AbstractRspos (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.

More from our Archive

• DOI: 10.3390/pharmaceutics15071916 2023

  Artificial Intelligence in Pharmaceutical Technology and Drug Delivery Design

  Lalitkumar K. Vora, Amol D. Gholap, Keshava Jetha, Raghu Raj Singh Thakur, Hetvi K. Solanki, Vivek P. Chavda

• DOI: 10.3390/ph16070934 2023

  A Scoping Review and Meta-Analysis of Anti-CGRP Monoclonal Antibodies: Predicting Response

  Ja Bin Hong, Kristin Sophie Lange, Lucas Hendrik Overeem, Paul Triller, Bianca Raffaelli, Uwe Reuter

• DOI: 10.3390/molecules28135145 2023

  Cancer Nanomedicine: Emerging Strategies and Therapeutic Potentials

  Manman Xu, Xinpu Han, Hongtai Xiong, Yijie Gao, Bowen Xu, Guanghui Zhu, Jie Li

• DOI: 10.3390/md21070384 2023

  Algal Phycocolloids: Bioactivities and Pharmaceutical Applications

  Silvia Lomartire, Ana M. M. Gonçalves

• DOI: 10.1002/ardp.202300097 2023

  Novel promising benzoxazole/benzothiazole‐derived immunomodulatory agents: Design, synthesis, anticancer evaluation, and in silico ADMET analysis

  Hazem Elkady, Khaled El‐Adl, Helmy Sakr, Adel S. Abdelraheem, Sally I. Eissa, Mohamed Ayman El‐Zahabi

• DOI: 10.3390/molecules28135282 2023

  Anti-α-Glucosidase, SAR Analysis, and Mechanism Investigation of Indolo[1,2-b]isoquinoline Derivatives

  Mengyue Li, Lin Li, Li Lu, Xuetao Xu, Jinhui Hu, Jin-Bao Peng

• DOI: 10.3390/pharmaceutics15071906 2023

  Comparison of Bovine- and Porcine-Derived Decellularized Biomaterials: Promising Platforms for Tissue Engineering Applications

  Hussein M. El-Husseiny, Eman A. Mady, Masahiro Kaneda, Kazumi Shimada, Yasumoto Nakazawa, Tatsuya Usui, Mohamed Elbadawy, Yusuke Ishihara, Moeko Hirose, Yohei Kamei, Ahmed S. Doghish, Hesham A. El-Mahdy, Walaa A. El-Dakroury, Ryou Tanaka

• DOI: 10.1002/adhm.202301010 2023

  Clinical Translation of Extracellular Vesicles

  Aayushi Ghodasara, Aun Raza, Joy Wolfram, Carlos Salomon, Amirali Popat

• DOI: 10.3390/molecules28135186 2023

  Homogeneous Electrochemical Aptamer Sensor Based on Two-Dimensional Nanocomposite Probe and Nanochannel Modified Electrode for Sensitive Detection of Carcinoembryonic Antigen

  Zhengzheng Yan, Shiyue Zhang, Jiyang Liu, Jun Xing

• DOI: 10.3390/molecules28145407 2023

  Recent Developments and Applications of Microbial Levan, A Versatile Polysaccharide-Based Biopolymer

  Marta Domżał-Kędzia, Monika Ostrowska, Agnieszka Lewińska, Marcin Łukaszewicz