V₂C-Driven Nanodelivery Platform Potentiates Synergistic Breast Cancer Therapy

Abstract

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer. Conventional therapies for TNBC are limited by several drawbacks, including poor therapeutic efficacy and adverse effects. In contrast, photothermal therapy (PTT) has shown advantages in the treatment of TNBC due to its ease of administration and safe profile. Vanadium carbide (V 2 C), a new type of two-dimensional nanomaterial used in biomedicine, has shown excellent photothermal conversion and drug-carrying properties and has proven to be safe owing to its biodegradable characteristics. Therefore, in this study, the chemotherapeutic drug doxorubicin (Dox) was loaded onto V 2 C to prepare a new nanocomposite (V 2 C−Dox nanosheets). PTT with V 2 C−Dox induced localized therapeutic thermal effects and prompted drug release. V 2 C and V 2 C− Dox nanosheets alone were nontoxic to breast cancer cells. However, Dox, V 2 C +laser, and V 2 C−Dox+laser significantly inhibited the viability, clonogenic ability, and migration of breast cancer cells and induced their apoptosis, with V 2 C−Dox+laser having the strongest effect. In addition, combined transcriptomic and metabolomic analyses indicated that the amino acid biosynthesis pathway and the ferroptosis pathway resulting from the aberrant expression of SLC7A11, PED4D, and 2-oxo-4-hydroxy-4-carboxy-5-uronium imidazoline may be involved in the antibreast cancer effects of V 2 C−Dox after irradiation. Experiments in a breast cancer xenograft model showed that V 2 C−Dox@Gel significantly inhibited tumor growth following irradiation without inducing toxic side effects. Therefore, V 2 C−Dox@Gel, as a novel, controllable nanodelivery system for combined PTT and chemotherapy, could synergistically improve therapeutic efficacy in TNBC without causing adverse effects. Thus, it has immense potential as a therapeutic agent for TNBC.

Supramolecular “all-in-one” nanodrug based on perylene diimide for dual-mode imaging guided PTT-chemotherapy

“…9,16,17 Doxorubicin (DOX) hydrochloride, a first-line chemotherapeutic drug, is a water-soluble anthracycline antibiotic used for various solid tumors. 18 DOX exerts anti-proliferation effects via DNA intercalation, inhibition of topoisomerase II, and free radical generation. 19 Nevertheless, its efficiency is generally unsatisfactory, which may be ascribed to its serious side effects ( e.g.…”

l-Cysteine-Triggered Regulation of the Mitochondrial Energy Metabolism To Enhance Chemotherapy of Triple-Negative Breast Cancer

“…Triple negative breast cancer (TNBC) lacks related receptors and therefore poses a challenge for targeted therapy. − Currently, platinum-based drugs have become commonly used drugs for treating TNBC due to their broad-spectrum anticancer effects; however, their efficiency is heavily attenuated by cellular DNA repair mechanisms such as excision repair cross complementing-1 (ERCC1). , Therefore, small interfering RNAs (siRNA) and/or small-molecule inhibitors to downregulate ERCC1 nuclease have been used in combination with platinum drugs; , however, these are not widely applied in clinics, because of instability and off-target effects. Notably, DNA repair enzymes are adenosine triphosphate (ATP)-dependent multisubunit enzyme systems .…”

Precise Delivery of Ricin A-Chain and Photosensitizer by Aptamer-Functionalized Liposome for Targeted Chemo-Photodynamic Synergistic Therapy

“…The complexity, heterogeneity, and diversity of tumors seriously undermine the potential of cancer treatment. − Various available therapeutic drugs or treatment modalities are investigated to tackle pressing challenges facing the world. − Ricin, one of the protein toxin families, has presented great potential in cancer treatment. Ricin performed excellent therapeutic effect, as one molecule can enzymatically inactivating approximately 1500 ribosomes per minute, leading to rapid inhibition of protein synthesis and cell death. − Ricin consists of an enzymatic toxic domain, the A-chain (RTA), and covalently linked by a single disulfide bond to a slightly larger B chain (RTB), a lectin subunit that mediates cell entry. − After binding to the cell surface galactose residues through RTB, ricin is internalized into cells by endocytosis.…”