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1.
Pharmaceuticals (Basel) ; 16(12)2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38139786

RESUMO

Melanoma, a severe form of skin cancer intricately linked to genetic and environmental factors, is predicted to reach 100,000 new cases worldwide by 2040, underscoring the need for effective and safe treatment options. In this study, we assessed the efficacy of a photosensitizer called Chlorophyll A (Chl-A) incorporated into hydrogels (HGs) made of chitosan (CS) and poloxamer 407 (P407) for Photodynamic Therapy (PDT) against the murine melanoma cell line B16-F10. The HG was evaluated through various tests, including rheological studies, SEM, and ATR-FTIR, along with cell viability assays. The CS- and P407-based HGs effectively released Chl-A and possessed the necessary properties for topical application. The photodynamic activity of the HG containing Chl-A was evaluated in vitro, demonstrating high therapeutic potential, with an IC50 of 25.99 µM-an appealing result when compared to studies in the literature reporting an IC50 of 173.8 µM for cisplatin, used as a positive control drug. The developed formulation of CS and P407-based HG, serving as a thermosensitive system for topical applications, successfully controlled the release of Chl-A. In vitro cell studies associated with PDT exhibited potential against the melanoma cell line.

2.
3 Biotech ; 13(11): 357, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37818119

RESUMO

Breast cancer comprises approximately 20% of all malignant neoplasm cases globally. Due to the limitations associated with conventional therapeutic approaches, extensive investigations have been undertaken to develop novel treatments that exhibit enhanced specificity and minimized adverse effects. Consequently, the application of polymeric nanoformulations for targeted drug delivery has gained significant attention within the biomedical field. Therefore, the primary objective of this study was to explore the inherent advantages and efficacy of employing polymeric nanoformulations for drug delivery in breast cancer treatment, as compared to traditional therapies. A comprehensive literature search was conducted across prominent databases including PubMed/MEDLINE, Embase, and Scopus, utilizing specific search strings. This meticulous approach yielded a total of 12 relevant articles for in-depth analysis and discussion. The findings from the selected studies underscore the effectiveness of employing polymeric nanoparticles as a drug delivery strategy, showcasing noteworthy improvements in cellular uptake and sustained intracellular retention of encapsulated therapeutic agents. Additionally, these nanoformulations exhibited superior efficacy, safety, and drug delivery capabilities. The utilization of polymeric nanoparticles in drug delivery has demonstrated a substantial enhancement in treatment efficacy, with the ability to achieve higher concentrations of active ingredients within tumor tissues, augment cellular uptake and drug concentrations, and sustain intracellular retention. Consequently, this innovative approach prolongs drug release in lower quantities, ultimately contributing to improved treatment outcomes.

3.
Hum Reprod Open ; 2023(2): hoad005, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36895885

RESUMO

STUDY QUESTION: Is it possible to purge leukemia cells from ovarian tissue (OT) fragments before transplantation? SUMMARY ANSWER: Our photodynamic therapy (PDT) approach has been shown to efficiently destroy leukemia cells from tumor-infiltration mimicking models (TIMs), indicating the feasibility of this technique to purge OT samples. WHAT IS KNOWN ALREADY: Autotransplantation of cryopreserved OT is the most suitable option to preserve fertility for prepubertal girls and women who require immediate cancer treatment. Up until now, more than 200 live births have already been reported after OT cryopreservation and transplantation. Leukemia is the 12th most common cancer in Europe among prepubertal girls and women of reproductive age and in 2020, the estimated number of new leukemia cases was higher than 33 000 in girls between 0 and 19 years old. Unfortunately, once their health has been restored, autotransplantation of cryopreserved OT for leukemia patients is not advised due to the high risk of transferring malignant cells back to the patient leading to leukemia recurrence. STUDY DESIGN SIZE DURATION: To safely transplant the OT from leukemia patients and restore their fertility, our goal was to develop a PDT strategy to eliminate leukemia ex vivo. To this end, we designed OR141-loaded niosomes (ORN) to create the most effective formulation for ex vivo purging of acute myelogenous leukemia cells from OT fragments (n = 4). Moreover, to ensure that such treatments are not harmful to follicle survival and development so they can be deemed a potential fertility restoration alternative, the effect of the ORN-based PDT purging procedure on follicles was assessed after xenografting the photodynamic-treated OT in SCID mice (n = 5). The work was carried out between September 2020 and April 2022 at the Catholic University of Louvain. PARTICIPANTS/MATERIALS SETTING METHODS: After establishing the best ORN formulation, our PDT approach was used to eradicate HL60 cells from ex vivo TIMs prepared by microinjection of a cancer cell suspension into OT fragments. The purging efficiency was analyzed by droplet digital polymerase chain reaction and immunohistochemical analyses. Additionally, we evaluated the effect of ORN-based PDT on follicle density, survival and development, and tissue quality in terms of fibrotic areas and vascularization after 7-day xenotransplantation to immunodeficient mice. MAIN RESULTS AND THE ROLE OF CHANCE: The ex vivo purging of TIMs demonstrated that our PDT strategy could selectively eradicate the malignant cells from tissue fragments without affecting OT normal cells, as evidenced by PCR and immunohistochemical analysis. Regarding the effect of our PDT approach on follicle population and OT quality, our results after xenotransplantation revealed no significant difference between the follicle density of control (non-treated, grafted OT) and PDT-treated groups (2.38 ± 0.63 and 3.21 ± 1.94 morphologically normal follicles/mm2, respectively). In addition, our findings showed that the control and PDT-treated OT could be equally vascularized (7.65 ± 1.45% and 9.89 ± 2.21%, respectively). Similarly, the proportions of fibrotic area did not differ between the control (15.96 ± 5.94%) and PDT-treated groups (13.32 ± 3.05%). LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: This study did not use OT fragments from leukemia patients, but TIMs created after injection of HL60 cells into OT from healthy patients. Therefore, while the results are promising, whether our PDT approach will be equally successful in eliminating malignant cells from leukemia patients remains to be assessed. WIDER IMPLICATIONS OF THE FINDINGS: Our results showed that the purging procedure causes no significant impairment effect on follicle development and tissue quality, suggesting that our novel PDT procedure could be a promising strategy to destroy leukemia cells in fragments of OT, allowing safe transplantation in cancer survivors. STUDY FUNDING/COMPETING INTERESTS: This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (FNRS-PDR Convention grant number T.0004.20 awarded to C.A.A.); Fondation Louvain (awarded to C.A.A.; a Ph.D. scholarship awarded to S.M., as part of a legacy from Mr Frans Heyes, and a Ph.D. scholarship awarded to A.D. as part of a legacy from Mrs. Ilse Schirmer); and Foundation Against Cancer (grant number 2018-042 awarded to A.C.). The authors declare no competing interests.

4.
Pharmaceutics ; 14(11)2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36432650

RESUMO

Breast cancer is the most frequent cause of cancer death in women, representing the fifth leading cause of cancer death overall. Therefore, the growing search for the development of new treatments for breast cancer has been developed lately as well as drug delivery systems such as biocompatible metal-organic Frameworks (bio-MOFs). These may be promising and attractive for drug incorporation and release. The present study aims to develop a drug carrier system RCA (bioMOF-100 submitted to the activation process) containing incorporated curcumin (CCM), whose material surface is coated with folic acid molecules (FA) to promote the targeting of drug carrier systems to the tumor region. They were synthesized and characterized using several characterization techniques. The materials were submitted to drug encapsulation tests, whose encapsulation efficiency was 32.80% for CCM@RCA-1D. Using the 1H nuclear magnetic resonance (NMR) spectroscopy technique, it was possible to verify the appearance of signals referring to folic acid, suggesting success in the functionalization of these matrices. In vitro tests such as cell viability and type of cell death were evaluated in both series of compounds (CCM@RCA-1D, CCM@RCA-1D/FA) in breast tumor lines. The results revealed low toxicity of the materials and cell death by late apoptosis. Thus, these results indicate that the matrices studied can be promising carriers in the treatment of breast cancer.

5.
Photodiagnosis Photodyn Ther ; 40: 103139, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36198387

RESUMO

In 2020, the estimated number of new leukemia cases was higher than 30,000 in girls between 0 and 19 years old. Due to cancer treatment, some of these patients may lose both endocrine and reproductive functions. Transplantation of cryopreserved ovarian tissue is not advised after cancer remission because it has a high risk of reintroducing malignant cells in the patient, potentially leading to leukemia recurrence. To safely transplant the ovarian tissue from these patients and restore their fertility, our goal was to develop a photodynamic therapy (PDT) strategy to eliminate leukemia ex vivo. To this end, we designed, optimized, and characterized OR141-loaded niosomes (ORN) to develop the most effective formulation for ex vivo purging ovarian fragments from chronic myelogenous leukemia cells. After establishing the best ORN formulation, the PDT efficiency of optimized ORN was determined for human ovarian stromal cells and acute myeloid leukemia cell line (HL60). Blank niosomes treatment on ovarian stromal cells causes no significant toxicity, showing that the composition of the nanoparticle is not toxic. On the other hand, the in vitro studies showed that while ovarian stromal cells were still viable (82.04 ± 2.79%) after the treatment by 0.5 µM ORN, the same treatment yielded 95.43 ± 3.89% toxicity and cell death in the cancer cells. In conclusion, our results showed that our novel PDT procedure could be a promising strategy to destroy leukemia cells in ovarian tissue fragments allowing safe transplantation in cancer survivors.


Assuntos
Preservação da Fertilidade , Leucemia Mieloide Aguda , Fotoquimioterapia , Feminino , Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Preservação da Fertilidade/métodos , Fotoquimioterapia/métodos , Criopreservação , Ovário/patologia
6.
J Control Release ; 351: 164-173, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36165834

RESUMO

Nanoemulsion, or nanoscaled-size emulsions, is a thermodynamically stable system formed by blending two immiscible liquids, blended with an emulsifying agent to produce a single phase. Nanoemulsion science has advanced rapidly in recent years, and it has opened up new opportunities in a variety of fields, including pharmaceuticals, biotechnology, food, and cosmetics. Nanoemulsion has been recognized as a potential drug delivery technology for various drugs, such as photosensitizing agents (PS). In photodynamic therapy (PDT), PSs produce cytotoxic reactive oxygen species under specific light irradiation, which oxidize the surrounding tissues. Over the past decades, the idea of PS-loaded nanoemulsions has received researchers' attention due to their ability to overcome several limitations of common PSs, such as limited permeability, non-specific phototoxicity, hydrophobicity, low bioavailability, and self-aggregation tendency. This review aims to provide fundamental knowledge of nanoemulsion formulations and the principles of PDT. It also discusses nanoemulsion-based PDT strategies and examines nanoemulsion advantages for PDT, highlighting future possibilities for nanoemulsion use.


Assuntos
Antineoplásicos , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Emulsões , Antineoplásicos/uso terapêutico
7.
J Photochem Photobiol B ; 234: 112546, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36029759

RESUMO

The field of photodynamic therapy (PDT) for treating various malignant neoplasms has been given researchers' attention due to its ability to be a selective and minimally invasive cancer therapy strategy. The possibility of tumor cell infection and hence high recurrence rates in cancer patients tends to restrict autologous transplantation. So, the photodynamic tissue purging process, which consists of selective photoinactivation of the malignant cells in the graft, is defined as a compromising strategy to purify contaminated tissues before transplantation. In this strategy, the direct malignant cells' death results from the reactive oxygen species (ROS) generation through the activation of a photosensitizer (PS) by light exposure in the presence of oxygen. Since new PS generations can effectively penetrate the tissue, PDT could be an ideal ex vivo tissue purging protocol that eradicates cancer cells derived from various malignancies. The challenge is that the applied pharmacologic ex vivo tissue purging should efficiently induce tumor cells with minor influence on normal tissue cells. This review aims to provide an overview of the current status of the most effective PDT strategies and PS development concerning their potential application in ex vivo purging before hematopoietic stem cell or ovarian tissue transplantation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neoplasias , Fotoquimioterapia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Transplante Autólogo/métodos
8.
Nanomaterials (Basel) ; 12(10)2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35630905

RESUMO

Diets rich in omega-3 or -6 fatty acids will produce different profiles for cell membranes phospholipid constitutions. Omegas 3 and 6 are part of the diet and can modulate the inflammatory profile. We evaluated the effects of the oral absorption of fish oil, when associated with a lipid nanoemulsion in an experimental pulmonary inflammatory model. Pulmonary fibrosis is a disease associated with excessive extracellular matrix deposition. We determined to investigate the morphophysiological mechanisms in mice that were pretreated after induction with bleomycin (BLM). The pretreatment was for 21 days with saline solution, sunflower oil (SO), fish oil (FO), and fish oil nanoemulsion (NEW3). The animals received a daily dose of 50 mg/Kg of docosahexaenoic acid DHA and 10 mg/Kg eicosapentaenoic (EPA) (100 mg/Kg), represented by a daily dose of 40 µL of NEW3. The blank group was treated with the same amount daily (40 µL) during the 21 days of pretreatment. The animals were treated with SO and FO, 100 mg/Kg (containing 58 mg/Kg of polyunsaturated fats/higher% linoleic acid) and 100 mg/Kg (50 mg/Kg of DHA and 10 mg/Kg EPA), respectively. A single dose of 5 mg/mL (50 µL) bleomycin sulfate, by the intratracheal surgical method in BALB/cAnNTac (BALB/c). NEW3 significantly reduced fibrotic progression, which can be evidenced by the protection from loss of body mass, increase in respiratory incursions per minute, decreased spacing of alveolar septa, decreased severity of fibrosis, and changes in the respiratory system. NEW3 attenuated the inflammatory changes developed in the experimental model of pulmonary fibrosis, while group SO showed a significant increase in inflammatory changes. This concluded that the presented results demonstrated that is possible to positively modulate the immune and inflamamtory response to an external agressor, by changing the nutitional intake of specific fatty acids, such as omega-3 placed in fish oil. Moreover, these benefits can be improved by the nanoencapsulation of fish oil in lipid nanoemulsions.

9.
Pharmaceutics ; 14(1)2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35057091

RESUMO

Photodynamic therapy (PDT) has been clinically employed to treat mainly superficial cancer, such as basal cell carcinoma. This approach can eliminate tumors by direct cytotoxicity, tumor ischemia, or by triggering an immune response against tumor cells. Among the immune-related mechanisms of PDT, the induction of immunogenic cell death (ICD) in target cells is to be cited. ICD is an apoptosis modality distinguished by the emission of damage-associated molecular patterns (DAMP). Therefore, this study aimed to analyze the immunogenicity of CT26 and 4T1 treated with PDT mediated by aluminum-phthalocyanine in nanoemulsion (PDT-AlPc-NE). Different PDT-AlPc-NE protocols with varying doses of energy and AlPc concentrations were tested. The death mechanism and the emission of DAMPs-CRT, HSP70, HSP90, HMGB1, and IL-1ß-were analyzed in cells treated in vitro with PDT. Then, the immunogenicity of these cells was assessed in an in vivo vaccination-challenge model with BALB/c mice. CT26 and 4T1 cells treated in vitro with PDT mediated by AlPc IC50 and a light dose of 25 J/cm2 exhibited the hallmarks of ICD, i.e., these cells died by apoptosis and exposed DAMPs. Mice injected with these IC50 PDT-treated cells showed, in comparison to the control, increased resistance to the development of tumors in a subsequent challenge with viable cells. Mice injected with 4T1 and CT26 cells treated with higher or lower concentrations of photosensitizer and light doses exhibited a significantly lower resistance to tumor development than those injected with IC50 PDT-treated cells. The results presented in this study suggest that both the photosensitizer concentration and light dose affect the immunogenicity of the PDT-treated cells. This event can affect the therapy outcomes in vivo.

10.
Nanotechnology ; 33(20)2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35100566

RESUMO

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.


Assuntos
Neoplasias da Mama/terapia , Hipertermia Induzida , Nanopartículas de Magnetita/uso terapêutico , Nanocápsulas/uso terapêutico , Compostos de Selênio/uso terapêutico , Animais , Neoplasias da Mama/patologia , Carcinoma de Ehrlich/patologia , Carcinoma de Ehrlich/terapia , Ciclo Celular/efeitos dos fármacos , Terapia Combinada , Fragmentação do DNA/efeitos dos fármacos , Feminino , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Nanocápsulas/química , Nanocápsulas/ultraestrutura , Compostos de Selênio/química , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos
11.
Nanomedicine (Lond) ; 17(3): 167-179, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35048742

RESUMO

Aim: To develop a new curcumin carrier consisting of murumuru butter nanoparticles (SLN-Cs). Methods: A phase-inversion temperature method was used to produce SLN-Cs. The interaction of SLN-Cs with murine colon adenocarcinoma (CT26) cells in vitro was analyzed by confocal microscopy. Results: Stable SLN-Cs with a high curcumin-loading capacity were obtained. The SLN-Cs were more toxic to CT26 than free curcumin. Fluorescence microscopy images showed the SLN-Cs to be taken up by CT26 cells in vitro. Conclusion: These results indicate that SLN-Cs are suitable carriers of curcumin in aqueous media.


Assuntos
Curcumina , Nanopartículas , Animais , Portadores de Fármacos , Lipídeos , Lipossomos , Camundongos , Nanopartículas/toxicidade , Tamanho da Partícula
12.
Nanomedicine (Lond) ; 17(27): 2073-2088, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36853205

RESUMO

Aim: Investigate the heterogeneous tumor tissue organization and examine how this condition can interfere with the passive delivery of a lipid nanoemulsion in two breast cancer preclinical models (4T1 and Ehrlich). Materials & methods: The authors used in vivo image techniques to follow the nanoemulsion biodistribution and microtomography, as well as traditional histopathology and electron microscopy to evaluate the tumor structural characteristics. Results & conclusion: Lipid nanoemulsion was delivered to the tumor, vascular organization depends upon the subtumoral localization and this heterogeneous organization promotes a nanoemulsion biodistribution to the highly vascular peripherical region. Also, the results are presented with a comprehensive mathematical model, describing the differential biodistribution in two different breast cancer models, the 4T1 and Ehrlich models.


Assuntos
Neoplasias da Mama , Nanopartículas , Humanos , Feminino , Linhagem Celular Tumoral , Distribuição Tecidual , Nanopartículas/química , Lipídeos , Neoplasias da Mama/diagnóstico por imagem , Emulsões/química
14.
Photodiagnosis Photodyn Ther ; 36: 102555, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34597832

RESUMO

Due to the risk of reintroducing malignant cells, autotransplantation of cryopreserved ovarian tissue is not allowed in leukemia patients. In order to restore fertility in these patients, ex vivo purging of ovarian fragments could be proposed as a strategy to eradicate malignant cells before grafting. Photodynamic therapy (PDT), as a clinical-approved modality, is a minimally invasive and selective therapeutic for eliminating malignant cells. The present work aims therefore to evaluate the phototoxicity of two photosensitizers (aluminum phthalocyanine (AlPc) and zinc phthalocyanine (ZnPc)) on leukemia cells. To this end, two lines of malignant cells (K562 and HL-60) and isolated ovarian stromal cells (control) were treated by PDT using a diode laser with various energy densities. Cell viability after the treatment, the amount of generated reactive oxygen species, dark toxicity of the photosensitizers, and single-cell morphology were studied. Our results demonstrated that using irradiation with the energy density of 10 J/cm2, 1 µM AlPc could significantly reduce the viability of K562 (4.73 ± 0.14%) and HL-60 (2.74 ± 0.31%). Similarly, the viability of these cells was reduced (K562 cells: 3.84 ± 0.81%; HL-60 cells: 6.82 ± 3.21%) with 1 µM ZnPc and an energy density of 50 J/cm2. On the other hand, these PDT protocols had no significant effect on stromal cells. These findings indicate that our approach can be a promising strategy for the safe restoration of fertility in leukemia patients. However, further studies are necessary to assess its efficiency in ovarian fragments containing malignant cells to determine their eradication rate and the effect of our treatment on the survival of stromal cells and preantral follicles.


Assuntos
Compostos Organometálicos , Fotoquimioterapia , Linhagem Celular Tumoral , Humanos , Indóis , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Zinco
15.
J Control Release ; 339: 75-90, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34562540

RESUMO

The multidisciplinary field of photodynamic therapy (PDT) is a combination of photochemistry and photophysics sciences, which has shown tremendous potential for cancer therapy application. PDT employs a photosensitizing agent (PS) and light to form cytotoxic reactive oxygen species and subsequently oxidize light-exposed tissue. Despite numerous advantages of PDT and enormous progress in this field, common PSs are still far from ideal treatment because of their poor permeability, non-specific phototoxicity, side effects, hydrophobicity, weak bioavailability, and tendency to self-aggregation. To circumvent these limitations, PS can be encapsulated in liposomes, an advanced drug delivery system that has demonstrated the ability to enhance drug permeability into biological membranes and loading both hydrophobic and lipophilic agents. Moreover, liposomes can also be coated by targeting agents to improve delivery efficiency. The present review aims to summarize the principles of PDT, various PS generations, PS-loaded nanoparticles, liposomes, and their impact on PDT, then discuss recent photodynamic cancer therapy strategies using liposomes as PS-loaded vectors, and highlight future possibilities and perspectives.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Lipossomos/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico
16.
Biomed Pharmacother ; 142: 112000, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34426249

RESUMO

The main goal of this study is to evaluate the efficacy of the paclitaxel (PTX) drug formulated with a liposomal nanosystem (L-PTX) in a peritoneal carcinomatosis derived from ovarian cancer. In vitro cell viability studies with the human ovarian cancer line A2780 showed a 50% decrease in the inhibitory concentration for L-PTX compared to free PTX. A2780 cells treated with the L-PTX formulation demonstrated a reduced capacity to form colonies in comparison to those treated with PTX. Cell death following L-PTX administration hinted at apoptosis, with most cells undergoing initial apoptosis. A2780 cells exhibited an inhibitory migration profile when analyzed by Wound Healing and real-time cell analysis (xCELLigence) methods after L-PTX administration. This inhibition was related to decreased expression of the zinc finger E-box-binding homeobox 1 (ZEB1) and transforming growth factor 2 (TGF-ß2) genes. In vivoL-PTX administration strongly inhibited tumor cell proliferation in ovarian peritoneal carcinomatosis derived from ovarian cancer, indicating higher antitumor activity than PTX. L-PTX formulation did not show toxicity in the mice model. This study demonstrated that liposomal paclitaxel formulations are less toxic to normal tissues than free paclitaxel and are more effective in inhibiting tumor cell proliferation/migration and inducing ZEB1/TGF-ß2 gene expression.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/farmacologia , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Apoptose/efeitos dos fármacos , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Lipossomos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Neoplasias Peritoneais/tratamento farmacológico
17.
Biomed Pharmacother ; 138: 111505, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33773467

RESUMO

Doxorubicin (DOX) is an anthracycline antibiotic used in the fight against many types of cancer. Although it is quite effective for this purpose, its clinical use is limited by its severe side effects, highlighting the relevance of efforts to identify substances that act to minimize these effects. In this work, we sought to verify the ability of andiroba oil (AO) and a nanoemulsion of andiroba oil (AN) to lessen the side effects of DOX. The animals were separated into 7 groups with 6 animals each: mice treated with AO (2000 mg/kg), AN (2000 mg/kg), the antineoplastic agent DOX (40 mg/kg), AO+DOX, AN+DOX and solvent controls was used of negative control (corn oil and nanoemulsion surfactant). AO and AN were administered for 14 consecutive days orally by gavage and on the 13th day, applied DOX by intraperitoneal route (i.p.), in order to evaluate the protective potential of andiroba. The animals were euthanized on the 15th day. Hematological, biochemical, histological, and immunohistochemical parameters were analyzed. Andiroba reduced several aspects of the severity of lesions caused by DOX, decreasing hematotoxicity and the severity of histological changes in the liver and kidneys, and reducing the frequency of apoptotic cell death. In many cases, AN showed greater efficacy than AO alone, reflecting the feasibility of using this nanotechnology to improve the pharmacokinetics of lipid compounds in the body. The study sheds new light on the therapeutic benefits of andiroba and suggests new ways for investigating how the quantity and quality of lipid compounds affect exposed organisms.


Assuntos
Antineoplásicos/toxicidade , Doxorrubicina/toxicidade , Emulsões/uso terapêutico , Meliaceae , Óleos de Plantas/uso terapêutico , Animais , Emulsões/isolamento & purificação , Emulsões/farmacologia , Feminino , Injeções Intraperitoneais , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Camundongos , Óleos de Plantas/isolamento & purificação , Óleos de Plantas/farmacologia , Baço/efeitos dos fármacos , Baço/patologia
18.
RSC Adv ; 11(11): 6346-6352, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35423156

RESUMO

Bioactive carbon dots (C-dots) with ca. 4 nm were successfully produced with singular photophysical properties, low-toxicity and interesting immunological response. The optical properties of the C-dots were investigated and the "light-up" behaviour enabled them to be explored in glucose detection and bioimaging experiments (mitochondrial selective probe). C-dots were not selective to the tumour region and several fluorescent spots were visualized spread on animal bodies. The histology investigations showed that cancer-bearing mice treated with C-dots presented a large number of regions with necrosis and inflammatory infiltrates, which were not identified for cancer-bearing mice without the treatment. These results suggested that C-dots have the potential to be explored as an immune therapy agent for melanoma skin cancer.

19.
Braz. arch. biol. technol ; 64: e21190387, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1153290

RESUMO

HIGHLIGHTS Production of lipid nanoemulsions (<100 nm) of industrial interest with low energy demand. The antioxidant properties of babassu oil have been improved and the nanoemulsions are not cytotoxic. Babassu oil is a food and medicinal product. The nanoemulsion is strategic for the developed of new antioxidants phytotherapeutics.


Abstract Background: Babassu oil is an extract from a Brazilian native coconut (Orbignya phalerata Martius) and is used both as a food and a medicinal product. Methods: we produced two babassu oil nanoemulsions and evaluated them regarding their nanoscopic stability, antioxidant activity and cytotoxicity.The nanoemulsions were characterized by Dynamic Light Scattering, and their stability was investigated for 120 days. The antioxidant activity was assessed by Spectroscopy Electron Paramagnetic Resonance, and the cytotoxicity was assessed by a colorimetric method (MTT) with the NIH/3T3 cell lineage. Results: the results showed nanoemulsions with average hydrodynamic diameter lower than 100 nm (p(0.001).and a polydispersity index of less than 0.3 (p(0.001), indicating monodisperse systems and good stability at room temperature. The exposure of nanoemulsions at varying pH revealed that the isoelectric point was at 3.0, and the images obtained by Transmission Electron Microscopy showed spherical droplets with a size 27 nm. The antioxidant activity showed that the babassu nanoemulsions exposed to free radicals had a better response when compared to the oil free samples. The cell viability assays showed low toxicity of the formulation with viability over 92% (p(0.05). Conclusion: babassu oil nanoformulations showed low polydispersity and kinetic stability with effective antioxidant action. Therefore, they can be promising for application in the food industry or as antioxidant phytotherapeutics.


Assuntos
Óleo de Palmeira/química , Nanotecnologia , Antioxidantes , Extratos Vegetais/química , Indústria Alimentícia , Citotoxinas , Microscopia Eletrônica de Transmissão , Emulsões , Nanocompostos
20.
Nanomedicine (Lond) ; 15(28): 2753-2770, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33179587

RESUMO

Aim: To investigate the effect of liposomes containing the classical cytotoxic drugs paclitaxel and doxorubicin (Lipo-Pacli/Dox), against a metastatic breast cancer model. We also investigated if Lipo-Pacli/Dox was capable of reverting the tolerogenic environment of metastatic lesions. Materials & methods: Immunogenic cell death induction by the Pacli/Dox combination was assessed in vitro. Antitumor activity and in vivo safety of Lipo-Pacli/Dox were evaluated using a 4T1 breast cancer mouse model Results: Lipo-Pacli/Dox, with a size of 189 nm and zeta potential of -5.01 mV, promoted immune system activation and partially controlled the progression of pulmonary metastasis. Conclusion: Lipo-Pacli/Dox was useful to control both primary tumor and lung metastasis in breast cancer (4T1) mice model. Additionally, Lipo-Pacli/Dox acts as an immunological modulator for this metastatic breast cancer model.


Assuntos
Lipossomos , Neoplasias Pulmonares , Animais , Antibióticos Antineoplásicos , Linhagem Celular Tumoral , Doxorrubicina , Neoplasias Pulmonares/tratamento farmacológico , Linfócitos , Camundongos , Camundongos Endogâmicos BALB C , Paclitaxel , Prognóstico
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