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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 -
Biomaterials Advances Sep 2024Tumor microenvironment (TME)-responsive chemodynamic therapy (CDT) is severely hindered by insufficient intracellular HO level that seriously deteriorates antitumor...
Tumor microenvironment (TME)-responsive chemodynamic therapy (CDT) is severely hindered by insufficient intracellular HO level that seriously deteriorates antitumor efficacy, albeit with its extensively experimental and theoretical research. Herein, we designed atomically dispersed FeCo dual active sites anchored in porous carbon polyhedra (termed FeCo/PCP), followed by loading with glucose oxidase (GOx) and anticancer doxorubicin (DOX), named FeCo/PCP-GOx-DOX, which converted glucose into toxic hydroxyl radicals. The loaded GOx can either decompose glucose to self-supply HO or provide fewer nutrients to feed the tumor cells. The as-prepared nanozyme exhibited the enhanced in vitro cytotoxicity at high glucose by contrast with those at less or even free of glucose, suggesting sufficient accumulation of HO and continual transformation to OH for CDT. Besides, the FeCo/PCP-GOx-DOX can subtly integrate starvation therapy, the FeCo/PCP-initiated CDT, and DOX-inducible chemotherapy (CT), greatly enhancing the therapeutic efficacy than each monotherapy.
Topics: Hydrogen Peroxide; Doxorubicin; Glucose Oxidase; Humans; Animals; Tumor Microenvironment; Mice; Antineoplastic Agents; Cell Line, Tumor; Neoplasms; Glucose; Catalytic Domain
PubMed: 38861801
DOI: 10.1016/j.bioadv.2024.213919 -
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 -
Molecular Pharmaceutics Jul 2024Renal fibrosis plays a key role in the pathogenesis of chronic kidney disease (CKD), in which the persistent high expression of transforming growth factor β1 (TGF-β1)...
Renal fibrosis plays a key role in the pathogenesis of chronic kidney disease (CKD), in which the persistent high expression of transforming growth factor β1 (TGF-β1) and α-smooth muscle actin (α-SMA) contributes to the progression of CKD to renal failure. In order to improve the solubility, bioavailability, and targeting of tanshinone IIA (Tan IIA), a novel targeting material, aminoethyl anisamide-polyethylene glycol-1,2-distearoyl--glycero-3-phosphate ethanolamine (AEAA-PEG-DSPE, APD) modified Tan IIA liposomes (APD-Tan IIA-L) was constructed. An animal model of glomerulonephritis induced by doxorubicin in BALB/c mice was established. APD-Tan IIA-L significantly decreased blood urea nitrogen and serum creatinine (SCr), and the consequences of renal tissue oxidative stress indicators showed that APD-Tan IIA-L downregulated malondialdehyde, upregulated superoxide dismutase, catalase, and glutathione peroxidase. Masson's trichrome staining showed that the deposition of collagen in the APD-Tan IIA-L group decreased significantly. The pro-fibrotic factors (fibronectin, collagen I, TGF-β1, and α-SMA) and epithelial-mesenchymal transition marker (N-cadherin) were significantly inhibited by APD-Tan IIA-L. By improving the microenvironment of fibrotic kidneys, APD-Tan IIA-L attenuated TGF-β1-induced excessive proliferation of fibroblasts and alleviated oxidative stress damage to the kidney, providing a new strategy for the clinical treatment of renal fibrosis.
Topics: Animals; Doxorubicin; Mice; Liposomes; Abietanes; Fibrosis; Mice, Inbred BALB C; Kidney; Male; Glomerulonephritis; Transforming Growth Factor beta1; Oxidative Stress; Epithelial-Mesenchymal Transition; Disease Models, Animal; Renal Insufficiency, Chronic
PubMed: 38848439
DOI: 10.1021/acs.molpharmaceut.4c00042 -
Medicine Jun 2024Intestinal T-cell lymphomas are exceedingly rare diseases. Intestinal T-cell lymphoma NOS, as a "wastebasket" category, is difficult to diagnosis. Endoscopy can identify...
RATIONALE
Intestinal T-cell lymphomas are exceedingly rare diseases. Intestinal T-cell lymphoma NOS, as a "wastebasket" category, is difficult to diagnosis. Endoscopy can identify abnormal mucosa in most patients at a reasonably early stage. Therefore, it is crucial to increase the understanding of endoscopists in terms of the endoscopic characteristics of ITCL.
PATIENT CONCERNS
A 74-year-old male alone with wasting as the major complaint, had multiple polypoid lesions in the large intestine. The patient then had endoscopic care.
DIAGNOSES
Only 1 polypoid lesion on white-light endoscopy in the sigmoid colon was pathologically diagnosed as intestinal T-cell lymphomas, not otherwise specified (ITCL-NOS).
INTERVENTIONS
The patient underwent intensity-reduced CHOP therapy.
OUTCOMES
The patient is still with controlled disease but developed chemotherapy-related side effects.
LESSONS
In the individual with unexplained anemia and waste, endoscopy should not be delayed. For each of polypoid lesion on white-light endoscopy, the endoscopist need to remain cautious, because every lesion in the same patient can exhibit the independence of histopathological features. Meanwhile, we suggest that endoscopists should routinely observe the terminal ileum, even take biopsy samples if necessary.
Topics: Humans; Aged; Male; Antineoplastic Combined Chemotherapy Protocols; Lymphoma, T-Cell; Doxorubicin; Vincristine; Intestinal Neoplasms; Cyclophosphamide; Prednisone; Colonoscopy
PubMed: 38847694
DOI: 10.1097/MD.0000000000038465