Anti-Pan-Rspo Chimeric Protein-Conjugated Albumin Nanoparticle Provides Promising Opportunities in Cancer Targeted Therapy

Rspos (R-spondins) belong to a family of secreted proteins that causes various cancers via interacting the corresponding receptors. However, targeted therapeutic approaches against Rspos are largely lacking. In this study, a chimeric protein Rspo-targeting anticancer chimeric protein (RTAC) is origi...

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Bibliographic Details
Published in:Advanced healthcare materials 2023-11, Vol.12 (29), p.e2301441-e2301441
Main Authors: Zheng, Shaoqin, Zhang, Xi, Pang, Zhongqiu, Liu, Jidong, Liu, Siyu, Sheng, Ren
Format: Article
Language:English
Subjects:
Albumin
Anticancer properties
Biocompatibility
Cancer
Cancer therapies
Cell surface
Drug delivery
Drug delivery systems
Endocytosis
Globular clusters
Nanoparticles
Proteins
Receptors
Serum albumin
Toxicity
Tumor cells
Tumors
Wnt protein
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Summary:Rspos (R-spondins) belong to a family of secreted proteins that causes various cancers via interacting the corresponding receptors. However, targeted therapeutic approaches against Rspos are largely lacking. In this study, a chimeric protein Rspo-targeting anticancer chimeric protein (RTAC) is originally designed, engineered, and characterized. RTAC shows satisfactory anticancer effects through inhibition of pan-Rspo-mediated Wnt/β-catenin signaling activation both in vitro and in vivo. Furthermore, a conceptually novel antitumor strategy distinct from traditional drug delivery systems that release drugs inside tumor cells is proposed. A special "firewall" nano-system is designed to enrich on tumor cell surface and cover the plasma membrane, rather than undergoing endocytosis, to block oncogenic Rspos from binding to receptors. Cyclic RGD (Arg-Gly-Asp) peptide-linked globular cluster serum albumin nanoparticles (SANP) are integrated as a vehicle for conjugating RTAC (SANP-RTAC/RGD) for tumor tissue targeting. These nanoparticles can adhere to the tumor cell surface and enable RTAC to locally capture free Rspos with high spatial efficiency and selectivity to antagonize cancer progression. Therefore, this approach offers a new nanomedical anticancer route and obtains the "dual-targeting" capability for effective tumor clearance and low potential toxicity. This study presents a proof-of-concept for anti-pan-Rspo therapy and a nanoparticle-integrated paradigm for targeted cancer treatment.
ISSN:2192-2640
2192-2659
DOI:10.1002/adhm.202301441