Chondroitin sulfate-based nanoparticles for enhanced chemo-photodynamic therapy overcoming multidrug resistance and lung metastasis of breast cancer

• Published in: Carbohydrate polymers Vol. 254; p. 117459
• Main Authors: Shi, Xiaoqun, Yang, Xiaoye, Liu, Mengyao, Wang, Rujuan, Qiu, Na, Liu, Yuanxiu, Yang, Haotong, Ji, Jianbo, Zhai, Guangxi
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 15.02.2021
• Subjects: Animals; Anti-metastasis; Antineoplastic Agents - pharmacology; ATP Binding Cassette Transporter, Subfamily B, Member 1 - antagonists & inhibitors; ATP Binding Cassette Transporter, Subfamily B, Member 1 - genetics; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cell Proliferation - drug effects; Cell Proliferation - radiation effects; Chemo-photodynamic therapy; Chemosensitizer; Chondroitin sulfate; Chondroitin Sulfates - chemistry; Combined Modality Therapy; Doxorubicin - pharmacology; Drug Carriers; Drug Resistance, Neoplasm - drug effects; Drug Resistance, Neoplasm - genetics; Drug Resistance, Neoplasm - radiation effects; Female; Gene Expression; Humans; Infrared Rays - therapeutic use; Lasers; Lung Neoplasms - genetics; Lung Neoplasms - secondary; Lung Neoplasms - therapy; MCF-7 Cells; Multidrug resistance; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Paclitaxel - pharmacology; Photosensitizing Agents - pharmacology; Porphyrins - pharmacology; Quercetin - pharmacology; Reactive oxygen species; Reactive Oxygen Species - agonists; Reactive Oxygen Species - metabolism; Xenograft Model Antitumor Assays; Reactive oxygen species; Chondroitin sulfate; Chemosensitizer; Chemo-photodynamic therapy; Anti-metastasis; Multidrug resistance
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2020.117459

•Novel chondroitin sulfate-based nanoparticles (PTX/CQE NPs) were initially prepared.•PTX/CQE NPs could exert enhanced chemo-photodynamic therapy in vitro and in vivo.•PTX/CQE NPs exhibited in vivo MDR inhibition and anti-metastasis efficacy. As a major therapeutic approach for cancer treatment, the effectiveness of chemotherapy is challenged by multidrug resistance (MDR). Herein, we fabricated novel redox-responsive, chondroitin sulfate-based nanoparticles that could simultaneously deliver quercetin (chemosensitizer), chlorin e6 (photosensitizer) and paclitaxel (chemotherapeutic agent) to exert enhanced chemo-photodynamic therapy for overcoming MDR and lung metastasis of breast cancer. In vitro cell study showed that nanoparticles down-regulated the expression of P-glycolprotein (P-gp) on MCF-7/ADR cells and thereby improved the anticancer efficacy of PTX against MCF-7/ADR cells. Moreover, NIR laser irradiation could induce nanoparticles to generate cellular reactive oxygen species (ROS), leading to mitochondrial membrane potential loss, and meanwhile facilitating lysosomal escape of drugs. Importantly, the novel nanoplatform exhibited effective in vivo MDR inhibition and anti-metastasis efficacy through enhanced chemo-photodynamic therapy. Thus, the study suggested that the multifunctional nanoplatform had good application prospect for effective breast cancer therapy.