Targeted Delivery of PD‐L1‐Derived Phosphorylation‐Mimicking Peptides by Engineered Biomimetic Nanovesicles to Enhance Osteosarcoma Treatment

Abstract

Osteosarcoma is a rare malignant bone-originating tumor that usually occurs in young people. Programmed cell death 1 ligand 1 (PD-L1), an immune checkpoint protein, is highly expressed in osteosarcoma tissues. Several recent studies have indicated that the tumor-related role of PD-L1 in tumors, especially non-plasma membrane (NPM)-localized PD-L1, is not limited to immune regulation in osteosarcoma. Here, mass spectrometry analysis is combined with RNA-seq examination to identify the intracellular binding partners of PD-L1 and elucidate the underlying mechanism of its action. It is found that the NPM-localized PD-L1 interacted with Insulin-like growth factor binding protein-3 (IGFBP3) to promote osteosarcoma tumor growth by activating mTOR signaling. This interaction is enforced after phosphoglyceratekinase1 (PGK1)-mediated PD-L1 phosphorylation. Based on these findings, a phosphorylation-mimicking peptide is designed from PD-L1 and it is encapsulated with a Cyclic RGD (cRGD)-modified red blood cell membrane (RBCM) vesicle

A nanohybrid synthesized by polymeric assembling Au(I)-peptide precursor for anti-wrinkle function

“…There is no doubt that peptide-based nanostructures have increased exponentially over the past few decades, which is attributed to their bio-inspired properties. Biomimetic strategies have been widely used in various types of research, such as tumor therapy ( He et al, 2022 ; Peng et al, 2022 ; Wu et al, 2022 ), vaccination ( Peng et al, 2022 ) and wound dress ( Mirhaj et al, 2022 ). And it has been reported that nanocarriers with bionic cell membranes were an effective and safe delivery system for osteosarcoma therapy ( Huang and Kiick, 2022 ).…”

Engineered nanomaterials enhance drug delivery strategies for the treatment of osteosarcoma

“…However, treatment of OS is still quite limited ( Sergi, 2021 ). Current conventional treatments for malignancy are chemotherapy, radiation therapy, and surgical resection ( Wu et al, 2022a ). Surgery can only remove the local tumor, but cannot cure the metastasis ( Zhu et al, 2022 ).…”

“…With the development of nanomedicine, nanomaterials offer new opportunities to improve drug delivery and reduce their adverse effects ( Xia et al, 2022a ). Nanoexamples are widely used in the immunotherapy of tumors using their unique size, charge properties, and targeting properties ( Wu et al, 2022a ). The enhanced permeability retention (EPR) properties of tumor cells allow nanoparticles to remain in the tumor microenvironment for a long time ( Morales-Orue et al, 2019 ).…”