Magnetic Resonance/Infrared Dual-Modal Imaging-Guided Synergistic Photothermal/Photodynamic Therapy Nanoplatform Based on Cu1.96S-Gd@FA for Precision Cancer Theranostics.

Developing new nanoplatforms for dynamically and quantitatively visualizing drug accumulation and targeting within tumors is crucial for precision cancer theranostic. However, achieving efficient tumor therapy via synergistic photothermal/photodynamic therapy (PTT/PDT) using a single excitation light source, remains a challenge. In this work, we designed Gd-surface functionalized copper sulfide nanoparticles that were modified with folic acid (FA) (Cu1.96S-Gd@FA) to overcome the above limitations and promote PTT/PDT therapeutics. Here, Cu1.96S-Gd nanoparticles were synthesized via a coprecipitation method. All samples exhibited high longitudinal relaxivity (up to 12.9 mM-1 s-1) and strong photothermal conversion efficiency (50.6%). Furthermore, the Gd ions promoted electron-hole segregation, inducing the Cu1.96S-Gd nanoparticles to generate more reactive oxygen species (ROS) than pure Cu1.96S nanoparticles. The Cu1.96S-Gd@FA enabled the targeting of folate receptor (FR) and promoted cellular uptake, consequently enhancing oncotherapy efficacy. Compared to non-targeted Cu1.96S-Gd, a higher signal enhancement for magnetic resonance (MR) imaging in vivo by Cu1.96S-Gd@FA was recorded. Given photothermal ability, the nanoparticles also could be visualized in infrared (IR) imaging. Furthermore, the nanoparticles exhibited biodegradation behavior and achieved good drug elimination performance via renal clearance. Our strategy, integrating Cu1.96S-Gd@FA nanoparticles, MR/IR dual-modal imaging, and PTT/PDT into one nanoplatform, demonstrated great potential for anti-breast cancer therapy by effectively targeting FR overexpressed breast cancer cells.

NIR-Driven Intracellular Photocatalytic O2 Evolution on Z-Scheme Ni3S2/Cu1.8S@HA for Hypoxic Tumor Therapy.

Hypoxia in a tumor microenvironment (TME) has inhibited the photodynamic therapy (PDT) efficacy. Here, Ni3S2/Cu1.8S nanoheterostructures were synthesized as a new photosensitizer, which also realizes the intracellular photocatalytic O2 evolution to relieve hypoxia in TME and enhance PDT as well. With the narrow band gap (below 1.5 eV), the near infrared (NIR) (808 nm) can stimulate their separation of the electron-hole. The novel Z-scheme nanoheterostructures, testified by experimental data and density functional theory (DFT) calculation, possess a higher redox ability, endowing the photoexited holes with sufficient potential to oxide H2O into O2, directly. Meanwhile, the photostimulated electrons can capture the dissolved O2 to form a toxic reactive oxygen species (ROS). Moreover, Ni3S2/Cu1.8S nanocomposites also possess the catalase-/peroxidase-like activity to convert the endogenous H2O2 into ·OH and O2, which not only cause chemodynamic therapy (CDT) but also alleviate hypoxia to assist the PDT as well. In addition, owing to the narrow band gap, they possess a high NIR harvest and great photothermal conversion efficiency (49.5%). It is noted that the nanocomposites also exhibit novel biodegradation and can be metabolized and eliminated via feces and urine within 2 weeks. The present single electrons in Ni/Cu ions induce the magnetic resonance imaging (MRI) ability for Ni3S2/Cu1.8S. To make sure that the cancer cells were specifically targeted, hyaluronic acid (HA) was grafted outside and Ni3S2/Cu1.8S@HA integrated photodynamic therapy (PDT), chemodynamic therapy (CDT), and photothermal therapy (PTT) to exhibit the great anticancer efficiency for hypoxic tumor elimination.