doxorubicin

Overview

Doxorubicin is an anthracycline anticancer drug widely used in chemotherapy for a broad range of malignancies, including breast cancer, lymphoma, sarcoma, leukemia, and other solid tumors. Its principal antitumor activity is associated with DNA intercalation and inhibition of topoisomerase II, leading to DNA damage, impaired replication, and apoptosis. Doxorubicin is also notable for its intrinsic fluorescence, which makes it useful as a model compound in drug-delivery and imaging studies.

Despite its established efficacy, doxorubicin is limited by dose-dependent toxicities, especially cardiotoxicity, and by the emergence of tumor resistance. These limitations have made it a central focus of research in nanomedicine, prodrug design, combination therapy, and mechanistic studies of resistance, oxidative stress, ferroptosis, apoptosis, and tumor microenvironment remodeling.

Focus of Latest Publications

Recent publications continue to use doxorubicin as both a therapeutic benchmark and a formulation target in oncology research. Several studies focused on improving its delivery through nanotechnology and stimulus-responsive systems. Examples include hyaluronic acid-based electro-responsive hydrogels, pH- and glutathione-responsive nanozymes, ROS-responsive nanoparticles, thermosensitive liposomes, and biomimetic carriers. These platforms were designed to increase local drug release in the tumor microenvironment while limiting systemic exposure. Related work used folic acid-targeted PLGA nanoparticles, chondroitin sulfate-functionalized lipid nanoparticles, calcium phosphate lipid nanoparticles, and exosome-based systems to co-deliver doxorubicin with other agents such as Bcl-2 siRNA, nifuroxazide, MnTPP, bufalin, vitamin E, or STING agonists. Across these studies, doxorubicin was commonly paired with targeting ligands or stimuli-responsive linkers to improve tumor accumulation and trigger release under acidic, redox-active, or externally controlled conditions.

A major theme in the recent literature is combination therapy. Doxorubicin was co-formulated or co-administered with cyclophosphamide, vincristine, carboplatin, paclitaxel, cisplatin, temozolomide, olaparib, and other anticancer agents in efforts to improve efficacy or overcome resistance. In breast cancer, doxorubicin was studied in triple-negative breast cancer models, including MDA-MB-231 and MCF-7 breast cancer cells, where it was combined with bufalin, vitamin E, nisin, bakuchiol, or pembrolizumab-containing neoadjuvant regimens. In lymphoma and sarcoma contexts, doxorubicin remained part of standard multi-agent protocols such as Pola-R-CHP, N-AVD, VDC, and Ewing-like regimens. In some studies, doxorubicin served as a comparator to assess the potency of new compounds, including topoisomerase-targeting derivatives, CDK4 inhibitors, and other experimental anticancer molecules.

Mechanistically, several studies examined doxorubicin-induced cell death pathways and resistance biology. Doxorubicin was linked to immunogenic cell death, apoptosis, ferroptosis, mitotic slippage, and DNA damage responses. Some studies investigated how pulsed electromagnetic fields, nitric oxide-enhanced nanosystems, or engineered bacteria-mediated delivery could potentiate doxorubicin’s effects. Others explored resistance mechanisms, including paxillin-associated doxorubicin resistance, nuclear XIAP-linked chemoresistance, SLC44A4-associated sensitivity to DNA-damaging agents, and tumor endothelial cell reprogramming that reduces doxorubicin efficacy. These findings reinforce doxorubicin’s role as a central probe for studying chemotherapy response and resistance in cancer biology.

Doxorubicin also remained a key subject in toxicity and supportive-care research. Multiple studies addressed doxorubicin-induced cardiotoxicity, cardiomyopathy, neurotoxicity, and endothelial injury. Cardioprotective interventions included carvacrol, Vas2870, and Guizhi Gancao Decoction, with mechanistic attention to Nrf2/Keap1 signaling, microtubule acetylation, and ferroptosis-related pathways. In non-human and veterinary contexts, doxorubicin was reported as a rescue agent in dogs with presumed neoplastic hemorrhage, underscoring its continued use beyond human oncology. Overall, the recent literature portrays doxorubicin as both a clinically indispensable chemotherapeutic and a versatile experimental tool for developing targeted delivery systems, combination regimens, and toxicity-mitigation strategies.

Key Publications

• NEWApr A general tyrosinase-responsive prodrug strategy: design and synthesis of melanoma-selective anticancer agents. (Bioorganic & medicinal chemistry, 2026, PMID 41955916): "By introducing a TYR-specific recognition unit into the molecular structures of doxorubicin (DOX) and camptothecin (CPT) and coupling them via a self-immolative linker, two potential prodrugs, TYR-DOX and TYR-CPT, were successfully designed and synthesized."
• NEWJul Electrically controlled hyaluronic acid-based hydrogel for sustained and repeatable metronomic chemotherapy. (Biomaterials, 2026, PMID 41702225): "In this study, we present HTZ@D, a biocompatible, biodegradable, and electro-responsive hydrogel composed of hyaluronic acid, tannic acid, and zinc ions (Zn2+) loaded with doxorubicin (DOX)."
• NEWJul Cyclomatrix polyphosphazene-based crosslinked polyprodrug nanoparticles as carrier-free HCPT and DOX co-delivery system for tumor combination chemotherapy. (Colloids and surfaces. B, Biointerfaces, 2026, PMID 41812512): "Here, 10-hydroxycamptothecin (HCPT) was used as a short rigid linker to adjust the hyper-crosslinked structure of the classic HCCP-DOX nanomedicine, maintaining a high total drug content for HCPT and DOX co-delivery with desired acid-triggered release."
• NEWFeb Intelligent responsive DNA nanoflowers for combined chemo-gene-photothermal therapy of cancer. (Colloids and surfaces. B, Biointerfaces, 2026, PMID 41763115): "Subsequently, by loading doxorubicin (DOX), coating with metal-polyphenol networks (MPN), and functionalizing with hyaluronic acid (HA), a multimodal therapeutic nanoplatform (DNF@DOX@MPN@HA, FDMH) was constructed."
• NEWJul Manganese-mineralized boric acid-modified bovine serum albumin loaded on metal-organic frameworks as a pH- and GSH-responsive nanozyme for active targeted drug delivery. (Biomaterials advances, 2026, PMID 41875608): "The nanozyme PBM@ZIF-8 showed notable glutathione peroxidase-like and peroxidase-like activities, with high loading capacity of 10.34% with doxorubicin (DOX) and achieved pH- and glutathione (GSH)-responsive release, which is approximately three times the drug release amount in physiological conditions."
• NEWJun Exosomal MALAT1 expression associated with the cardioprotective effects of carvacrol in acute doxorubicin-induced cardiac injury: Potential involvement of Nrf2/Keap1-related signaling. (Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2026, PMID 42259137): "Doxorubicin remains an indispensable component of many chemotherapy regimens; however, its clinical use is limited by dose-dependent cardiotoxicity that may progress to dilated cardiomyopathy and heart failure."
• NEWJul Pulsed Electromagnetic Field Increases Doxorubicin-induced Mitotic Slippage in MDA-MB-231 Breast Cancer Cells. (Anticancer research, 2026, PMID 42373288): "Pulsed electromagnetic fields (PEMF) can be used to improve the efficacy of chemotherapeutic agents, such as doxorubicin (DOX)."
• NEWJul Anticancer Effects of Nortriptyline Hydrochloride in Osteosarcoma Cells Including Doxorubicin-resistant Cells. (Anticancer research, 2026, PMID 42373283): "Anticancer Effects of Nortriptyline Hydrochloride in Osteosarcoma Cells Including Doxorubicin-resistant Cells."
• NEWJul Doxorubicin as a Rescue Agent for Presumed Neoplastic Disease Causing Acute Intracavitary or Pulmonary Hemorrhage. (Journal of the American Animal Hospital Association, 2026, PMID 42379557): "Doxorubicin was used to treat 30 dogs presenting with acute onset of hemorrhage suspected to be caused by neoplastic disease, presumed hemangiosarcoma (HSAa), where surgical intervention was not possible."
• NEWMay Focused acoustic vortex-mediated targeted aggregation of engineered bacteria for in situ antibody production to enhance immunotherapy. (Acta biomaterialia, 2026, PMID 42217659): "The release of doxorubicin (DOX) and chlorin e6 (Ce6) induced immunogenic cell death, synergistically enhancing anti-tumor responses."