zinc(ii)-phthalocyanine-trisulfonic-acid and Breast-Neoplasms

Patients with primary and bone metastatic breast cancer have significantly reduced survival and life quality. Due to the poor drug delivery efficiency of anti-metastasis therapy and the limited response rate of immunotherapy for breast cancer, effective treatment remains a formidable challenge. In this work, engineered macrophages (Oxa(IV)@ZnPc@M) carrying nanomedicine containing oxaliplatin prodrug and photosensitizer are designed as near-infrared (NIR) light-activated drug vectors, aiming to achieve enhanced chemo/photo/immunotherapy of primary and bone metastatic tumors. Oxa(IV)@ZnPc@M exhibits an anti-tumor M1 phenotype polarization and can efficiently home to primary and bone metastatic tumors. Additionally, therapeutics inside Oxa(IV)@ZnPc@M undergo NIR triggered release, which can kill primary tumors via combined chemo-photodynamic therapy and induce immunogenic cell death simultaneously. Oxa(IV)@ZnPc@M combined with anti-PD-L1 can eliminate primary and bone metastatic tumors, activate tumor-specific antitumor immune response, and improve overall survival with limited systemic toxicity. Therefore, this all-in-one macrophage provides a treatment platform for effective therapy of primary and bone metastatic tumors.

Topics: Animals; Apoptosis; B7-H1 Antigen; Bone Neoplasms; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Drug Carriers; Drug Delivery Systems; Female; Humans; Immune Checkpoint Inhibitors; Immunogenic Cell Death; Immunologic Memory; Indoles; Infrared Rays; Macrophages; Nanomedicine; Organometallic Compounds; Oxaliplatin; Photochemotherapy; Photosensitizing Agents; Prodrugs

PTX and zinc (II) phthalocyanine (ZnPc) co-loaded FSP-PTX-ZnPc NPs were designed. The resulting multifunctional NPs were evaluated systematically in vitro and in vivo, and the mechanism of drug-resistance reversal was investigated.. The NPs enhanced drug uptake in MCF-7/PDR cells by increasing drug solubility and impairing P-glycoprotein efflux. Additionally, magnetic targeting and enhanced permeation and retention (EPR) effect enhanced drug accumulation in tumor, facilitating the chemotherapeutic and photodynamic therapy effects. Moreover, FSP-PTX-ZnPc NPs could penetrate the blood-brain barrier, a desirable trait for brain disease therapy.. The multifunctional FSP-PTX-ZnPc NPs are an effective tool for overcoming drug resistance in breast cancer.

Topics: Albumins; Blood-Brain Barrier; Breast Neoplasms; Drug Delivery Systems; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Ferric Compounds; Humans; Indoles; MCF-7 Cells; Metal Nanoparticles; Micelles; Organometallic Compounds; Paclitaxel; Silicon Dioxide; Theranostic Nanomedicine