Structure-inherent near-infrared bilayer nanovesicles for use as photoacoustic image-guided chemo-thermotherapy

Image-guided therapy, combined with imaging and therapeutic action, forms an attractive system because it can induce outstanding effects at focused locations. However, the conventional liposomes-based system cannot figure in therapeutic or imaging roles themselves, thereby causing the disadvantage of their biological unavailability as a theragnosis tool. Herein, the structure-inherent near-infrared bilayer nanovesicles are fabricated with amphiphilic heptamethine cyanine dye, PEG conjugated heptamethine cyanine dye, and gemcitabine (NEPCG) is developed for the novel photoacoustic image-guided chemo-thermotherapy system. The organic structure-inherent near-infrared bilayer nanovesicles are self-assembled and exhibit a liposome-like bilayer structure. Furthermore, NEPCG showed the high photoacoustic signal (PA) due to the specific accumulation in the tumor site. Delivered NEPCG than displayed concurrent chemotherapy and photothermal therapy (PTT) effects against cancer, triggered by PA imaging with minimal side effects. In vitro and in vivo experiments show that NEPCG can be used as outstanding contrast agents and completely obliterate the tumor without reoccurrence under laser irradiation. Therefore, this work presents the potential for the realization of unprecedented structure-inherent near-infrared bilayer nanovesicles as highly accurate and effective theragnostic tools in clinical fields.11Nsciescopu

Effective Combination Immunotherapy through Vessel Normalization Using a Cancer-Targeting Antiangiogenic Peptide–Antibody Hybrid

© 2022 Wiley-VCH GmbH.Although cancer immunotherapy using immune checkpoint blockade (ICB) has changed the paradigm for treating patients with certain cancers, its therapeutic benefits are limited to approximately one-fourth of patients, highlighting the potential for combining immunotherapy with another therapeutic modality. Here, a treatment regimen that combines a cancer-targeting antiangiogenic agent that inhibits angiogenesis within the tumor and ICB to improve therapeutic outcome is reported. The cancer-targeting antiangiogenic modality is constructed as a hybrid complex, designated HyPEPEDB-VEGF, comprising a cotinine-labeled bispecific peptide targeting both extra domain B of fibronectin (EDB) and vascular endothelial growth factor (VEGF) and an anticotinine antibody (Abcot). The resulting HyPEPEDB-VEGF specifically bound to EDB-overexpressing CT26 murine colorectal cancer cells and inhibited VEGF-induced proliferation of human umbilical vascular endothelial cells. Upon intraperitoneal injection, HyPEPEDB-VEGF preferentially accumulates in CT26 syngeneic tumors and inhibits tumor growth in a dose-dependent manner. Furthermore, the combination of HyPEPEDB-VEGF with an anti-PD-1 antibody (αPD-1) in conjunction with dose optimization of the two modalities leads to substantial inhibition of tumor growth without loss of body weight due to vascular normalization within the tumor. These findings suggest that the combination of cancer-specific antiangiogenic therapy using HyPEPEDB-VEGF together with ICB may be a feasible approach for effective cancer therapy.N