An energy-blocking nanoparticle decorated with anti-VEGF antibody to reverse chemotherapeutic drug resistance

Abstract

Multi-drug resistance (MDR) of tumor has greatly hindered the therapeutic effect of chemotherapeutic drugs, resulting in chemotherapy failure, and overexpression of ATP-binding cassette (ABC) transporters in cell membrane is the main cause of MDR.

Precise Photodynamic Therapy by Midkine Nanobody-Engineered Nanoparticles Remodels the Microenvironment of Pancreatic Ductal Adenocarcinoma and Potentiates the Immunotherapy

“…In the present study, we construct a novel tumor-targeting nanoplatform for PDAC imaging and PDT which integrates MDK nanobodies with PCP-NPs, enabling precise delivery of PCP-NPs to PDAC tissues enriched with dense fibrotic stromal components and extracellular matrix (ECM). Unlike targets highly expressed in tumor cells, MDK protein highly distributed in the TME is more likely to be accessible for targeted ligands such as small binder nanobodies, reminiscent of vascular endothelial growth factor A (VEGF-A) targeting strategies by which various nanomedicines have been modified with VEGF-A antibody such as Bevacizumab to realize tumor-specific targeting. − MDK-D4-Nb can effectively deliver PCP-NPs into MDK-positive PDAC tissues, accomplishing real-time tumor visualization by fluorescence imaging and PA imaging. Under light excitation, D4 Nb-PCP NPs can generate abundant ROS at the tumor sites and induce apoptosis and ICD through endoplasmic reticulum stress and mitochondrial dysfunction, leading to the tumor inhibition and activation of antitumor immunity (maturation of DC cells and increased infiltration of T cells) accompanied by the release of cytokines and reprogramming the immunosuppressive TME.…”

Quercetin, a Flavonoid with Great Pharmacological Capacity

“…At the same time, in a breast cancer xenograft model, significant increases in inhibitory effects and apoptotic cells were observed in a group treated with PEG-PLA-Qu compared with free quercetin at the same dose [ 118 ]. In this regard, Gu et al developed triphenylphosphine–quercetin/doxorubicin–PEG–monoclonal antibody (TQ/DOX-PEG-monoclonal antibody (mAb)) microcapsules to overcome multidrug resistance (MDR) by inducing mitochondrial damage and blocking ATP supply [ 131 ]. Triphenylphosphine quercetin conjugation effectively caused mitochondrial damage with ROS accumulation and depolarization of the mitochondrial membrane potential, leading to a significant decrease in ATP supply to ATP-binding cassette (ABC) transporters.…”

Quercetin, A Flavonoid With Great Pharmacological Capacity

“…At the same time, in a breast cancer xenograft model, significant increases in inhibitory effects and apoptotic cells were observed in a group treated with PEG-PLA-Qu compared with free quercetin at the same dose [118]. In this regard, Gu et al developed triphenylphosphinequercetin/doxorubicin-PEG-monoclonal antibody (TQ/DOX-PEG-monoclonal antibody (mAb)) microcapsules to overcome multidrug resistance (MDR) by inducing mitochondrial damage and blocking ATP supply [131]. Triphenylphosphine quercetin conjugation effectively caused mitochondrial damage with ROS accumulation and depolarization of the mitochondrial membrane potential, leading to a significant decrease in ATP supply to ATP-binding cassette (ABC) transporters.…”