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Tumor-targeted delivery of photothermal agent and controlled release of concomitant chemotherapeutic drug are two key factors for combined photothermal chemotherapy. Herein, we developed a pH/near-infrared (NIR) dual-triggered drug release nanoplatform based on hyaluronic acid (HA)-functionalized gold nanorods (GNRs) for actively targeted synergetic photothermal chemotherapy of breast cancer. Targeting folate (FA), dopamine, and adipic acid dihydrazide triconjugated HA was first synthesized and used to decorate GNRs via Au-catechol bonds, and then an anticarcinogen doxorubicin (DOX) was conjugated onto HA moieties via an acid-labile hydrazone linkage, resulting in multifunctional nanoparticles GNRs-HA-FA-DOX. The nanoparticles exhibited excellent stability and had a pH and NIR dual-responsive drug release behavior. In vitro studies showed that the nanoparticles could be efficiently internalized into breast cancer MCF-7 cells and kill them under NIR irradiation in a synergistic fashion via inducing cell apoptosis. Pharmacokinetics and biodistribution studies in tumor-bearing mice indicated that the nanoparticles had a long blood circulation with a half-life of 2.4 h and exhibited a high accumulation of 11.3% in tumor site. The tumors of mice treated with combined chemotherapy and photothermal therapy were completely suppressed without obvious systemic toxicity after 20 d of treatment. These results demonstrated a great potential of GNRs-HA-FA-DOX nanoparticles for targeted synergistic therapy of breast cancer.

Cuproptosis is a very newly recognized regulated cell death modality that is distinct from known death mechanisms and shows enormous prospect in cancer treatment. However, its efficacy is copper-dependent and restricted by strictly regulated copper metabolism. Herein, a novel copper/iron hybrid hollow amorphous metal organic framework (HaMOF) is developed as an oxidative stress amplifier and copper/iron metabolic disrupter for synergistic cuproptosis/ferroptosis/apoptosis anticancer therapy. The HaMOF is fabricated from Cu 2+ , 3,3′-dithiobis(propionohydrazide) and Fe 3+ via an unsaturated coordination-etching integration strategy, and then doxorubicin is loaded followed by surface decoration with hyaluronan. The obtained DOX@ Fe/CuTH exhibits tumor microenvironment-triggered catalytic therapeutic property, wherein it can amplify cellular oxidative stress by simultaneously boosting H 2 O 2 production and depleting glutathione. Moreover, it can cause mitochondrial dysfunction and downregulate the expressions of copper transporter ATP7A and iron transporter FPN 1, thereby leading to metabolic disorders and high retentions of copper/iron in cytoplasm for •OH generation. The overloaded Cu 2+ can cause lipoylated protein dihydrolipoamide S-acetyltransferase aggregation and lead to cellular cuproptosis. Collectively, both augmented oxidative stress and overloaded copper/iron induce potent ferroptosis, which synergizes with cuproptosis and DOX-mediated apoptosis to efficiently suppress tumor growth. This bimetallic hollow nanoplatform provides a new therapeutic modality paradigm to boost cuproptosis-related therapies.

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A new cellulose-based superabsorbent polymer, carboxymethyl cellulose-graft-poly(acrylic acid-co-acrylamide), was prepared by the free-radical grafting solution polymerization of acrylic acid (AA) and acrylamide (AM) monomers onto carboxymethyl cellulose (CMC) in the presence of N,N 0 -methylenebisacrylamide as a crosslinker with a redox couple of potassium persulfate and sodium metabisulfite as an initiator. The influences of reaction variables such as the initiator content, crosslinker content, bath temperature, molar ratio of AA to AM, and weight ratio of the monomers to CMC on the water absorbency of the carboxymethylcellulose-graft-poly(acrylic acid-co-acrylamide) copolymer were investigated. The copolymer's structures were characterized with Fourier transform infrared spectroscopy. The optimum reaction conditions were obtained as follows: the bath temperature was 508C; the molar ratio of AA to AM was 3 : 1; the mass ratio of the monomers to CMC was 4 : 1; and the weight percentages of the crosslinker and initiator with respect to the monomers were 0.75 and 1%, respectively. The maximum water absorbency of the optimized product was 920 g/ g for distilled water and 85 g/g for a 0.9 wt % aqueous NaCl solution. In addition, the superabsorbent possessed good water retention and salt resistance.