Table 4 Nanomedicines targeting cuproptosis for breast cancer treatment
From: Cuproptosis: a promising new target for breast cancer therapy
Nanomaterials composition | Type | Cancer | Tested model | Effects OR Involved mechanism | Ref. |
|---|---|---|---|---|---|
Cu@cLAs | CDT | BC | MCF-7/R nude mice | Cu@cLAs were dissociated into LA and dihydrolipoic acid (DHLA), thereby releasing Cu2+ and Cu+ ions. This process facilitated the efficient elimination of cancer cells by delaying metabolic depletion and elevating the ROS levels within tumor cells. | [127] |
Cu-siMDR-CDDP | CDT | BC | MCF-7/CDDP cells | Upon release from Cu-siMDR-CDDP, CDDP initiates a cascade of bioreactions involving NADPH oxidase (NOX) and superoxide dismutase (SOD) in the acidic tumor microenvironment (TME), resulting in the production of H2O2. This H2O2 undergoes a Cu2+-catalyzed Fenton-like reaction, converting it into hydroxyl radicals (HO•) and causing a depletion of glutathione (GSH). This depletion disrupts the redox adaptation mechanism of drug-resistant cancer cells. Furthermore, HO•-induced lysosome destruction facilitates the delivery of MDR1 siRNA, which subsequently inhibits the expression of P-glycoprotein (P-gp) and reduces the efflux of CDDP. | |
NH2-MIL-101(Fe)/D-pen | CDT | BC | MCF-7 cells | The released d-pen chelated Cu, which is highly abundant in cancer environments, leads to the production of excess H2O2. This H2O2 is then decomposed by the Fe present in NH2-MIL-101(Fe), generating hydroxyl radicals •OH. Consequently, the cytotoxicity of NH2-MIL-101(Fe)/d-pen was observed in cancer cells. | [128] |
NH2-MIL-101(Fe)/CPT-11 | CDT | BC | MCF-7R-bearing BALB/c nude mice | Among all the tested formulations, the combined formulation demonstrated the most significant anticancer effects, attributed to the synergistic interaction between CDT and chemotherapy. | [128] |
Cu-Cys NPs | CDT | BC | MCF-7R-bearing NOD SCID mice | In situ glutathione-activated CDT, reinforced by H2O2, induces tumor cell apoptosis. Cu-Cys NPs effectively inhibited drug-resistant breast cancer in vivo without causing notable systemic toxicity. | [132] |
Hollow Cu9S8 NPs | CDT | BC | 4T1 tumor-bearing mice | Compared to solid Cu9S8 NPs, the increased number of active sites and enhanced photothermal performance result in enhanced CDT. | [156] |
Vk3 @MOF-199 | CDT | BC | 4T1 tumor-bearing mice | NQO1 catalyzes Vk3 to generate sufficient H2O2, which amplifies the effect of CDT. | [134] |
DOX@BSA-Cu | CDT | BC | 4T1 cells and MCF-7 cells | DOX enhances the H2O2 content and promotes the generation of hydroxyl radicals, thereby amplifying the effectiveness of CDT. | [157] |
mCMSN | CDT | BC | MCF-7tumor-bearing mice | Target-cell-specific GSH depletion enhances CDT, while simultaneously relieving hypoxia to improve PDT. | [133] |
Au-CuS YSNPs | CDT/PDT/PTT | BC | 4T1 tumor-bearing mice | Au-CuS YSNPs enhance the efficacy of PDT/PTT due to their localized surface plasmon resonance effect. | [155] |
FA-HMCu2-xS/BLM/LM | CDT/PDT/PTT/CT | BC | MCF-7 tumor-bearing mice | NIR-responsive drug release triggers further activation of BLM, leading to DNA cleavage. | [158] |
Dox@Cu-Met NPs | CDT/CT | BC | Breast-tumor-bearing mice | In the TME, dual-stimuli responsive drug release triggered by both pH and GSH levels mutually enhances the efficacy of CT and CDT. | [159] |
Cu3BiS3 NCs | PDT | BC | MCF-7 tumor xenograft-bearing mice | Cu3BiS3 nanocrystals achieve complete tumor regression using an ultra-low dose of NIR laser irradiation. | [148] |
BP-CuS-FA | PDT/PTT | BC | 4T1 tumor-bearing mice | A biocompatible and photodegradable CuS carrier enables a single laser-activated process for both PDT and PTT. | [160] |
CuxS/Au-PEG NPs | PTT | BC | EMT-6 tumor-bearing mice | Upon irradiation with a 1064 nm laser, the tumors experience an enhancement in their oxygenation status. Subsequently, the combination of photothermal therapy and radiotherapy yields remarkable synergistic therapeutic effects. This study introduces a novel concept for the design of a new-generation nanomedicine aimed at tumor thermoradiotherapy. | |
[(64)Cu]CuS NPs | PTT | BC | BT474 breast tumor | RT/PTT significantly delayed tumor growth in the subcutaneous BT474 breast cancer model and markedly extended the survival of mice harboring orthotopic 4T1 breast tumors. Furthermore, RT/PTT decreased the number of lung tumor nodules and inhibited the formation of tumor mammospheres from treated 4T1 tumors. | |
CuCo(O)/GOx@PCNs | PTT/IMT/ST | BC | 4T1 tumor-bearing mice | CuCo(O)/GOx@PCNs can achieve oxygen supply, glucose consumption, and photothermal ablation. Additionally, the immune response effect can further suppress tumor metastasis and recurrence. | |
MSN-DNA-CuS | PTT/CT | BC | HeLa and MCF-7 cells | Photothermal controllable and GSH-responsive drug release. | [161] |
CuPd TNP-1 | PTT | BC | 4T1;MCF7/MDR | The inhibition of autophagy through the use of 3-methyladenine or chloroquine exhibits a notable synergistic effect when combined with TNP-1-mediated PTT in triple-negative (4T1), drug-resistant (MCF7/MDR), and patient-derived breast cancer models. | |
Cyclodextrin DDC-Cu inclusion complexes | CT | BC | MDA-MB-231 cells | Cyclodextrin enhances the solubility of DDC-Cu while also increasing its toxic effect. | [152] |
DSF@PVP/Cu-HMPB | CT | BC | 4T1 tumor-bearing mice | TME-triggered release of Cu2+ facilitates the generation of the in situ anti-cancer complex CuL2, and NIR irradiation further enhances its anti-cancer activity. | [162] |