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1.
Drug Discov Today ; : 103981, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38614161

RESUMO

The combination of peptides and nanoparticles in cancer therapy has shown synergistic results. Nanoparticle functionalization with peptides can increase their targeting ability towards tumor cells. In some cases, the peptides can develop self-assembled nanoparticles, in combination with drugs, for targeted cancer therapy. The peptides can be loaded into nanoparticles and can be delivered by other drugs for synergistic cancer removal. Multifunctional types of peptide-based nanoparticles, including pH- and redox-sensitive classes, have been introduced in cancer therapy. The tumor microenvironment remolds, and the acceleration of immunotherapy and vaccines can be provided by peptide nanoparticles. Moreover, the bioimaging and labeling of cancers can be mediated by peptide nanoparticles. Therefore, peptides can functionalize nanoparticles in targeted cancer therapy.

2.
Cancer Lett ; 591: 216857, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38583648

RESUMO

The considerable death rates and lack of symptoms in early stages of gastric cancer (GC) make it a major health problem worldwide. One of the most prominent risk factors is infection with Helicobacter pylori. Many biological processes, including those linked with cell death, are disrupted in GC. The cellular "self-digestion" mechanism necessary for regular balance maintenance, autophagy, is at the center of this disturbance. Misregulation of autophagy, however, plays a role in the development of GC. In this review, we will examine how autophagy interacts with other cell death processes, such as apoptosis and ferroptosis, and how it affects the progression of GC. In addition to wonderful its role in the epithelial-mesenchymal transition, it is engaged in GC metastasis. The role of autophagy in GC in promoting drug resistance stands out. There is growing interest in modulating autophagy for GC treatment, with research focusing on natural compounds, small-molecule inhibitors, and nanoparticles. These approaches could lead to breakthroughs in GC therapy, offering new hope in the fight against this challenging disease.

3.
Cancer Lett ; : 216867, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38593919

RESUMO

Autophagy, a self-digestion mechanism, has emerged as a promising target in the realm of cancer therapy, particularly in bladder cancer (BCa), a urological malignancy characterized by dysregulated biological processes contributing to its progression. This highly conserved catabolic mechanism exhibits aberrant activation in pathological events, prominently featured in human cancers. The nuanced role of autophagy in cancer has been unveiled as a double-edged sword, capable of functioning as both a pro-survival and pro-death mechanism in a context-dependent manner. In BCa, dysregulation of autophagy intertwines with cell death mechanisms, wherein pro-survival autophagy impedes apoptosis and ferroptosis, while pro-death autophagy diminishes tumor cell survival. The impact of autophagy on BCa progression is multifaceted, influencing metastasis rates and engaging with the epithelial-mesenchymal transition (EMT) mechanism. Pharmacological modulation of autophagy emerges as a viable strategy to impede BCa progression and augment cell death. Notably, the introduction of nanoparticles for targeted autophagy regulation holds promise as an innovative approach in BCa suppression. This review underscores the intricate interplay of autophagy with cell death pathways and its therapeutic implications in the nuanced landscape of bladder cancer.

4.
Cancer Lett ; : 216860, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38583650

RESUMO

Cancer is the result of genetic abnormalities that cause normal cells to grow into neoplastic cells. Cancer is characterized by several distinct features, such as uncontrolled cell growth, extensive spreading to other parts of the body, and the ability to resist treatment. The scientists have stressed the development of nanostructures as novel therapeutic options in suppressing cancer, in response to the emergence of resistance to standard medicines. One of the specific mechanisms with dysregulation during cancer is autophagy. Nanomaterials have the ability to specifically carry medications and genes, and they can also enhance the responsiveness of tumor cells to standard therapy while promoting drug sensitivity. The primary mechanism in this process relies on autophagosomes and their fusion with lysosomes to break down the components of the cytoplasm. While autophagy was initially described as a form of cellular demise, it has been demonstrated to play a crucial role in controlling metastasis, proliferation, and treatment resistance in human malignancies. The pharmacokinetic profile of autophagy modulators is poor, despite their development for use in cancer therapy. Consequently, nanoparticles have been developed for the purpose of delivering medications and autophagy modulators selectively and specifically to the cancer process. Furthermore, several categories of nanoparticles have demonstrated the ability to regulate autophagy, which plays a crucial role in defining the biological characteristics and response to therapy of tumor cells.

5.
J Nutr Biochem ; : 109647, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38604457

RESUMO

Macrophages are phagocytic cells with important physiological functions, including the digestion of cellular debris, foreign substances, and microbes, as well as tissue development and homeostasis. The tumor microenvironment (TME) shapes the aggressiveness of cancer, and the biological and cellular interactions in this complicated space can determine carcinogenesis. The TME can determine the progression, biological behavior, and therapy resistance of human cancers. The macrophages are among the most abundant cells in the TME, and their functions and secretions can determine tumor progression. The education of macrophages to M2 polarization can accelerate cancer progression, and therefore, the re-education and reprogramming of these cells is promising. Moreover, macrophages can cause inflammation in aggravating pathological events, including cardiovascular diseases, diabetes, and neurological disorders. The natural products are pleiotropic and broad-spectrum functional compounds that have been deployed as ideal alternatives to conventional drugs in the treatment of cancer. The biological and cellular interactions in the TME can be regulated by natural products, and for this purpose, they enhance the M1 polarization of macrophages, and in addition to inhibiting proliferation and invasion, they impair the chemoresistance. Moreover, since macrophages and changes in the molecular pathways in these cells can cause inflammation, the natural products impair the pro-inflammatory function of macrophages to prevent the pathogenesis and progression of diseases. Even a reduction in macrophage-mediated inflammation can prevent organ fibrosis. Therefore, natural product-mediated macrophage targeting can alleviate both cancerous and non-cancerous diseases.

6.
ACS Appl Mater Interfaces ; 16(13): 15718-15729, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38506616

RESUMO

Surgical removal of tumor tissue remains the primary clinical approach for addressing breast cancer; however, complete tumor excision is challenging, and the remaining tumor cells can lead to tumor recurrence and metastasis over time, which substantially deteriorates the life quality of the patients. With the aim to improve local cancer radiotherapy, this work reports the fabrication of alginate (Alg) scaffolds containing bovine serum albumin (BSA)-coated bismuth sulfide (Bi2S3@BSA) nanoradiosensitizers using three-dimensional (3D) printing. Under single-dose X-ray irradiation in vitro, Alg-Bi2S3@BSA scaffolds significantly increase the formation of reactive oxygen species, enhance the inhibition of breast cancer cells, and suppress their colony formation capacity. In addition, scaffolds implanted under tumor tissue in murine model show high therapeutic efficacy by reducing the tumor volume growth rate under single-dose X-ray irradiation, while histological observation of main organs reveals no cytotoxicity or side effects. 3D-printed Alg-Bi2S3@BSA scaffolds produced with biocompatible and biodegradable materials may potentially lower the recurrence and metastasis rates in breast cancer patients by inhibiting residual tumor cells following postsurgery as well as exhibit anticancer properties in other solid tumors.


Assuntos
Bismuto , Neoplasias da Mama , Nanopartículas , Sulfetos , Humanos , Animais , Camundongos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Alginatos , Tecidos Suporte , Impressão Tridimensional , Engenharia Tecidual
7.
Biomed Pharmacother ; 173: 116465, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38507955

RESUMO

This study introduces an innovative co-delivery approach using the MCM-co-polymerized nanosystem, integrating chitosan and polyethylene glycol, and targeted by the MUC-1 aptamer (MCM@CS@PEG-APT). This system enables simultaneous delivery of the GFP plasmid and doxorubicin (DOX). The synthesis of the nanosystem was thoroughly characterized at each step, including FTIR, XRD, BET, DLS, FE-SEM, and HRTEM analyses. The impact of individual polymers (chitosan and PEG) on payload retardation was compared to the co-polymerized MCM@CS@PEG conjugation. Furthermore, the DOX release mechanism was investigated using various kinetic models. The nanosystem's potential for delivering GFP plasmid and DOX separately and simultaneously was assessed through fluorescence microscopy and flow cytometry. The co-polymerized nanosystem exhibited superior payload entrapment (1:100 ratio of Plasmid:NPs) compared to separately polymer-coated counterparts (1:640 ratio of Plasmid:NPs). Besides, the presence of pH-sensitive chitosan creates a smart nanosystem for efficient DOX and GFP plasmid delivery into tumor cells, along with a Higuchi model pattern for drug release. Toxicity assessments against breast tumor cells also indicated reduced off-target effects compared to pure DOX, introducing it as a promising candidate for targeted cancer therapy. Cellular uptake findings demonstrated the nanosystem's ability to deliver GFP plasmid and DOX separately into MCF-7 cells, with rates of 32% and 98%, respectively. Flow cytometry results confirmed efficient co-delivery, with 42.7% of cells showing the presence of both GFP-plasmid and DOX, while 52.2% exclusively contained DOX. Overall, our study explores the co-delivery potential of the MCM@CS@PEG-APT nanosystem in breast cancer therapy. This system's ability to co-deliver multiple agents preciselyopens new avenues for targeted therapeutic strategies.


Assuntos
Neoplasias da Mama , Quitosana , Nanopartículas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Polimerização , Doxorrubicina/farmacologia , Oligonucleotídeos , Plasmídeos , DNA , Sistemas de Liberação de Medicamentos/métodos , Portadores de Fármacos
8.
Small ; : e2308479, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385813

RESUMO

Microneedles (MNs) have maintained their popularity in therapeutic and diagnostic medical applications throughout the past decade. MNs are originally designed to gently puncture the stratum corneum layer of the skin and have lately evolved into intelligent devices with functions including bodily fluid extraction, biosensing, and drug administration. MNs offer limited invasiveness, ease of application, and minimal discomfort. Initially manufactured solely from metals, MNs are now available in polymer-based varieties. MNs can be used to create systems that deliver drugs and chemicals uniformly, collect bodily fluids, and are stimulus-sensitive. Although these advancements are favorable in terms of biocompatibility and production costs, they are insufficient for the therapeutic use of MNs. This is the first comprehensive review that discusses individual MN functions toward the evolution and development of smart and multifunctional MNs for a variety of novel and impactful future applications. The study examines fabrication techniques, application purposes, and experimental details of MN constructs that perform multiple functions concurrently, including sensing, drug-molecule release, sampling, and remote communication capabilities. It is highly likely that in the near future, MN-based smart devices will be a useful and important component of standard medical practice for different applications.

9.
Cancer Metastasis Rev ; 43(1): 457-479, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38227149

RESUMO

Epithelial-mesenchymal transition (EMT) is a complicated molecular process that governs cellular shape and function changes throughout tissue development and embryogenesis. In addition, EMT contributes to the development and spread of tumors. Expanding and degrading the surrounding microenvironment, cells undergoing EMT move away from the main location. On the basis of the expression of fibroblast-specific protein-1 (FSP1), fibroblast growth factor (FGF), collagen, and smooth muscle actin (-SMA), the mesenchymal phenotype exhibited in fibroblasts is crucial for promoting EMT. While EMT is not entirely reliant on its regulators like ZEB1/2, Twist, and Snail proteins, investigation of upstream signaling (like EGF, TGF-ß, Wnt) is required to get a more thorough understanding of tumor EMT. Throughout numerous cancers, connections between tumor epithelial and fibroblast cells that influence tumor growth have been found. The significance of cellular crosstalk stems from the fact that these events affect therapeutic response and disease prognosis. This study examines how classical EMT signals emanating from various cancer cells interfere to tumor metastasis, treatment resistance, and tumor recurrence.


Assuntos
Transição Epitelial-Mesenquimal , Neoplasias , Humanos , Transição Epitelial-Mesenquimal/fisiologia , Neoplasias/metabolismo , Transdução de Sinais , Fenótipo , Resistência a Medicamentos , Linhagem Celular Tumoral , Microambiente Tumoral
10.
Transl Oncol ; 39: 101838, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38016356

RESUMO

As a clinically approved treatment strategy, chemotherapy-mediated tumor suppression has been compromised, and in spite of introducing various kinds of anticancer drugs, cancer eradication with chemotherapy is still impossible. Chemotherapy drugs have been beneficial in improving the prognosis of cancer patients, but after resistance emerged, their potential disappeared. Oxaliplatin (OXA) efficacy in tumor suppression has been compromised by resistance. Due to the dysregulation of pathways and mechanisms in OXA resistance, it is suggested to develop novel strategies for overcoming drug resistance. The targeted delivery of OXA by nanostructures is described here. The targeted delivery of OXA in cancer can be mediated by polymeric, metal, lipid and carbon nanostructures. The advantageous of these nanocarriers is that they enhance the accumulation of OXA in tumor and promote its cytotoxicity. Moreover, (nano)platforms mediate the co-delivery of OXA with drugs and genes in synergistic cancer therapy, overcoming OXA resistance and improving insights in cancer patient treatment in the future. Moreover, smart nanostructures, including pH-, redox-, light-, and thermo-sensitive nanostructures, have been designed for OXA delivery and cancer therapy. The application of nanoparticle-mediated phototherapy can increase OXA's potential in cancer suppression. All of these subjects and their clinical implications are discussed in the current review.

11.
Sci Rep ; 13(1): 15131, 2023 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-37704633

RESUMO

To solve the traditional radiotherapy obstacles, and also to enhance the radiation therapy efficacy various radiosensitizers have been developed. Radiosensitizers are promising agents that under X-ray irradiation enhance injury to tumor tissue by accelerating DNA damage. In this report, silver-silver sulfide nanoparticles (Ag-Ag2S NPs) were synthesized via a facile, one-pot and environmentally friendly biomineralization method. Ag-Ag2S was coated with bovine serum albumin (BSA) in situ and applied as an X-ray sensitizer to enhance the efficiency of radiotherapy. Also, folic acid (FA) was conjugated to Ag-Ag2S@BSA to impart active targeting capability to the final formulation (Ag-Ag2S@BSA-FA). Prepared NPs were characterized by transmission electron microscopes (TEM), scanning electron microscope (SEM), dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-Vis), X-ray diffraction analysis (XRD), and X-ray photoelectron spectroscopy (XPS) techniques. Results show that most of the NPs have well-defined uniform Janus structures. The biocompatibility of the NPs was then evaluated both in vitro and in vivo. A series of in vitro assays were performed on 4T1 cancer cells to evaluate the therapeutic efficacy of the designed NPs. In addition, the radio-enhancing ability of the NPs was tested on the 4T1 breast cancer murine model. MTT, live and dead cell staining, apoptosis, ROS generation, and clonogenic in vitro assays demonstrated the efficacy of NPs as radiosensitizers in radiotherapy. In vivo results as well as H&E staining tumor tissues confirmed tumor destruction in the group that received Ag-Ag2S@BSA-FA NPs and exposed to X-ray. The results showed that prepared tumor-targeted Ag-Ag2S@BSA-FA NPs could be potential candidates as radiosensitizers for enhanced radiotherapy.


Assuntos
Neoplasias , Radioterapia (Especialidade) , Radiossensibilizantes , Animais , Camundongos , Prata/farmacologia , Biomineralização , Radiossensibilizantes/farmacologia , Projetos de Pesquisa , Ácido Fólico
12.
ACS Appl Bio Mater ; 6(6): 2266-2276, 2023 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-37273221

RESUMO

Fruits are safe, toxin-free, and biomolecule-rich raw materials that may be utilized to decrease metal ions and stabilize nanoparticles. Here, we demonstrate the green synthesis of magnetite nanoparticles which were first capped with a layer of silica, followed by the decoration of silver nanoparticles, termed Ag@SiO2@Fe3O4, by using lemon fruit extract as the reducing agent in a size range of ∼90 nm. The effect of the green stabilizer on the characteristics of nanoparticles was examined via different spectroscopy techniques, and the elemental composition of the multilayer-coated structures was verified. The saturation magnetization of bare Fe3O4 nanoparticles at room temperature was recorded as 78.5 emu/g, whereas it decreased to 56.4 and 43.8 emu/g for silica coating and subsequent decoration with silver nanoparticles. All nanoparticles displayed superparamagnetic behavior with almost zero coercivity. While magnetization decreased with further coating processes, the specific surface area increased with silica coating from 67 to 180 m2 g-1 and decreased after the addition of silver and reached 98 m2 g-1, which can be explained by the organization of silver nanoparticles in an island-like model. Zeta potential values also decreased from -18 to -34 mV with coating, indicating an enhanced stabilization effect of the addition of silica and silver. The antibacterial tests against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) revealed that the bare Fe3O4 and SiO2@Fe3O4 did not show sufficient effect, while Ag@SiO2@Fe3O4, even at low concentrations (≤ 200 µg/mL), displayed high antibacterial activity due to the existence of silver atoms on the surface of nanoparticles. Furthermore, the in vitro cytotoxicity assay revealed that Ag@SiO2@Fe3O4 nanoparticles were not toxic to HSF-1184 cells at 200 µg/mL concentration. Antibacterial activity during consecutive magnetic separation and recycling steps was also investigated, and nanoparticles offered a high antibacterial effect for more than 10 cycles of recycling, making them potentially useful in biomedical fields.


Assuntos
Nanopartículas de Magnetita , Staphylococcus aureus , Prata/farmacologia , Prata/química , Dióxido de Silício/farmacologia , Dióxido de Silício/química , Nanopartículas de Magnetita/química , Escherichia coli , Antibacterianos/química
13.
Talanta ; 265: 124846, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37379752

RESUMO

Doxorubicin (DOX) is a highly effective anticancer drug with a narrow therapeutic window; thus, sensitive and timely detection of DOX is crucial. Using electrodeposition of silver nanoparticles (AgNPs) and electropolymerization of alginate (Alg) layers on the surface of a glassy carbon electrode, a novel electrochemical probe was constructed (GCE). The fabricated AgNPs/poly-Alg-modified GCE probe was utilized for the quantification of DOX in unprocessed human plasma samples. For the electrodeposition of AgNPs and electropolymerization of alginate (Alg) layers on the surface of GCE, cyclic voltammetry (CV) was used in the potential ranges of -2.0 to 2.0 V and -0.6 to 0.2 V, respectively. The electrochemical activity of DOX exhibited two oxidation processes at the optimum pH value of 5.5 on the surface of the modified GCE. The DPV spectra of poly(Alg)/AgNPs modified GCE probe toward consecutive concentrations of DOX in plasma samples demonstrated wide dynamic ranges of 15 ng/mL-0.1 µg/mL and 0.1-5.0 µg/mL, with a low limit of quantification (LLOQ) of 15 ng/mL. The validation results indicated that the fabricated electrochemical probe might serve as a highly sensitive and selective assay for the quantification of DOX in patient samples. As an outstanding feature, the developed probe could detect DOX in unprocessed plasma samples and cell lysates without the requirement for pretreatment.


Assuntos
Incrustação Biológica , Nanopartículas Metálicas , Humanos , Carbono , Doxorrubicina/análise , Prata , Incrustação Biológica/prevenção & controle , Eletrodos , Alginatos , Técnicas Eletroquímicas/métodos , Limite de Detecção
14.
ACS Biomater Sci Eng ; 9(7): 4138-4148, 2023 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-37311018

RESUMO

Polyethylene glycol (PEG) was utilized to functionalize the surface of zinc ferrite nanoparticles (NPs) synthesized by the hydrothermal process in order to prevent aggregation and improve the biocompatibility of the NPs for the proposed magnetic resonance imaging (MRI) agent. Various spectroscopy techniques were used to examine the NPs' structure, size, morphology, and magnetic properties. The NPs had a cubic spinel structure with an average size of 8 nm. The formations of the spinel ferrite and the PEG coating band at the ranges of 300-600 and 800-2000 cm-1, respectively, were validated by Fourier-transform infrared spectroscopy. The NPs were spherical in shape, and energy-dispersive X-ray spectroscopy with mapping confirmed the presence of zinc, iron, and oxygen in the samples. The results of high-resolution transmission electron microscopy revealed an average size of 14 nm and increased stability after PEG coating. The decrease in zeta potential from -24.5 to -36.5 mV confirmed the PEG coating on the surface of the NPs. A high saturation magnetization of ∼50 emu/g, measured by vibration sample magnetometer, indicated the magnetic potential of NPs for biomedical applications. An MTT assay was used to examine the cytotoxicity and viability of human normal skin cells (HSF 1184) exposed to zinc ferrite and PEG@Zn ferrite NPs at various concentrations. After 24 h of treatment, negligible cytotoxicity of PEG-coated NPs was observed at high concentrations. Magnetic resonance imaging (MRI) suggested that PEG@Zn ferrite NPs are a unique and perfectly suited contrast agent for T2-weighted MRI and can successfully enhance the image contrast.


Assuntos
Meios de Contraste , Nanopartículas , Humanos , Meios de Contraste/farmacologia , Meios de Contraste/química , Zinco , Polietilenoglicóis/química , Imageamento por Ressonância Magnética/métodos , Nanopartículas/química
15.
Front Immunol ; 14: 1064459, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37153613

RESUMO

The newly emerged coronavirus (SARS-CoV-2) is virulent, contagious, and has rapidly gained many mutations, which makes it highly infectious and swiftly transmissible around the world. SARS-CoV-2 infects people of all ages and targets all body organs and their cellular compartments, starting from the respiratory system, where it shows many deleterious effects, to other tissues and organs. Systemic infection can lead to severe cases that require intensive intervention. Multiple approaches were elaborated, approved, and successfully used in the intervention of the SARS-CoV-2 infection. These approaches range from the utilization of single and/or mixed medications to specialized supportive devices. For critically ill COVID-19 patients with acute respiratory distress syndrome, both extracorporeal membrane oxygenation (ECMO) and hemadsorption are utilized in combination or individually to support and release the etiological factors responsible for the "cytokine storm" underlying this condition. The current report discusses hemadsorption devices that can be used as part of supportive treatment for the COVID-19-associated cytokine storm.


Assuntos
COVID-19 , Oxigenação por Membrana Extracorpórea , Humanos , COVID-19/terapia , SARS-CoV-2 , Citocinas
16.
Med Res Rev ; 43(6): 2115-2176, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37165896

RESUMO

Breast cancer is the most malignant tumor in women, and there is no absolute cure for it. Although treatment modalities including surgery, chemotherapy, and radiotherapy are utilized for breast cancer, it is still a life-threatening disease for humans. Nanomedicine has provided a new opportunity in breast cancer treatment, which is the focus of the current study. The nanocarriers deliver chemotherapeutic agents and natural products, both of which increase cytotoxicity against breast tumor cells and prevent the development of drug resistance. The efficacy of gene therapy is boosted by nanoparticles and the delivery of CRISPR/Cas9, Noncoding RNAs, and RNAi, promoting their potential for gene expression regulation. The drug and gene codelivery by nanoparticles can exert a synergistic impact on breast tumors and enhance cellular uptake via endocytosis. Nanostructures are able to induce photothermal and photodynamic therapy for breast tumor ablation via cell death induction. The nanoparticles can provide tumor microenvironment remodeling and repolarization of macrophages for antitumor immunity. The stimuli-responsive nanocarriers, including pH-, redox-, and light-sensitive, can mediate targeted suppression of breast tumors. Besides, nanoparticles can provide a diagnosis of breast cancer and detect biomarkers. Various kinds of nanoparticles have been employed for breast cancer therapy, including carbon-, lipid-, polymeric- and metal-based nanostructures, which are different in terms of biocompatibility and delivery efficiency.


Assuntos
Neoplasias da Mama , Nanopartículas , Neoplasias , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Preparações Farmacêuticas , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Imunoterapia , Terapia Genética , Nanopartículas/química , Microambiente Tumoral
17.
Pathol Res Pract ; 246: 154482, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37196466

RESUMO

Breast cancer is the most frequently diagnosed malignancy in women and a major public health concern. In the current report, differential expression of the breast cancer resistance promoting genes with a focus on breast cancer stem cell related elements as well as the correlation of their mRNAs with various clinicopathologic characteristics, including molecular subtypes, tumor grade/stage, and methylation status, have been investigated using METABRIC and TCGA datasets. To achieve this goal, we downloaded gene expression data of breast cancer patients from TCGA and METABRIC. Then, statistical analyses were used to assess the correlation between the expression levels of stem cell related drug resistant genes and methylation status, tumor grades, various molecular subtypes, and some cancer hallmark gene sets such as immune evasion, metastasis, and angiogenesis. According to the results of this study, a number of stem cell related drug resistant genes are deregulated in breast cancer patients. Furthermore, we observe negative correlations between methylation of resistance genes and mRNA expression. There is a significant difference in the expression of resistance-promoting genes between different molecular subtypes. As mRNA expression and DNA methylation are clearly related, DNA methylation might be a mechanism that regulates these genes in breast cancer cells. As indicated by the differential expression of resistance-promoting genes among various breast cancer molecular subtypes, these genes may function differently in different subtypes of breast cancer. In conclusion, significant deregulation of resistance-promoting factors indicates that these genes may play a significant role in the development of breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Transcriptoma , Metilação de DNA , Células-Tronco Neoplásicas/patologia , Resistencia a Medicamentos Antineoplásicos , RNA Mensageiro/metabolismo , Regulação Neoplásica da Expressão Gênica
18.
Int J Biol Macromol ; 242(Pt 3): 124935, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37230442

RESUMO

The field of nanomedicine has provided a fresh approach to cancer treatment by addressing the limitations of current therapies and offering new perspectives on enhancing patients' prognoses and chances of survival. Chitosan (CS) is isolated from chitin that has been extensively utilized for surface modification and coating of nanocarriers to improve their biocompatibility, cytotoxicity against tumor cells, and stability. HCC is a prevalent kind of liver tumor that cannot be adequately treated with surgical resection in its advanced stages. Furthermore, the development of resistance to chemotherapy and radiotherapy has caused treatment failure. The targeted delivery of drugs and genes can be mediated by nanostructures in treatment of HCC. The current review focuses on the function of CS-based nanostructures in HCC therapy and discusses the newest advances of nanoparticle-mediated treatment of HCC. Nanostructures based on CS have the capacity to escalate the pharmacokinetic profile of both natural and synthetic drugs, thus improving the effectiveness of HCC therapy. Some experiments have displayed that CS nanoparticles can be deployed to co-deliver drugs to disrupt tumorigenesis in a synergistic way. Moreover, the cationic nature of CS makes it a favorable nanocarrier for delivery of genes and plasmids. The use of CS-based nanostructures can be harnessed for phototherapy. Additionally, the incur poration of ligands including arginylglycylaspartic acid (RGD) into CS can elevate the targeted delivery of drugs to HCC cells. Interestingly, smart CS-based nanostructures, including ROS- and pH-sensitive nanoparticles, have been designed to provide cargo release at the tumor site and enhance the potential for HCC suppression.


Assuntos
Carcinoma Hepatocelular , Quitosana , Neoplasias Hepáticas , Nanopartículas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Quitosana/química , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Medicina de Precisão , Nanopartículas/uso terapêutico , Nanopartículas/química
19.
Environ Res ; 228: 115912, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37068723

RESUMO

Nature-derived polymers, or biopolymers, are among the most employed materials for the development of nanocarriers. Chitosan (CS) is derived from the acetylation of chitin, and this biopolymer displays features such as biocompatibility, biodegradability, low toxicity, and ease of modification. CS-based nano-scale delivery systems have been demonstrated to be promising carriers for drug and gene delivery, and they can provide site-specific delivery of cargo. Owing to the high biocompatibility of CS-based nanocarriers, they can be used in the future in clinical trials. On the other hand, diabetes mellitus (DM) is a chronic disease that can develop due to a lack of insulin secretion or insulin sensitivity. Recently, CS-based nanocarriers have been extensively applied for DM therapy. Oral delivery of insulin is the most common use of CS nanoparticles in DM therapy, and they improve the pharmacological bioavailability of insulin. Moreover, CS-based nanostructures with mucoadhesive features can improve oral bioavailability of insulin. CS-based hydrogels have been developed for the sustained release of drugs and the treatment of DM complications such as wound healing. Furthermore, CS-based nanoparticles can mediate delivery of phytochemicals and other therapeutic agents in DM therapy, and they are promising compounds for the treatment of DM complications, including nephropathy, neuropathy, and cardiovascular diseases, among others. The surface modification of nanostructures with CS can improve their properties in terms of drug delivery and release, biocompatibility, and others, causing high attention to these nanocarriers in DM therapy.


Assuntos
Quitosana , Diabetes Mellitus , Nanopartículas , Nanoestruturas , Humanos , Quitosana/química , Sistemas de Liberação de Medicamentos , Nanoestruturas/química , Nanopartículas/química , Polímeros/química , Insulina , Diabetes Mellitus/tratamento farmacológico
20.
Environ Res ; 227: 115722, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-36948284

RESUMO

Nanomedicine is a field that combines biology and engineering to improve disease treatment, particularly in cancer therapy. One of the promising techniques utilized in this area is the use of micelles, which are nanoscale delivery systems that are known for their simple preparation, high biocompatibility, small particle size, and the ability to be functionalized. A commonly employed chemotherapy drug, Doxorubicin (DOX), is an effective inhibitor of topoisomerase II that prevents DNA replication in cancer cells. However, its efficacy is frequently limited by resistance resulting from various factors, including increased activity of drug efflux transporters, heightened oncogenic factors, and lack of targeted delivery. This review aims to highlight the potential of micelles as new nanocarriers for delivering DOX and to examine the challenges involved with employing chemotherapy to treat cancer. Micelles that respond to changes in pH, redox, and light are known as stimuli-responsive micelles, which can improve the targeted delivery of DOX and its cytotoxicity by facilitating its uptake in tumor cells. Additionally, micelles can be utilized to administer a combination of DOX and other drugs and genes to overcome drug resistance mechanisms and improve tumor suppression. Furthermore, micelles can be used in phototherapy, both photodynamic and photothermal, to promote cell death and increase DOX sensitivity in human cancers. Finally, the alteration of micelle surfaces with ligands can further enhance their targeted delivery for cancer suppression.


Assuntos
Doxorrubicina , Micelas , Humanos , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Concentração de Íons de Hidrogênio
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