Any variation in normal cellular function results in mitochondrial dysregulation that occurs in several diseases, including cancer. Such processes as oxidative stress, metabolism, signaling, and biogenesis play significant roles in cancer initiation and progression. Due to their central role in cellular metabolism, mitochondria are favorable therapeutic targets for the prevention and treatment of conditions like neurodegenerative diseases, diabetes, and cancer. Subcellular mitochondria-specific theranostic nanoformulations for simultaneous targeting, drug delivery, and imaging of these organelles are of immense interest in cancer therapy. It is a challenging task to cross multiple barriers to target mitochondria in diseased cells. To overcome these multiple barriers, several mitochondriotropic nanoformulations have been engineered for the transportation of mitochondria-specific drugs. These nanoformulations include liposomes, dendrimers, carbon nanotubes, polymeric nanoparticles (NPs), and inorganic NPs. These nanoformulations are made mitochondriotropic by conjugating them with moieties like dequalinium, Mito-Porter, triphenylphosphonium, and Mitochondria-penetrating peptides. Most of these nanoformulations are meticulously tailored to control their size, charge, shape, mitochondriotropic drug loading, and specific cell-membrane interactions. Recently, some novel mitochondria-selective antitumor compounds known as mitocans have shown high toxicity against cancer cells. These selective compounds form vicious oxidative stress and reactive oxygen species cycles within cancer cells and ultimately push them to cell death. Nanoformulations approved by the FDA and EMA for clinical applications in cancer patients include Doxil, NK105, and Abraxane. The novel use of these NPs still faces tremendous challenges and an immense amount of research is needed to understand the proper mechanisms of cancer progression and control by these NPs. Here in this review, we summarize current advancements and novel strategies of delivering different anticancer therapeutic agents to mitochondria with the help of various nanoformulations.

Introduction: Schistosomiasis is one of the most prevalent parasitic infections in developing countries. Although chemotherapy is one of the main strategies in controlling the disease, it is less effective in reversal of schistosome-induced pathology especially in the chronic and advanced stages of schistosomiasis. New strategies and prospective therapeutic agents with antifibrotic effects are needed. Eugenol has a wide anti-inflammatory effect. In the present study, we investigated the possible antischistosomal effect of eugenol on Schistosoma mansoni. Materials and methods: The murine model of S. mansoni was established in three groups of adult male Balb-c mice; group I (infected non-treated group) and groups II and III (infected groups) treated orally with eugenol and praziquantel (PZQ), respectively. The expression of the sensitive immunohistochemical marker α-smooth muscle actin (α-SMA) in schistosome-infected tissues was determined. In addition, parasitological, biochemical, and histological parameters that reflect disease severity and morbidity were examined. Results: Eugenol treatment showed significant reduction in total worm burden by 19.2%; however, the oogram pattern showed no marked difference compared to that of the PZQ group. Yet, eugenol significantly reduced the serum levels of hepatic enzymes: aspartate aminotransferase and alanine aminotransferase. Histopathological examination revealed a significant reduction in both numbers and diameters of hepatic granulomata, which was consistent with reduction in collagen fiber deposition. Additionally, the antifibrotic effect of eugenol was validated by its considerable reduction in the expression of the sensitive marker α-SMA in both eugenol- and PZQ-treated groups. Conclusion: Although eugenol could not totally eradicate adults of S. mansoni, the significant amelioration of liver enzymes and hepatic fibrosis potentiate eugenol’s role as a promising antifibrotic and a complementary antischistosomal agent.

Giardiasis is a major diarrheal disease affecting approximately 2.5 million children annually in developing countries. Several studies have reported the resistance of Giardia lamblia (G. lamblia) to multiple drugs. Therefore, identifying an effective drug for giardiasis is a necessity. This study examined the antiparasitic effect of Punica granatum (pomegranate) and evaluated its therapeutic efficacy in rats infected with G. lamblia. In vitro study showed high efficacy of pomegranate peel ethanolic extract in killing G. lamblia cysts as demonstrated by eosin vital staining. We showed that treating infected rats with pomegranate extract resulted in a marked reduction in the mean number of G. lamblia cysts and trophozoites in feces and intestine respectively. Interestingly, the number of G. lamblia trophozoites and cysts were significantly lower in the pomegranate extract-treated group compared to the metronidazole-positive control group. Moreover, pomegranate extract treatment significantly induced nitric oxide (NO) and reduced serum IL-6 and TNF-α, compared to infected untreated rats. Histological and scanning electron microscopy (SEM) examination of the jejunum and duodenum of pomegranate extract-treated animals confirmed the antiparasitic effect of the extract, and demonstrated the restoration of villi structure with reduction of villi atrophy, decreased infiltration of lymphocytes, and protection of intestinal cells from apoptotic cell death. In conclusion, our data show that the pomegranate peel extract is effective in controlling G. lamblia infections, which suggests that it could be a viable treatment option for giardiasis.

Neurocysticercosis, the most common type of neuroparasitosis, is a condition in which the central nervous system (CNS) is infested with the pork tapeworm Taenia solium cysticercosis’ larvae. Neurocysticercosis is the most widespread parasitic CNS disease worldwide, affecting more than 50 million individuals. As neurocysticercosis is prevalent in developing countries, the growing number of migrants and travelers increases prevalence in developed countries. Possible neuropsychiatric manifestations are depression, cognitive dysfunction, dementia, and visual hallucinations. Depending on the cysts’ location in the CNS, focal neurology or psychiatric symptoms manifest. The diagnosis of neurocysticercosis is based on neuroimaging and serology. The correlation between specific symptoms and the cyst’s location might help better understand psychiatric disorders’ pathophysiology. Nonetheless, the exact prevalence of neurocysticercosis is seldom reported in patients with psychiatric disorders, which may be due to the lack of imaging availability in developing countries with a high prevalence.

Background: Although, approximately 30% of the world’s population is estimated to be infected with Toxoplasma gondii (T. gondii) with serious manifestations in immunocompromised patients and pregnant females, the available treatment options for toxoplasmosis are limited with serious side effects. Therefore, it is of great importance to identify novel potent, well tolerated candidates for treatment of toxoplasmosis. The present study aimed to evaluate the effect of Zinc oxide nanoparticles (ZnO NPs) synthesized using Zingiber officinale against acute toxoplasmosis in experimentally infected mice. Methods: The ethanolic extract of ginger was used to prepare ZnO NPs. The produced ZnO NPs were characterized in terms of structure and morphology using Fourier Transformed Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), UV- spectroscopy and scanning electron microscopy (SEM). The prepared formula was used in treatment of T. gondii RH virulent strain. Forty animals were divided into four groups, with ten mice per group. The first group was the uninfected, control group. The second group was infected but untreated. The third and the fourth groups received ZnO NPs and Spiramycin orally in a dose of 10 mg/kg and 200 mg/kg/day respectively. The effect of the used formulas on the animals survival rate, parasite burden, liver enzymes -including Alanine transaminase (ALT) and aspartate transaminase (AST)-, nitric oxide (NO) and Catalase antioxidant enzyme (CAT) activity was measured. Moreover, the effect of treatment on histopathological alterations associated with toxoplasmosis was examined. Results: Mice treated with ZnO NPs showed the longest survival time with significant reduction in the parasite load in the livers and peritoneal fluids of the same group. Moreover, ZnO NPs treatment was associated with a significant reduction in the level of liver enzymes (ALT, AST) and NO and a significant increase in the antioxidant activity of CAT enzyme. SEM examination of tachyzoites from the peritoneal fluid showed marked distortion of T. gondii tachyzoites isolated from mice treated with ZnO NPs in comparison to untreated group. T. gondii induced histopathological alterations in the liver and brain were reversed by ZnO NPs treatment with restoration of normal tissue morphology. Conclusion: The produced formula showed a good therapeutic potential in treatment of murine toxoplasmosis as demonstrated by prolonged survival rate, reduced parasite burden, improved T. gondii associated liver injury and histopathological alterations. Thus, we assume that the protective effect observed in the current research is attributed to the antioxidant capability of NPs. Based on the results obtained from the current work, we suggest greenly produced ZnO NPs as a chemotherapeutic agent with good therapeutic potential and high levels of safety in the treatment of toxoplasmosis.

Acinetobacter baumannii has recently been increasing as an aggressive pathogen in immunocompromised persons. In the present study, we determined the in vitro antibacterial and anti-biofilm activity of thymoquinone (TQ) against A. baumannii. A liposomal formulation of TQ (Lip-TQ) was prepared and its therapeutic potential was investigated in the treatment of A. baumannii infection in immunocompromised mice. Leukopenia was induced in mice by injecting cyclophosphamide (CYP) at a dose of 200 mg/kg and the leukopenic mice were infected with 1 × 10⁶ CFUs of A. baumannii. The effectiveness of free TQ or Lip-TQ against A. baumannii infection was assessed by analyzing the survival rate and bacterial burden. Moreover, the efficacy of Lip-TQ was also studied by examining the systemic inflammatory markers and the histological changes in the lung tissues. The results showed that the mice in the group treated with Lip-TQ at a dose of 10 mg/kg exhibited a 60% survival rate on day 40 post-infection, whereas all the mice treated with free TQ at the same dose died within this duration. Likewise, the lowest bacterial burden was found in the lung tissue of mice treated with Lip-TQ (10 mg/kg). Besides, Lip-TQ treatment remarkably alleviated the infection-associated inflammation, oxidative stress, and histological changes in the lung tissues. Based on the findings of the present study, we recommend considering Lip-TQ as a valuable therapeutic formulation in the treatment of A. baumannii-associated pneumonia in immunocompromised subjects.