilm form [230].…”