Showing papers on "Doxorubicin published in 2022"

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma

Abstract: Diffuse large B-cell lymphoma (DLBCL) is typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, only 60% of patients are cured with R-CHOP. Polatuzumab vedotin is an antibody–drug conjugate targeting CD79b, which is ubiquitously expressed on the surface of malignant B cells.

Engineered neutrophil-derived exosome-like vesicles for targeted cancer therapy

Abstract: Neutrophil-derived exosomes induce tumor cell apoptosis by delivering cytotoxic proteins and activating caspase signaling pathway.

Fibronectin-Coated Metal-Phenolic Networks for Cooperative Tumor Chemo-/Chemodynamic/Immune Therapy via Enhanced Ferroptosis-Mediated Immunogenic Cell Death.

Abstract: The development of nanomedicine formulations to overcome the disadvantages of traditional chemotherapeutic drugs and integrate cooperative theranostic modes still remains challenging. Herein, we report the facile construction of a multifunctional theranostic nanoplatform based on doxorubicin (DOX)-loaded tannic acid (TA)-iron (Fe) networks (for short, TAF) coated with fibronectin (FN) for combination tumor chemo-/chemodynamic/immune therapy under the guidance of magnetic resonance (MR) imaging. We show that the DOX-TAF@FN nanocomplexes created through in situ coordination of TA and Fe(III) and physical coating with FN have a mean particle size of 45.0 nm, are stable, and can release both DOX and Fe in a pH-dependent manner. Due to the coexistence of the TAF network and DOX, significant immunogenic cell death can be caused through enhanced ferroptosis of cancer cells via cooperative Fe-based chemodynamic therapy and DOX chemotherapy. Through further treatment with programmed cell death ligand 1 antibody for an immune checkpoint blockade, the tumor treatment efficacy and the associated immune response can be further enhanced. Meanwhile, with FN-mediated targeting, the DOX-TAF@FN platform can specifically target tumor cells with high expression of αvβ3 integrin. Finally, the TAF network also enables the DOX-TAF@FN to have an r1 relaxivity of 6.1 mM-1 s-1 for T1-weighted MR imaging of tumors. The developed DOX-TAF@FN nanocomplexes may represent an updated multifunctional nanosystem with simple compositions for cooperative MR imaging-guided targeted chemo-/chemodynamic/immune therapy of tumors.

Intracellular Mutual Amplification of Oxidative Stress and Inhibition Multidrug Resistance for Enhanced Sonodynamic/Chemodynamic/Chemo Therapy.

Abstract: Emerging noninvasive treatments, such as sonodynamic therapy (SDT) and chemodynamic therapy (CDT), have developed as promising alternatives or supplements to traditional chemotherapy. However, their therapeutic effects are limited by the hypoxic environment of tumors. Here, a biodegradable nanocomposite-mesoporous zeolitic-imidazolate-framework@MnO2 /doxorubicin hydrochloride (mZMD) is developed, which achieves enhanced SDT/CDT/chemotherapy through promoting oxidative stress and overcoming the multidrug resistance. The mZMD decomposes under both ultrasound (US) irradiation and specific reactions in the tumor microenvironment (TME). The mZM composite structure reduces the recombination rate of e- and h+ to improve SDT. MnO2 not only oxidizes glutathione in tumor cells to enhance oxidative stress, but also converts the endogenic H2 O2 into O2 to improve the hypoxic TME, which enhances the effects of chemotherapy/SDT. Meanwhile, the generated Mn2+ catalyzes the endogenic H2 O2 into ·OH for CDT, and acts as magnetic resonance imaging agent to guide therapy. In addition, dissociated Zn2+ further breaks the redox balance of TME, and co-inhibits the expression of P-glycoprotein (P-gp) with generated ROS to overcome drug resistance. Thus, the as-prepared intelligent biodegradable mZMD provides an innovative strategy to enhance SDT/CDT/chemotherapy.

Preparation of a pH‐responsive chitosan‐montmorillonite‐nitrogen‐doped carbon quantum dots nanocarrier for attenuating doxorubicin limitations in cancer therapy

Abstract: Despite its widespread usage as a chemotherapy drug in cancer treatment, doxorubicin (DOX) has limitations such as short in vivo circulation time, low solubility, and poor permeability. In this regard, a pH‐responsive chitosan (CS)‐ montmorillonite (MMT)‐ nitrogen‐doped carbon quantum dots (NCQDs) nanocomposite was first developed, loaded with DOX, and then incorporated into a double emulsion to further develop the sustained release. The incorporated NCQDs into the CS‐MMT hydrogel exhibited enhanced loading and entrapment efficiencies. The presence of NCQDs nanoparticles in the CS‐MMT hydrogel also resulted in an extended pH‐responsive release of DOX over a period of 96 h compared to that of CS‐MMT‐DOX nanocarriers at pH 5.4. Based on the Korsmeyer‐Peppas model, there was a controlled DOX release at pH 5.4, while no diffusion was observed at pH 7.4, indicating fewer side effects. MTT assay showed that the cytotoxicity of DOX‐loaded CS‐MMT‐NCQDs hydrogel nanocomposite was significantly higher than those of free DOX (p < 0.001) and CS‐MMT‐NCQDs (p < 0.001) on MCF‐7 cells. Flow cytometry results demonstrated that a higher apoptosis induction achieved after incorporating NCQDs nanoparticles into CS‐MMT‐DOX nanocarrier. These findings suggest that the DOX‐loaded nanocomposite is a promising candidate for the targeted treatment of cancer cells.

Dual key co-activated nanoplatform for switchable MRI monitoring accurate ferroptosis-based synergistic therapy

Abstract: •Catalysis of CACN for ROS generation is “turned on” by co-activation of ATP and H+ •The accurate release of Dox can enhance the sensitivity of ferroptosis •ATP-triggered disassembly of CACN leads to high-sensitivity switchable MRI imaging •Switchable MRI can monitor ferroptosis-based therapy in combination with fluorescence Ferroptosis is of great significance for disease treatment and drug design because of its effective damage to drug-resistant cells. However, ferroptosis-based therapy presents challenges of low efficiency and low specificity, as well as the lack of reliable imaging technology for monitoring the therapeutic process. Herein, we have developed a tumor-microenvironment-tailored and co-activated catalytic nanoplatform (CACN) that was loaded with doxorubicin (Dox) molecules. Notably, the catalytic activity of CACN could be “turned on” for the specific ferroptosis treatment of cancer cells or tumors only upon co-activation by dual stimuli of ATP and slight acidity in the tumor microenvironment with the logic operation. Moreover, ATP-triggered disassembly of CACN led to the switchable MRI from negative to positive contrast, guaranteeing the sensitivity magnitude of MRI imaging. Furthermore, the switchable MRI signal is correlated with reactive oxygen species generation and Dox release, which is beneficial for monitoring the therapeutic process in combination with fluorescence imaging. Ferroptosis is of great significance for disease treatment and drug design because of its effective damage to drug-resistant cells. However, ferroptosis-based therapy presents challenges of low efficiency and low specificity, as well as the lack of reliable imaging technology for monitoring the therapeutic process. Herein, we have developed a tumor-microenvironment-tailored and co-activated catalytic nanoplatform (CACN) that was loaded with doxorubicin (Dox) molecules. Notably, the catalytic activity of CACN could be “turned on” for the specific ferroptosis treatment of cancer cells or tumors only upon co-activation by dual stimuli of ATP and slight acidity in the tumor microenvironment with the logic operation. Moreover, ATP-triggered disassembly of CACN led to the switchable MRI from negative to positive contrast, guaranteeing the sensitivity magnitude of MRI imaging. Furthermore, the switchable MRI signal is correlated with reactive oxygen species generation and Dox release, which is beneficial for monitoring the therapeutic process in combination with fluorescence imaging.

Metal‐organic frameworks encapsulated with an anticancer compound as drug delivery system: Synthesis, characterization, antioxidant, anticancer, antibacterial and molecular docking investigation

Abstract: Metal organic framework (MOF) hybrid materials could be one of the answers in this investigation. We describe a simple and effective encapsulation of doxorubicin (DOX), an anticancer drug, inside Zr-MOF, which have been little studied as drug delivery organizations. We investigated the measured release of the drug from Zr-MOF in response to external incentives such as pH changes and interaction with biomimetic schemes. Zr-MOF with encapsulated doxorubicin (DOX@Zr-MOF) can be manufactured in one pot by addition the anticancer medication DOX to the reaction combination. They demonstrated pH-responsive medication release and cancer cell killing capability. MOFs can be designed as multifunctional distribution vehicles for a diversity of loads, including medicinal and imaging agents, using our simple one-pot approach. Fourier transform infrared (FTIR), X-ray diffraction, scanning electron microscopy, and N-2 sorption isotherm were used to analyze MOF and the developed drug delivery (DOX@Zr-MOF) scheme. It investigated the effects of MOF and a bespoke drug delivery system on the feasibility of patient breast as well as liver tumor cell lines. At pH 5, the trapped drug can be released more quickly than at pH 7.4. Zr-MOF nanoparticles had modest cytotoxicity;however, DOX@Zr-MOF has higher cytotoxicity in MCF-7 and HepG-2 cells than DOX at concentrations greater than 31.25 mu g ml(-1). These results were discovered that DOX@Zr-MOF could be a promising technique for delivering medicines to cancer cells. Furthermore, using the agar well dispersion technique, Zr-MOF, DOX, and captured DOX@Zr-MOF samples were assessed for their potential antibacterial activity against pathogenic bacteria in comparison to traditional antibiotics. In compared to the reference medication Gentamycin, the DOX@Zr-MOF exhibits a large inhibitory zone against Gram negative organisms (Escherichia coli). The docking active place interactions were assessed to see if DOX might bind to the breast cancer 3hb5-oxidoreductase receptor, prostate cancer protein 2q7k, and SARS-CoV-2 protease 6YB7 for anticancer and anticovid-19 activities.

Self‐Sacrificially Degradable Pseudo‐Semiconducting Polymer Nanoparticles that Integrate NIR‐II Fluorescence Bioimaging, Photodynamic Immunotherapy, and Photo‐Activated Chemotherapy

Abstract: Semiconducting polymers (SP) hold great promise for cancer phototherapy due to their excellent optical properties; however, their clinical application is still hampered by their poor biodegradability. Herein, a self‐sacrificially biodegradable pseudo‐semiconducting polymer (PSP) for NIR‐II fluorescence bioimaging, photodynamic immunotherapy, and photoactivated chemotherapy (PACT) is reported. The PSP can further co‐assemble with an amphiphilic polyester with pendant doxorubicin (DOX) in its side chains via reactive oxygen species (ROS)‐responsive thioketal linkages (PEDOX), which are denoted as NP@PEDOX/PSP. The NP@PEDOX/PSP can accumulate at tumor sites and generate ROS for photodynamic immunotherapy as well as near‐infrared‐II fluorescence (NIR‐II) for bioimaging upon irradition at 808 nm. The ROS could break up thioketal linkages in PEDOX, resulting in rapid doxorubicin (DOX) release for PACT. Finally, both PEDOX and PSP are degraded sacrificially by intracellular glutathione (GSH), resulting in the dissociation of NP@PEDOX/PSP. This work highlights the application of self‐sacrificially degradable PSP for NIR‐II fluorescence bioimaging, photodynamic immunotherapy, and PACT in cancer therapy.

Doxorubicin-loaded graphene oxide nanocomposites in cancer medicine: stimuli-responsive carriers, co-delivery and suppressing resistance

Abstract: ABSTRACT Introduction The application of doxorubicin (DOX) in cancer therapy has been limited due to its drug resistance and poor internalization. Graphene oxide (GO) nanostructures have the capacity for DOX delivery while promoting its cytotoxicity in cancer. Areas covered The favorable characteristics of GO nanocomposites, preparation method, and application in cancer therapy are described. Then, DOX resistance in cancer, GO-mediated photothermal therapy, and DOX delivery for cancer suppression are described. Preparation of stimuli-responsive GO nanocomposites, surface functionalization, hybrid nanoparticles, and theranostic applications are emphasized in DOX chemotherapy. Expert opinion GO nanoparticle-based photothermal therapy maximizes the anti-cancer activity of DOX against cancer cells. Besides DOX delivery, GO nanomaterials are capable of loading anti-cancer agents and genetic tools to minimize drug resistance and enhance the cytolytic impact of DOX in cancer eradication. To enhance DOX accumulation, stimuli-responsive (redox-, light-, enzyme- and pH-sensitive) GO nanoparticles have been developed for DOX delivery. Development of targeted delivery of DOX-loaded GO nanomaterials against cancer cells may be achieved by surface modification of polymers such as polyethylene glycol, hyaluronic acid, and chitosan. DOX-loaded GO nanoparticles have demonstrated theranostic potential. Hybridization of GO with other nanocarriers such as silica and gold nanoparticles further broadens their potential anti-cancer therapy applications. Graphical abstract: The graphene oxide nanomaterials for doxorubicin delivery in improving its cytotoxicity, providing a platform for co-delivery, theranostic application and preventing drug resistance development

Underlying the Mechanisms of Doxorubicin-Induced Acute Cardiotoxicity: Oxidative Stress and Cell Death

Abstract: Cancer is a destructive disease that causes high levels of morbidity and mortality. Doxorubicin (DOX) is a highly efficient antineoplastic chemotherapeutic drug, but its use places survivors at risk for cardiotoxicity. Many studies have demonstrated that multiple factors are involved in DOX-induced acute cardiotoxicity. Among them, oxidative stress and cell death predominate. In this review, we provide a comprehensive overview of the mechanisms underlying the source and effect of free radicals and dependent cell death pathways induced by DOX. Hence, we attempt to explain the cellular mechanisms of oxidative stress and cell death that elicit acute cardiotoxicity and provide new insights for researchers to discover potential therapeutic strategies to prevent or reverse doxorubicin-induced cardiotoxicity.

A Nanoarchitectonic Approach Enables Triple Modal Synergistic Therapies To Enhance Antitumor Effects.

Abstract: Improvement of antitumor effects relies on the development of biocompatible nanomaterials and combination of various therapies to produce synergistic effects and avoid resistance. In this work, we developed GBD-Fe, a nanoformulation that effectively integrated chemotherapy (CT), chemodynamic therapy (CDT), and photothermal therapy (PTT). GBD-Fe used gold nanorods as photothermal agents and encapsulated doxorubicin to amplify Fe3+-guided CDT effects by producing H2O2 and reducing the intracellular glutathione levels. In vitro and in vivo experiments were conducted to demonstrate the enhanced accumulation and antitumor effects of this tripronged therapy under magnetic resonance imaging (MRI) guidance. This tripronged approach of CT/CDT/PTT effectively induced tumor cytotoxicity and inhibited tumor growth in tumor-bearing mice and therefore represents a promising strategy to effectively treat tumors.

Light‐Triggered Efficient Sequential Drug Delivery of Biomimetic Nanosystem for Multimodal Chemo‐, Antiangiogenic, and Anti‐MDSC Therapy in Melanoma

Abstract: In view of the multiple pathological hallmarks of tumors, nanosystems for the sequential delivery of various drugs whose targets are separately located inside and outside tumor cells are desired for improved cancer therapy. However, current sequential delivery is mainly achieved through enzyme‐ or acid‐dependent degradation of the nanocarrier, which would be influenced by the heterogeneous tumor microenvironment, and unloading efficiency of the drug acting on the target outside tumor cells is usually unsatisfactory. Here, a light‐triggered sequential delivery strategy based on a liposomal formulation of doxorubicin (DOX)‐loaded small‐sized polymeric nanoparticles (DOX‐NP) and free sunitinib in the aqueous cavity, is developed. The liposomal membrane is doped with photosensitizer porphyrin–phospholipid (PoP) and hybridized with red blood cell membrane to confer biomimetic features. Near‐infrared light‐induced membrane permeabilization triggers the “ultrafast” and “thorough” release of sunitinib (100% release in 5 min) for antiangiogenic therapy and also myeloid‐derived suppressor cell (MDSC) inhibition to reverse the immunosuppressive tumor environment. Subsequently, the small‐sized DOX‐NP liberated from the liposomes is more easily uptaken by tumor cells for improved immunogenic chemotherapy. RNA sequencing and immune‐related assay indicates therapeutic immune enhancement. This light‐triggered sequential delivery strategy demonstrates the potency in cancer multimodal therapy against multiple targets in different spatial positions in tumor microenvironment.

Encapsulation, Release, and Cytotoxicity of Doxorubicin Loaded in Liposomes, Micelles, and Metal-Organic Frameworks: A Review

Abstract: Doxorubicin (DOX) is one of the most widely used anthracycline anticancer drugs due to its high efficacy and evident antitumoral activity on several cancer types. However, its effective utilization is hindered by the adverse side effects associated with its administration, the detriment to the patients’ quality of life, and general toxicity to healthy fast-dividing cells. Thus, delivering DOX to the tumor site encapsulated inside nanocarrier-based systems is an area of research that has garnered colossal interest in targeted medicine. Nanoparticles can be used as vehicles for the localized delivery and release of DOX, decreasing the effects on neighboring healthy cells and providing more control over the drug’s release and distribution. This review presents an overview of DOX-based nanocarrier delivery systems, covering loading methods, release rate, and the cytotoxicity of liposomal, micellar, and metal organic frameworks (MOFs) platforms.

Mitochondrial-Targeted Therapy for Doxorubicin-Induced Cardiotoxicity

Abstract: Anthracyclines, such as doxorubicin, are effective chemotherapeutic agents for the treatment of cancer, but their clinical use is associated with severe and potentially life-threatening cardiotoxicity. Despite decades of research, treatment options remain limited. The mitochondria is commonly considered to be the main target of doxorubicin and mitochondrial dysfunction is the hallmark of doxorubicin-induced cardiotoxicity. Here, we review the pathogenic mechanisms of doxorubicin-induced cardiotoxicity and present an update on cardioprotective strategies for this disorder. Specifically, we focus on strategies that can protect the mitochondria and cover different therapeutic modalities encompassing small molecules, post-transcriptional regulators, and mitochondrial transfer. We also discuss the shortcomings of existing models of doxorubicin-induced cardiotoxicity and explore advances in the use of human pluripotent stem cell derived cardiomyocytes as a platform to facilitate the identification of novel treatments against this disorder.

Stimuli‐Sensitive Linear–Dendritic Block Copolymer–Drug Prodrug as a Nanoplatform for Tumor Combination Therapy

Abstract: Linear-dendritic block copolymer (LDBCs) are highly attractive candidates for smart drug-delivery vehicles. Herein, an amphiphilic poly[(ethylene glycol) methyl ether methacrylate] (POEGMA) linear-peptide dendritic prodrug of doxorubicin (DOX) prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization is reported. The hydrophobic-dye-based photosensitizer chlorin e6 (Ce6) is employed for encapsulation in the prodrug nanoparticles (NPs) to obtain an LDBCs-based drug-delivery system (LD-DOX/Ce6) that offers a combination cancer therapy. Due to the presence of Gly-Phe-Leu-Gly peptides and hydrazone bonds in the prodrug structure, LD-DOX/Ce6 is degraded into small fragments, thus specifically triggering the intracellular release of DOX and Ce6 in the tumor microenvironment. Bioinformatics analysis suggests that LD-DOX/Ce6 with laser irradiation treatment significantly induces apoptosis, DNA damage, and cell cycle arrest. The combination treatment can not only suppress tumor growth, but also significantly reduce tumor metastasis compared with treatments with DOX or Ce6 through regulating EMT pathway, TGFβ pathway, angiogenesis, and the hypoxia pathway. LD-DOX/Ce6 displays a synergistic chemo-photodynamic antitumor efficacy, resulting in a high inhibition in tumor growth and metastasis, while maintaining an excellent biosafety. Therefore, this study demonstrates the potential of the biodegradable and tumor-microenvironment-responsive LDBCs as an intelligent multifunctional drug-delivery vehicle for high-efficiency cancer combination therapy.