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Biomedicine & Pharmacotherapy =... Jul 2024DNA repair allows the survival of cancer cells. Therefore, the development of DNA repair inhibitors is a critical need for sensitizing cancers to chemoradiation. Sae2...
BACKGROUND
DNA repair allows the survival of cancer cells. Therefore, the development of DNA repair inhibitors is a critical need for sensitizing cancers to chemoradiation. Sae2 has specific functions in initiating DNA end resection, as well as coordinating cell cycle checkpoints, and it also greatly interacts with the DDR at different levels.
RESULTS
In this study, we demonstrated that corylin, a potential sensitizer, causes deficiencies in DNA repair and DNA damage checkpoints in yeast cells. More specifically, corylin increases DNA damage sensitivity through the Sae2-dependent pathway and impairs the activation of Mec1-Ddc2, Rad53-p and γ-H2A. In breast cancer cells, corylin increases apoptosis and reduces proliferation following Dox treatment by inhibiting CtIP. Xenograft assays showed that treatment with corylin combined with Dox significantly reduced tumor growth in vivo.
CONCLUSIONS
Our findings herein delineate the mechanisms of action of corylin in regulating DNA repair and indicate that corylin has potential long-term clinical utility as a DDR inhibitor.
Topics: DNA Damage; Humans; Animals; DNA Repair; Homologous Recombination; Xenograft Model Antitumor Assays; Female; Mice, Nude; Cell Line, Tumor; Apoptosis; Cell Proliferation; Saccharomyces cerevisiae; Doxorubicin; Mice; Mice, Inbred BALB C; Saccharomyces cerevisiae Proteins
PubMed: 38865847
DOI: 10.1016/j.biopha.2024.116864 -
Revista Da Associacao Medica Brasileira... 2024Chemotherapy with doxorubicin may lead to left ventricular dysfunction. There is a controversial recommendation that biomarkers can predict ventricular dysfunction,... (Observational Study)
Observational Study
BACKGROUND
Chemotherapy with doxorubicin may lead to left ventricular dysfunction. There is a controversial recommendation that biomarkers can predict ventricular dysfunction, which is one of the most feared manifestations of anthracycline cardiotoxicity.
OBJECTIVE
The aim of this study was to evaluate the behavior of biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin in predicting cardiotoxicity in a cohort of women with breast cancer undergoing chemotherapy with anthracycline.
METHODS
This is an observational, prospective, longitudinal, unicentric study, which included 40 women with breast cancer, whose therapeutic proposal included treatment with doxorubicin. The protocol had a clinical follow-up of 12 months. Biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin were measured pre-chemotherapy and after the first, third, fourth, and sixth cycles of chemotherapy.
RESULTS
There was a progressive increase in type B natriuretic peptide and myoglobin values in all chemotherapy cycles. Although creatine phosphokinase fraction MB showed a sustained increase, this increase was not statistically significant. Troponin, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB were the cardiotoxicity markers with the earliest changes, with a significant increase after the first chemotherapy session. However, they were not able to predict cardiotoxicity.
CONCLUSION
Troponin I, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB are elevated during chemotherapy with doxorubicin, but they were not able to predict cardiotoxicity according to established clinical and echocardiographic criteria. The incidence of subclinical cardiotoxicity resulting from the administration of doxorubicin was 12.5%.
Topics: Humans; Female; Breast Neoplasms; Prospective Studies; Troponin I; Doxorubicin; Cardiotoxicity; Middle Aged; Biomarkers; Myoglobin; Adult; Antibiotics, Antineoplastic; Natriuretic Peptide, Brain; Aged; Creatine Kinase, MB Form; Longitudinal Studies; Anthracyclines; Ventricular Dysfunction, Left; Predictive Value of Tests
PubMed: 38865526
DOI: 10.1590/1806-9282.2024S106 -
Science Advances Jun 2024Lung metastasis poses a formidable challenge in the realm of cancer treatment, with conventional chemotherapy often falling short due to limited targeting and low...
Lung metastasis poses a formidable challenge in the realm of cancer treatment, with conventional chemotherapy often falling short due to limited targeting and low accumulation in the lungs. Here, we show a microrobot approach using motile algae for localized delivery of drug-loaded nanoparticles to address lung metastasis challenges. The biohybrid microrobot [denoted "algae-NP(DOX)-robot"] combines green microalgae with red blood cell membrane-coated nanoparticles containing doxorubicin, a representative chemotherapeutic drug. Microalgae provide autonomous propulsion in the lungs, leveraging controlled drug release and enhanced drug dispersion to exert antimetastatic effects. Upon intratracheal administration, algae-NP(DOX)-robots efficiently transport their drug payload deep into the lungs while maintaining continuous motility. This strategy leads to rapid drug distribution, improved tissue accumulation, and prolonged retention compared to passive drug-loaded nanoparticles and free drug controls. In a melanoma lung metastasis model, algae-NP(DOX)-robots exhibit substantial improvement in therapeutic efficacy, reducing metastatic burden and extending survival compared to control groups.
Topics: Lung Neoplasms; Animals; Doxorubicin; Nanoparticles; Mice; Cell Line, Tumor; Humans; Drug Delivery Systems; Microalgae; Robotics; Disease Progression; Antineoplastic Agents
PubMed: 38865468
DOI: 10.1126/sciadv.adn6157 -
Drug Design, Development and Therapy 2024In the era of single and combination maintenance therapies as well as platinum and Poly (ADP-ribose) polymerase inhibitors (PARPi) resistance, the choice of subsequent... (Review)
Review
In the era of single and combination maintenance therapies as well as platinum and Poly (ADP-ribose) polymerase inhibitors (PARPi) resistance, the choice of subsequent treatments following first-line platinum-based chemotherapy in recurrent ovarian cancer (ROC) patients has become increasingly complex. Within the ovarian cancer treatment algorithm, particularly in the emerging context of PARPi resistance, the role of trabectedin, in combination with pegylated liposomal doxorubicin (PLD) still preserves its significance. This paper offers valuable insights into the multifaceted role and mechanism of action of trabectedin in ROC. The main results of clinical trials and studies involving trabectedin/PLD, along with hints of Breast Cancer genes (BRCA)-mutated and BRCAness phenotype cases, are critically discussed. Moreover, this review provides and contextualizes potential scenarios of administering trabectedin in combination with PLD in ROC, according to established guidelines and beyond.
Topics: Trabectedin; Humans; Ovarian Neoplasms; Female; Antineoplastic Agents, Alkylating; Tetrahydroisoquinolines; Dioxoles; Doxorubicin; Polyethylene Glycols; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38863768
DOI: 10.2147/DDDT.S451223 -
Nanotechnology Jun 2024Extracellular vesicles (EVs) have great potential in oncology drug delivery because of their unique biological origin. Apoptotic bodies (ABs), as a member of the EV...
Extracellular vesicles (EVs) have great potential in oncology drug delivery because of their unique biological origin. Apoptotic bodies (ABs), as a member of the EV family, offer distinct advantages in terms of size, availability and membrane properties, but have been neglected for a long time. Here, using ABs and TiN nanosheets, we propose a novel drug delivery system (TiN-DOX@ABs), which exhibit a homologous targeting ability for dual-strategy tumor therapy with intrinsic biological property. The experimental results demonstrate that such a drug delivery system possesses a drug loading capacity of 496.5% and a near-infrared photothermal conversion efficiency of 38.4%. In addition, the investigation of drug internalization process proved that TiN-DOX@ABs featured a supreme biocompatibility. Finally, the dual-strategy response based on photothermal and chemotherapeutic effects was studied under near-infrared laser radiation. This work explores the opportunity of apoptosome membranes in nanomedicine systems, which provides a technical reference for cancer-oriented precision medicine research.
Topics: Humans; Photothermal Therapy; Titanium; Doxorubicin; Drug Delivery Systems; Nanostructures; Cell Line, Tumor; Extracellular Vesicles; Antineoplastic Agents; Apoptosis; Infrared Rays; Animals; Cell Survival
PubMed: 38861968
DOI: 10.1088/1361-6528/ad5690 -
Optics Express May 2024Doxorubicin (DOX) is an important drug for cancer treatment, but its clinical application is limited due to its toxicity and side effects. Therefore, detecting the...
Development of a biophotonic fiber sensor using direct-taper and anti-taper techniques with seven-core and four-core fiber for the detection of doxorubicin in cancer treatment.
Doxorubicin (DOX) is an important drug for cancer treatment, but its clinical application is limited due to its toxicity and side effects. Therefore, detecting the concentration of DOX during treatment is crucial for enhancing efficacy and reducing side effects. In this study, the authors developed a biophotonic fiber sensor based on localized surface plasmon resonance (LSPR) with the multimode fiber (MMF)-four core fiber (FCF)-seven core fiber (SCF)-MMF-based direct-taper and anti-taper structures for the specific detection of DOX. Compared to other detection methods, it has the advantages of high sensitivity, low cost, and strong anti-interference ability. In this experiment, multi-walled carbon nanotubes (MWCNTs), cerium-oxide nanorods (CeO-NRs), and gold nanoparticles (AuNPs) were immobilized on the probe surface to enhance the sensor's biocompatibility. MWCNTs and CeO-NRs provided more binding sites for the fixation of AuNPs. By immobilizing AuNPs on the surface, the LSPR was stimulated by the evanescent field to detect DOX. The sensor surface was functionalized with DOX aptamers for specific detection, enhancing its specificity. The experiments demonstrated that within a linear detection range of 0-10 µM, the sensitivity of the sensor is 0.77 nm/µM, and the limit of detection (LoD) is 0.42 µM. Additionally, the probe's repeatability, reproducibility, stability, and selectivity were evaluated, indicating that the probe has high potential for detecting DOX during cancer treatment.
Topics: Doxorubicin; Humans; Surface Plasmon Resonance; Gold; Metal Nanoparticles; Neoplasms; Nanotubes, Carbon; Biosensing Techniques; Optical Fibers; Equipment Design; Antibiotics, Antineoplastic; Cerium; Fiber Optic Technology
PubMed: 38858913
DOI: 10.1364/OE.525125 -
Scientific Reports Jun 2024Liver cancer ranks as the fifth leading cause of cancer-related death globally. Direct intratumoral injections of anti-cancer therapeutics may improve therapeutic...
Liver cancer ranks as the fifth leading cause of cancer-related death globally. Direct intratumoral injections of anti-cancer therapeutics may improve therapeutic efficacy and mitigate adverse effects compared to intravenous injections. Some challenges of intratumoral injections are that the liquid drug formulation may not remain localized and have unpredictable volumetric distribution. Thus, drug delivery varies widely, highly-dependent upon technique. An X-ray imageable poloxamer 407 (POL)-based drug delivery gel was developed and characterized, enabling real-time feedback. Utilizing three needle devices, POL or a control iodinated contrast solution were injected into an ex vivo bovine liver. The 3D distribution was assessed with cone beam computed tomography (CBCT). The 3D distribution of POL gels demonstrated localized spherical morphologies regardless of the injection rate. In addition, the gel 3D conformal distribution could be intentionally altered, depending on the injection technique. When doxorubicin (DOX) was loaded into the POL and injected, DOX distribution on optical imaging matched iodine distribution on CBCT suggesting spatial alignment of DOX and iodine localization in tissue. The controllability and localized deposition of this formulation may ultimately reduce the dependence on operator technique, reduce systemic side effects, and facilitate reproducibility across treatments, through more predictable standardized delivery.
Topics: Hydrogels; Animals; Doxorubicin; Drug Delivery Systems; Poloxamer; Cattle; Cone-Beam Computed Tomography; Needles; Liver
PubMed: 38858467
DOI: 10.1038/s41598-024-64189-z -
Carbohydrate Polymers Sep 2024Targeted and stimuli-responsive drug delivery enhances therapeutic efficacy and minimizes undesirable side effects of cancer treatment. Although cellulose nanocrystals...
Targeted and stimuli-responsive drug delivery enhances therapeutic efficacy and minimizes undesirable side effects of cancer treatment. Although cellulose nanocrystals (CNCs) are used as drug carriers because of their robustness, spindle shape, biocompatibility, renewability, and nontoxicity, the lack of programmability and functionality of CNCs-based platforms hampers their application. Thus, high adaptability and the capacity to form dynamic 3D nanostructures of DNA may be advantageous, as they can provide functionalities such as target-specific and stimuli-responsive drug release. Using DNA nanotechnology, the functional polymeric form of DNA nanostructures can be replicated using rolling circle amplification (RCA), and the biologically and physiologically stable DNA nanostructures may overcome the challenges of CNCs. In this study, multifunctional polymeric DNAs produced with RCA were strongly complexed with surface-modified CNCs via electrostatic interactions to form polymeric DNA-decorated CNCs (pDCs). Particle size, polydispersity, zeta potential, and biostability of the nanocomplexes were analyzed. As a proof of concept, the dynamic structural functionalities of DNA nanostructures were verified by observing cancer-targeted intracellular delivery and pH-responsive drug release. pDCs showed anticancer properties without side effects in vitro, owing to their aptamer and i-motif functionalities. In conclusion, pDCs exhibited multifunctional anticancer activities, demonstrating their potential as a promising hybrid nanocomplex platform for targeted cancer therapy.
Topics: Cellulose; Humans; Nanoparticles; DNA; Drug Liberation; Nanostructures; Drug Carriers; Drug Delivery Systems; Antineoplastic Agents; Polymers; Hydrogen-Ion Concentration; Doxorubicin; Cell Survival
PubMed: 38858000
DOI: 10.1016/j.carbpol.2024.122270 -
International Journal of Nanomedicine 2024Breast cancer is a prevalent malignancy among women worldwide, and malignancy is closely linked to the tumor microenvironment (TME). Here, we prepared mixed nano-sized...
PURPOSE
Breast cancer is a prevalent malignancy among women worldwide, and malignancy is closely linked to the tumor microenvironment (TME). Here, we prepared mixed nano-sized formulations composed of pH-sensitive liposomes (Ber/Ru486@CLPs) and small-sized nano-micelles (Dox@CLGs). These liposomes and nano-micelles were modified by chondroitin sulfate (CS) to selectively target breast cancer cells.
METHODS
Ber/Ru486@CLPs and Dox@CLGs were prepared by thin-film dispersion and ethanol injection, respectively. To mimic actual TME, the in vitro "condition medium of fibroblasts + MCF-7" cell model and in vivo "4T1/NIH-3T3" co-implantation mice model were established to evaluate the anti-tumor effect of drugs.
RESULTS
The physicochemical properties showed that Dox@CLGs and Ber/Ru486@CLPs were 28 nm and 100 nm in particle size, respectively. In vitro experiments showed that the mixed formulations significantly improved drug uptake and inhibited cell proliferation and migration. The in vivo anti-tumor studies further confirmed the enhanced anti-tumor capabilities of Dox@CLGs + Ber/Ru486@CLPs, including smaller tumor volumes, weak collagen deposition, and low expression levels of α-SMA and CD31 proteins, leading to a superior anti-tumor effect.
CONCLUSION
In brief, this combination therapy based on Dox@CLGs and Ber/Ru486@CLPs could effectively inhibit tumor development, which provides a promising approach for the treatment of breast cancer.
Topics: Tumor Microenvironment; Animals; Female; Breast Neoplasms; Humans; Mice; Liposomes; MCF-7 Cells; Doxorubicin; Cell Proliferation; Mice, Inbred BALB C; NIH 3T3 Cells; Chondroitin Sulfates; Particle Size; Nanoparticle Drug Delivery System; Drug Delivery Systems; Cell Movement; Nanoparticles
PubMed: 38855730
DOI: 10.2147/IJN.S460874 -
International Journal of Radiation... Jul 2024
Topics: Humans; Lymphoma, Large B-Cell, Diffuse; Neoplasm Recurrence, Local; Antineoplastic Combined Chemotherapy Protocols; Lymph Node Excision; Lymph Nodes; Doxorubicin
PubMed: 38851269
DOI: 10.1016/j.ijrobp.2024.01.228