Combination of selol nanocapsules and magnetic hyperthermia hinders breast tumor growth in aged mice after a short-time treatment.

Short time treatment with reduced dosages of selol-loaded PLGA nanocapsules (NcSel) combined with magnetic hyperthermia (MHT) is evaluated in aged Erhlich tumor-bearing mice. Clinical, hematological, biochemical, genotoxic and histopathological parameters are assessed during 7 d treatment with NcSel and MHT, separately or combined. The time evolution of the tumor volume is successfully modeled using the logistic mathematical model. The combined therapy comprising NcSel and MHT is able to hinder primary tumor growth and a case of complete tumor remission is recorded. Moreover, no metastasis was diagnosed and the adverse effects are negligible. NcSel plus MHT may represent an effective and safe alternative to cancer control in aged patients. Future clinical trials are encouraged.

A New Endoplasmic Reticulum (ER)-Targeting Fluorescent Probe for the Imaging of Cysteine in Living Cells.

Cysteine (Cys) is an important endogenous amino acid and plays critical physiological roles in living systems. Herein, an endoplasmic reticulum (ER)-targeting fluorescent probe (FER-Cys) was designed and prepared for imaging of Cys in living cells. The probe FER-Cys consists of a fluorescein framework as the fluorescent platform, acrylate group as the response site for the selective recognition of Cys, and ER-specific p-toluenesulfonamide fragment. After the response of probe FER-Cys to Cys, a turn-on fluorescence signal at 546 nm could be detected obviously. The probe FER-Cys further shows desirable selectivity to Cys. Finally, the probe FER-Cys was proven to selectively detect Cys in live cells and successfully image the changes of Cys level in the cell models of H2O2-induced redox imbalance.

Clinical treatment of intra-epithelia cervical neoplasia with photodynamic therapy.

OBJECTIVES: This clinical study was developed to primarily evaluate the Complete Cytopathological Response Rate of Cervical Intraepithelial Neoplasms to PDT using chitosan nanocapsules containing Chlorocyan-aluminum phthalocyanine as a photoactive agent. Analyses of the Free Recurrence Interval, toxicity profile (immediate and late), and complications (immediate and late), were secondarily analyzed. METHODS: This study was previously approved by the National Council of Ethics in Research of Brazil (CONEP), on May 28, 2014, under case number 19182113.4.0000.5009. On the surface of the cervix of each selected patient was applied one mL of the formulated gel, and after 30 min, the light was applied. Reports or the identification of adverse effects and/or complications were observed in follow-up visits, in addition to the collection of cervical oncotic cytology. RESULTS: Out of the total group, 11 (91.7%) primarily treated patients evolved with negative cervical oncotic cytology as soon as in the first evaluation following treatment, and one did not achieve any therapeutic benefit, even after reapplication. Two patients with initially positive response presented cytological recurrence determined by histopathology. A new round of PDT was developed, and both evolved with cytological remission three weeks later, remaining negative until the last follow-up. No important side effects were observed in all the patients. CONCLUSIONS: Our trial demonstrates that treatment of CIN 1 and 2 lesions using our PDT formulation is feasible and safe. Large randomized clinical trials are required to establish efficacy.

New Bis copper complex ((Z) -4 - ((4-chlorophenyl) amino) -4-oxobut-2-enoyl) oxy): Cytotoxicity in 4T1 cells and their toxicogenic potential in Swiss mice.

Copper (II) complexes are promising in the development of new synthetic models for cancer treatment. In this context, we synthesized a new copper complex containing the pharmacophore group 1,4-dioxo-2-butenyl, the Bis(((Z)-4-((4-chlorophenyl) amino)-4-oxobut-2-enoyl)oxy) copper compound and we evaluated its antitumor activity in 4 T1 murine mammary adenocarcinoma cells and their toxicogenic effect in Swiss mice. The compound demonstrated cytotoxicity and genotoxicity to 4 T1 cells, and after cell cycle arrest in G1, which occurred by the increase in ATM and p21 expression, it induced the cells to apoptosis by increasing BAX and caspase-7. In vivo the compound was genotoxic in mice but did not show permanent damage, observed by the absence of increased micronucleus frequency, and did not induce changes in the biometric parameters of the animals. These results indicate that the new copper complex, described firstly in this work, presents therapeutic potential for breast cancer.

In vitro exposure of bull sperm cells to DMSA-coated maghemite nanoparticles does not affect cell functionality or structure.

Magnetic nanoparticles can be used in different areas of biology. It is therefore important to know the effects of such nanomaterials on germline cells as they may traverse the blood-testis barrier. This work aimed to evaluate the response of bull sperm after exposure to a magnetic fluid containing DMSA-coated maghemite nanoparticles (MNP-DMSA) in order to determine nanotoxicity. Bull sperm was incubated with MNP-DMSA at final concentrations of 0.06, 0.03 or 0.015 mg Fe/mL. Sperm kinetics, plasma membrane integrity and acrosome reaction were evaluated over a 4 h incubation period. The sperm cells were also evaluated by transmission electron microscopy. Exposure of bull sperm to MNP-DMSA did not affect sperm kinetics or integrity. Neither ultrastructural damage of sperm cells nor uptake of nanoparticles by the spermatozoa was observed. In conclusion, MNP-DMSA does not affect sperm function or structure under the conditions tested.

Nanographene oxide-methylene blue as phototherapies platform for breast tumor ablation and metastasis prevention in a syngeneic orthotopic murine model.

BACKGROUND: In the photodynamic therapy (PDT), the photosensitizer absorbs light and transfers the energy of the excited state to the oxygen in the cell environment producing reactive oxygen species (ROS), that in its turn, may cause cell damage. In the photothermal therapy (PTT), light also is responsible for activating the photothermal agent, which converts the absorbed energy in heat. Graphene oxide is a carbon-based material that presents photothermal activity. Its physical properties allow the association with the photosensitizer methylene blue and consequently the production of ROS when submitted to light irradiation. Therefore, the association between nanographene oxide and methylene blue could represent a strategy to enhance therapeutic actions. In this work, we report the nanographene oxide-methylene blue platform (NanoGO-MB) used to promote tumor ablation in combination with photodynamic and photothermal therapies against a syngeneic orthotopic murine breast cancer model. RESULTS: In vitro, NanoGO-MB presented 50% of the reactive oxygen species production compared to the free MB after LED light irradiation, and a temperature increase of ~ 40 °C followed by laser irradiation. On cells, the ROS production by the nanoplatform displayed higher values in tumor than normal cells. In vivo assays demonstrated a synergistic effect obtained by the combined PDT/PTT therapies using NanoGO-MB, which promoted complete tumor ablation in 5/5 animals. Up to 30 days after the last treatment, there was no tumor regrowth compared with only PDT or PTT groups, which displayed tumoral bioluminescence 63-fold higher than the combined treatment group. Histological studies confirmed that the combined therapies were able to prevent tumor regrowth and liver, lung and spleen metastasis. In addition, low systemic toxicity was observed in pathologic examinations of liver, spleen, lungs, and kidneys. CONCLUSIONS: The treatment with combined PDT/PTT therapies using NanoGO-MB induced more toxicity on breast carcinoma cells than on normal cells. In vivo, the combined therapies promoted complete tumor ablation and metastasis prevention while only PDT or PTT were unable to stop tumor development. The results show the potential of NanoGO-MB in combination with the phototherapies in the treatment of the breast cancer and metastasis prevention.

Decoration of a Poly(methyl vinyl ether-co-maleic anhydride)-Shelled Selol Nanocapsule with Folic Acid Increases Its Activity Against Different Cancer Cell Lines In Vitro.

Due to the low therapeutic index of different chemotherapeutic drugs used for cancer treatment, the development of new anticancer drugs remains an intense field of research. A recently developed mixture of selenitetriacylglycerides, selol, was shown to be active against different cancer cells in vitro. As this compound is highly hydrophobic, it was encapsulated, in a previous study, into poly(methyl vinyl ether-co-maleic anhydride)-shelled nanocapsules in order to improve its dispersibility in aqueous media. Following this line of research, the present report aimed at enhancing the In Vitro activity of the selol nanocapsules against cancerous cells by decorating their surface with folic acid. It is known that several cancer cells overexpress folate receptors. Stable folic acid-decorated selol nanocapsules (SNP-FA) were obtained, which showed to be spherical, with a hydro-dynamic diameter of 364 nm, and zeta potential of -24 mV. In comparison to non-decorated selol nanocapsules, SNP-FA presented higher activity against 4T1, MCF-7 and HeLa cells. Moreover, the decoration of the nanocapsules did not alter their toxicity towards fibroblasts, NIH-3T3 cells. These results show that the decoration with folic acid increased the toxicity of selol nanocapsules to cancer cells. These nanocapsules, besides enabling to disperse selol in an aqueous medium, increased the toxicity of this drug In Vitro, and may be useful to treat cancer in vivo, potentially increasing the specificity of selol towards cancer cells.

Identification of a novel small-molecule Keap1-Nrf2 PPI inhibitor with cytoprotective effects on LPS-induced cardiomyopathy.

A new Keap1-Nrf2 protein-protein interaction (PPI) inhibitor ZJ01 was identified from our compound library by fluorescence polarization assay, surface plasmon resonance, molecular docking and molecular dynamics simulation. ZJ01 could in vitro trigger Nrf2 nuclear translocation, subsequently resulting in increased mRNA levels of Nrf2 target genes HO-1 and NQO1. Meanwhile, ZJ01 suppressed LPS-induced production of ROS and the mRNA levels of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 in H9c2 cardiac cells. Moreover, in an in vivo mouse model of septic cardiomyopathy induced by intraperitoneal injection of lipopolysaccharide, ZJ01 demonstrated a cytoprotective effect, upregulated Nrf2 protein nuclear accumulation, and remarkably suppressed the abovementioned cytokine levels in cardiomyocytes. The results presented herein provided a novel chemotype for the development of direct Keap1-Nrf2 PPI inhibitors and suggested that compound ZJ01 is a promising drug lead for septic cardiomyopathy treatment. ZJ01 was identified as a new Keap1-Nrf2 PPI inhibitor and drug lead for septic cardiomyopathy treatment by in vitro and in vivo experiments.

Design and synthesis of pregnenolone/2-cyanoacryloyl conjugates with dual NF-κB inhibitory and anti-proliferative activities.

Twenty-five novel pregnenolone/2-cyanoacryloyl conjugates (6-30) were designed and prepared, with the aim of developing novel anticancer drugs with dual NF-κB inhibitory and anti-proliferative activities. Compounds 22 and 27-30 showed inhibition against TNF-α-induced NF-κB activation in luciferase assay, which was confirmed by Western blotting. Among them, compound 30 showed potent NF-κB inhibitory activity (IC50=2.5µM) and anti-proliferative against MCF-7, A549, H157, and HL-60 cell lines (IC50=6.5-36.2µM). The present study indicated that pregnenolone/2-cyanoacryloyl conjugate I can server asa novel scaffold for developing NF-κB inhibitors and anti-proliferative agents in cancer chemotherapy.

Synthesis and evaluation of novel 1,2,3-triazole-based acetylcholinesterase inhibitors with neuroprotective activity.

A series of new 1,2,3-triazole derivatives were synthesized and evaluated for anticholinesterase and neuroprotective activities. Some synthetic derivatives, especially compound 32, exhibited improved acetylcholinesterase (AChE) inhibitory activity by comparison with the hit 1, high selectivity toward AChE over butyrylcholinesterase (BuChE), and suitable in vitro neuroprotective effect against amyloid-ß25-35 (Aß25-35)-induced neurotoxicity in SH-SY5Y cells. Furthermore, these molecules have desired physicochemical properties in the range of CNS drugs and showed no cytotoxicity against two normal cells, including human keratinocytes HaCaT and murine fibroblasts NIH-3T3. The preliminary bioassay results and docking study indicated that compound 32 might be a promising lead compound with dual action for the treatment of Alzheimer's disease.

The lipidome, genotoxicity, hematotoxicity and antioxidant properties of andiroba oil from the Brazilian Amazon.

Andirobeira is an Amazonian tree, the seeds of which produce a commercially valuable oil that is used in folk medicine and in the cosmetic industry. Andiroba oil contains components with anti-inflammatory, cicatrizing and insect-repellant actions. However, virtually nothing is known of the safety of this oil for humans. The aim of this work was therefore to investigate the hematotoxicity, genotoxicity and mutagenicity of andiroba oil using the comet and micronucleus assays, and to assess its antioxidant properties and lipidome as a means of addressing safety issues. For the experiments, andiroba oil was administered by gavage for 14 consecutive days in nulliparous female Swiss mice randomly distributed in four groups: negative control and three doses of oil (500, 1000 and 2000 mg/kg/day). These doses were chosen based on recommendations of the OECD guideline no. 474 (1997). GC/MS was used to investigate the free fatty acid, cholesterol and triterpene content of andiroba oil in a lipidomic analysis. No clinical or behavioral alterations were observed throughout the period of treatment, and exposure to andiroba oil at the doses and conditions used here did not result in hematotoxic, genotoxic or mutagenic effects. Tests in vitro showed that oil sample 3 from southwestern of Brazilian Amazon had a high antioxidant capacity that may protect biological systems from oxidative stress, although this activity remains to be demonstrated in vivo.

Antitumor activity and systemic effects of PVM/MA-shelled selol nanocapsules in lung adenocarcinoma-bearing mice.

Selol is a semi-synthetic compound containing selenite that is effective against cancerous cells and safer for clinical applications in comparison with other inorganic forms of selenite. Recently, we have developed a formulation of poly(methyl vinyl ether-co-maleic anhydride)-shelled selol nanocapsules (SPN), which reduced the proliferative activity of lung adenocarcinoma cells and presented little deleterious effects on normal cells in in vitro studies. In this study, we report on the antitumor activity and systemic effects induced by this formulation in chemically induced lung adenocarcinoma-bearing mice. The in vivo antitumor activity of the SPN was verified by macroscopic quantification, immunohistochemistry and morphological analyses. Toxicity analyses were performed by evaluations of the kidney, liver, and spleen; analyses of hemogram and plasma levels of alanine aminotransferase, aspartate transaminase, urea, and creatinine; and DNA fragmentation and cell cycle activity of the bone marrow cells. Furthermore, we investigated the potential of the SPN formulation to cause hemolysis, activate the complement system, provoke an inflammatory response and change the conformation of the plasma proteins. Our results showed that the SPN reduced the area of the surface tumor nodules but not the total number of tumor nodules. The biochemical and hematological findings were suggestive of the low systemic toxicity of the SPN formulation. The surface properties of the selol nanocapsules point to characteristics that are consistent with the treatment of the tumors in vivo: low hemolytic activity, weak inflammatory reaction with no activation of the complement system, and mild or absent conformational changes of the plasma proteins. In conclusion, this report suggests that the SPN formulation investigated herein exhibits anti-tumoral effects against lung adenocarcinoma in vivo and is associated with low systemic toxicity and high biocompatibility.

Characterization and Biological Activities of Ocellatin Peptides from the Skin Secretion of the Frog Leptodactylus pustulatus.

Eight new peptides were isolated from the skin secretion of the frog Leptodactylus pustulatus and their amino acid sequences determined by de novo sequencing and by cDNA cloning. Structural similarities between them and other antimicrobial peptides from the skin secretion of Leptodactylus genus frogs were found. Ocellatins-PT1 to -PT5 (25 amino acid residues) are amidated at the C-terminus, while ocellatins-PT6 to -PT8 (32 amino acid residues) have free carboxylates. Antimicrobial activity, hemolytic tests, and cytotoxicity against a murine fibroblast cell line were investigated. All peptides, except for ocellatin-PT2, have antimicrobial activity against at least one Gram-negative strain. Ocellatin-PT8 inhibited the growth of Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Salmonella choleraesuis strains with MICs in the 60-240 µM range. No significant effect was observed in human erythrocytes and in a murine fibroblast cell line after exposure to the peptides at MICs. A comparison between sequences obtained by both direct HPLC-MS de novo sequencing and cDNA cloning demonstrates the secretion of mature peptides derived from a pre-pro-peptide structure.

Aluminium-phthalocyanine chloride nanoemulsions for anticancer photodynamic therapy: Development and in vitro activity against monolayers and spheroids of human mammary adenocarcinoma MCF-7 cells.

BACKGROUND: Photodynamic therapy (PDT) combines light, molecular oxygen and a photosensitizer to induce oxidative stress in target cells. Certain hydrophobic photosensitizers, such as aluminium-phthalocyanine chloride (AlPc), have significant potential for antitumor PDT applications. However, hydrophobic molecules often require drug-delivery systems, such as nanostructures, to improve their pharmacokinetic properties and to prevent aggregation, which has a quenching effect on the photoemission properties in aqueous media. As a result, this work aims to develop and test the efficacy of an AlPc in the form of a nanoemulsion to enable its use in anticancer PDT. RESULTS: The nanoemulsion was developed using castor oil and Cremophor ELP®, and a monodisperse population of nanodroplets with a hydrodynamic diameter of approximately 25 nm was obtained. While free AlPc failed to show significant activity against human breast adenocarcinoma MCF-7 cells in an in vitro PDT assay, the AlPc in the nanoemulsion showed intense photodynamic activity. Photoactivated AlPc exhibited a 50 % cytotoxicity concentration (CC50) of 6.0 nM when applied to MCF-7 cell monolayers and exerted a powerful cytotoxic effect on MCF-7 cell spheroids. CONCLUSION: Through the use of spontaneous emulsification, a stable AlPc nanoemulsion was developed that exhibits strong in vitro photodynamic activity on cancer cells.

PVM/MA-shelled selol nanocapsules promote cell cycle arrest in A549 lung adenocarcinoma cells.

BACKGROUND: Selol is an oily mixture of selenitetriacylglycerides that was obtained as a semi-synthetic compound containing selenite. Selol is effective against cancerous cells and less toxic to normal cells compared with inorganic forms of selenite. However, Selol's hydrophobicity hinders its administration in vivo. Therefore, the present study aimed to produce a formulation of Selol nanocapsules (SPN) and to test its effectiveness against pulmonary adenocarcinoma cells (A549). RESULTS: Nanocapsules were produced through an interfacial nanoprecipitation method. The polymer shell was composed of poly(methyl vinyl ether-co-maleic anhydride) (PVM/MA) copolymer. The obtained nanocapsules were monodisperse and stable. Both free Selol (S) and SPN reduced the viability of A549 cells, whereas S induced a greater reduction in non-tumor cell viability than SPN. The suppressor effect of SPN was primarily associated to the G2/M arrest of the cell cycle, as was corroborated by the down-regulations of the CCNB1 and CDC25C genes. Apoptosis and necrosis were induced by Selol in a discrete percentage of A549 cells. SPN also increased the production of reactive oxygen species, leading to oxidative cellular damage and to the overexpression of the GPX1, CYP1A1, BAX and BCL2 genes. CONCLUSIONS: This study presents a stable formulation of PVM/MA-shelled Selol nanocapsules and provides the first demonstration that Selol promotes G2/M arrest in cancerous cells.

Metallic-based phthalocyanine nanoemulsions for photodynamic purging of ovarian tissue in leukemia patients.

For cancer patients with a high risk of ovarian tissue metastasis, ovarian autotransplantation is not advised due to the potential spread of malignant cells. Ex vivo purging of ovarian fragments may offer a more suitable alternative for fertility restoration. Eradicating malignant cells should be done selectively without affecting follicles or ovarian stromal cells (SCs). As a clinically licensed method, photodynamic therapy (PDT) is a minimally invasive treatment to destroy cancer cells. This study evaluates the effectiveness of nanoemulsions (NE) containing two phthalocyanine photosensitizers; aluminum (III) phthalocyanine (AlPc) and zinc (II) phthalocyanine (ZnPc) in eliminating cancer cells. Human leukemic malignant (HL-60) and ovarian stromal cells (SCs) were treated with AlPc/ZnPc loaded NEs with or without diode laser irradiation. HL-60 leukemia cells in 2D culture were eliminated by treatment with 10 nM AlPc-NE or 0.1 µM ZnPc-NE, while no toxicity was observed in SCs. In 3D culture models, although the cells showed more resistance to the NEs as a result of limited oxygen and photosensitizer penetration, the treatment remained selective for cancer cells. These approaches have the potential to eliminate malignant cells from ovarian tissue fragments.

Combination of the Topical Photodynamic Therapy of Chloroaluminum Phthalocyanine Liposomes with Fexinidazole Oral Self-Emulsifying System as a New Strategy for Cutaneous Leishmaniasis Treatment.

Cutaneous leishmaniasis (CL) is a neglected tropical disease. The treatment is restricted to drugs, such as meglumine antimoniate and amphotericin B, that exhibit toxic effects, high cost, long-term treatment, and limited efficacy. The development of new alternative therapies, including the identification of effective drugs for the topical and oral treatment of CL, is of great interest. In this sense, a combination of topical photodynamic therapy (PDT) with chloroaluminum phthalocyanine liposomes (Lip-ClAlPc) and the oral administration of a self-emulsifying drug delivery system containing fexinidazole (SEDDS-FEX) emerges as a new strategy. The aim of the present study was to prepare, characterize, and evaluate the efficacy of combined therapy with Lip-ClAlPc and SEDDS-FEX in the experimental treatment of Leishmania (Leishmania) major. Lip-ClAlPc and SEDDS-FEX were prepared, and the antileishmanial efficacy study was conducted with the following groups: 1. Lip-ClAlPc (0.05 mL); 2. SEDDS-FEX (50 mg/kg/day); 3. Lip-ClAlPc (0.05 mL)+SEDDS-FEX (50 mg/kg/day) combination; 4. FEX suspension (50 mg/kg/day); and 5. control (untreated). BALB/c mice received 10 sessions of topical Lip-ClAlPc on alternate days and 20 consecutive days of SEDDS-FEX or FEX oral suspension. Therapeutical efficacy was evaluated via the parasite burden (limiting-dilution assay), lesion size (mm), healing of the lesion, and histological analyses. Lip-ClAlPc and SEDDS-FEX presented physicochemical characteristics that are compatible with the administration routes used in the treatments. Lip-ClAlPc+SEDDS-FEX led to a significant reduction in the parasitic burden in the lesion and spleen when compared to the control group (p < 0.05) and the complete healing of the lesion in 43% of animals. The Lip-ClAlPc+SEDDS-FEX combination may be promising for the treatment of CL caused by L. major.

Synthesis, Characterization, and Cytotoxicity Evaluation of Chlorambucil-Functionalized Mesoporous Silica Nanoparticles.

This study describes the synthesis and characterization of chlorambucil (CLB)-functionalized mesoporous silica nanoparticles (MSNs) for potential application in cancer therapy. The nanoparticles were designed with a diameter between 20 and 50 nm to optimize cellular uptake and avoid rapid clearance from the bloodstream. The synthesis method involved modifying a previously reported technique to reduce particle size. Successful functionalization with CLB was confirmed through various techniques, including Fourier transform infrared spectroscopy (FTIR) and elemental analysis. The cytotoxicity of the CLB-functionalized nanoparticles (MSN@NH2-CLB) was evaluated against human lung adenocarcinoma cells (A549) and colon carcinoma cells (CT26WT). The results suggest significantly higher cytotoxicity of MSN@NH2-CLB compared to unbound CLB, with improved selectivity towards cancer cells over normal cells. This suggests that MSN@NH2-CLB holds promise as a drug delivery system for targeted cancer therapy.

Combinatory Effect of Pequi Oil (Caryocar brasiliense)-Based Nanoemulsions Associated to Docetaxel and Anacardic Acid (Anacardium occidentale) in Triple-Negative Breast Cancer Cells In Vitro.

Combination therapy integrated with nanotechnology offers a promising alternative for breast cancer treatment. The inclusion of pequi oil, anacardic acid (AA), and docetaxel (DTX) in a nanoemulsion can amplify the antitumor effects of each molecule while reducing adverse effects. Therefore, the study aims to develop pequi oil-based nanoemulsions (PeNE) containing DTX (PDTX) or AA (PAA) and to evaluate their cytotoxicity against triple-negative breast cancer cells (4T1) in vitro. The PeNE without and with AA (PAA) and DTX (PDTX) were prepared by sonication and characterized by ZetaSizer® and electronic transmission microscopy. Viability testing and combination index (CI) were determined by MTT and Chou-Talalay methods, respectively. Flow cytometry was employed to investigate the effects of the formulations on cell structures. PeNE, PDTX, and PAA showed hydrodynamic diameter < 200 nm and a polydispersity index (PdI) of 0.3. The association PDTX + PAA induced a greater decrease in cell viability (~70%, p < 0.0001) and additive effect (CI < 1). In parallel, an association of the DTX + AA molecules led to antagonism (CI > 1). Additionally, PDTX + PAA induced an expressive morphological change, a major change in lysosome membrane permeation and mitochondria membrane permeation, cell cycle blockage in G2/M, and phosphatidylserine exposure. The study highlights the successful use of pequi oil nanoemulsions as delivery systems for DTX and AA, which enhances their antitumor effects against breast cancer cells. This nanotechnological approach shows significant potential for the treatment of triple-negative breast cancer.

Antitumor activity of photodynamic therapy performed with nanospheres containing zinc-phthalocyanine.

BACKGROUND: The 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. METHODS: Ehrlich 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. RESULTS: Intratumoral 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. CONCLUSIONS: PDT 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.