Targeted Drug Delivery System Based on Copper Sulfide for Synergistic Near-Infrared Photothermal Therapy/Photodynamic Therapy/Chemotherapy of Triple Negative Breast Cancer

Abstract

Multi-modal synergistic therapy, especially the integration of near-infrared laser phototherapies and chemotherapy, is often sought after owing to its minimal invasiveness, low side effects, and improved anticancer therapeutic efficacy. Herein, CuS nanoparticles were first coated with zinc phthalocyanine derivant (Pc)-functionalized mesoporous silica (mSiO2-Pc) to achieve a drug delivery system (CuS@mSiO2-Pc) with photothermal/photodynamic therapy. Chemical drug DOX was subsequently loaded for chemotherapy, and hyaluronic acid (HA) was employed as a covering material with cancer targeting. The as-obtained CuS@mSiO2-Pc(DOX)@HA nanoparticles were nano-sized with good biocompatibility, effective DOX loading, and controllable DOX releasing. Expectedly, this multifunctional nanoplatform exhibits effective generation of reactive oxygen species and hyperthermia upon the near-infrared laser irradiation. Most importantly, the nanoparticles were targeted into 4T1 cells and showed significantly remarkable cytotoxicity under near-infrared laser irradiation, proving their synergistic therapeutic efficacy. Therefore, this targeted drug system based on CuS with synergistic photothermal therapy/photodynamic therapy/chemotherapy has great application prospects in clinical anticancer treatment for triple negative breast cancer.

Applications of Cu2+-Loaded Silica Nanoparticles to Photothermal Therapy and Tumor-Specific Fluorescence Imaging

“…CuO exhibits notably higher cytotoxicity compared to other metal oxides [11,12]. Although photothermal agents composed of CuS are recognized for their enhanced biocompatibility due to their biodegradability [13,14], they manifest low photothermal efficiency, necessitating intense laser power exceeding 14 W/cm 2 to achieve a sufficient photothermal effect [15]. Such elevated laser power has the potential to inflict damage even on normal cells [16].…”

Carrier-free chemo-phototherapeutic nanomedicines with endo/lysosomal escape function enhance the therapeutic effect of drug molecules in tumors

“…Numerous therapeutic combinations have been achieved in nanomedicines, where nanoparticles effectively encapsulate multiple components and deliver them concurrently to cancer cells. [3][4][5][6][7][8][9] In addition, nanocarriers aid in enhancing the pharmacokinetics and tumor accumulation of encapsulated drugs. 10 Clathrin-mediated endocytosis serves as the primary cellular uptake pathway for NPs (generally above 50 nm).…”

Iron-Doped Metal–Zinc-Centered Organic Framework Mesoporous Carbon Derivatives for Single-Wavelength NIR-Activated Photothermal/Photodynamic Synergistic Therapy

“…One part consists of photothermal agents such as gold nanostructures, 18 carbon nanomaterials, 19 and MoS 2 20 nanosheets that are then combined with photosensitizers through surface modification and encapsulation to achieve the purpose of combined therapy. 21 This inevitably causes them to be limited by the complex synthetic process and low assembly efficiency, thereby affecting the combined therapeutic effect. Therefore, it is urgent to find a photosensitizer with a simple synthesis process, which could directly produce reactive oxygen species and a strong photothermal conversion capability under the same visible or near-infrared (NIR) laser trigger.…”

“…But most of them are composed of two parts. One part consists of photothermal agents such as gold nanostructures, carbon nanomaterials, and MoS 2 nanosheets that are then combined with photosensitizers through surface modification and encapsulation to achieve the purpose of combined therapy . This inevitably causes them to be limited by the complex synthetic process and low assembly efficiency, thereby affecting the combined therapeutic effect.…”