Therapies and Vaccines Based on Nanoparticles for the Treatment of Systemic Fungal Infections

Brenda Kischkel,Joshua D Nosanchuk,Luiz R Travassos,Carlos P Taborda,Samuel R Santos,Suélen A Rossi

doi:10.3389/fcimb.2020.00463

Abstract

Treatment modalities for systemic mycoses are still limited. Currently, the main antifungal therapeutics include polyenes, azoles, and echinocandins. However, even in the setting of appropriate administration of antifungals, mortality rates remain unacceptably high. Moreover, antifungal therapy is expensive, treatment periods can range from weeks to years, and toxicity is also a serious concern. In recent years, the increased number of immunocompromised individuals has contributed to the high global incidence of systemic fungal infections. Given the high morbidity and mortality rates, the complexity of treatment strategies, drug toxicity, and the worldwide burden of disease, there is a need for new and efficient therapeutic means to combat invasive mycoses. One promising avenue that is actively being pursued is nanotechnology, to develop new antifungal therapies and efficient vaccines, since it allows for a targeted delivery of drugs and antigens, which can reduce toxicity and treatment costs. The goal of this review is to discuss studies using nanoparticles to develop new therapeutic options, including vaccination methods, to combat systemic mycoses caused by Candida sp., Cryptococcus sp., Paracoccidioides sp., Histoplasma sp., Coccidioides sp., and Aspergillus sp., in addition to providing important information on the use of different types of nanoparticles, nanocarriers and their corresponding mechanisms of action.

Highlights

Fungal diseases are broadly classified according to the degree of interactions between the pathogen and the host tissue in superficial, subcutaneous, and systemic infections (Tiew et al, 2020)
The results showed that only the administration of ADS1 was able to confer protection against infection in mice, with a high production of specific antibodies that increased fungal phagocytosis
The results showed that the formulation exhibited good in vitro activity against P. brasiliensis and P. lutzii (0.24 and 0.49 mg/L, respectively), low toxicity in pulmonary fibroblasts (>250 mg/L) and zebrafish embryos (>125 mg/L)

Summary

Introduction

Fungal diseases are broadly classified according to the degree of interactions between the pathogen and the host tissue in superficial, subcutaneous, and systemic infections (Tiew et al, 2020). Infections of endogenous origin caused by pathogens such as Candida albicans can occur (Colombo et al, 2017; Rautemaa-Richardson and Richardson, 2017). In the case of endemic mycoses, immunocompetent individuals dwelling in endemic areas may develop severe disease following inhalation of fungal particles, associated or not to a competent immune response (Edwards et al, 2013). The main species that cause endemic mycoses are Blastomyces dermatitidis, Coccidioides immitis and Coccidioides posadasii, Histoplasma capsulatum, Paracoccidioides, P. brasiliensis and P. lutzii, Sporothrix, primarily S. brasiliensis and S. schenckii, and Talaromyces marneffei (Brown et al, 2012; Limper et al, 2017)

Objectives

Findings

Conclusion