Anti‐Pan‐Rspo Chimeric Protein‐Conjugated Albumin Nanoparticle Provides Promising Opportunities in Cancer Targeted Therapy
Anti‐Pan‐Rspo Chimeric Protein‐Conjugated Albumin Nanoparticle Provides Promising Opportunities in Cancer Targeted Therapy
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DOI：
10.1002/adhm.202301441
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发表时间：
2023-07
影响因子：
10
通讯作者：
Shaoqin Zheng;Xi Zhang;Zhongqiu Pang;Jidong Liu;Siyu Liu;Ren Sheng
中科院分区：
文献类型：
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作者：
Shaoqin Zheng;Xi Zhang;Zhongqiu Pang;Jidong Liu;Siyu Liu;Ren Sheng
Rspos （R - spondins）属于一个分泌蛋白家族，通过与相应受体的相互作用导致各种癌症。然而，针对Rspos的靶向治疗方法在很大程度上缺乏。在这项研究中，一种靶向Rspo的抗癌嵌合蛋白（RTAC）被设计、工程和表征。RTAC通过抑制pan - Rspo -介导的Wnt/β - catenin信号激活，在体外和体内均显示出令人满意的抗癌效果。此外，还提出了一种概念新颖的抗肿瘤策略，不同于传统的在肿瘤细胞内释放药物的药物传递系统。一种特殊的“防火墙”纳米系统被设计成在肿瘤细胞表面富集并覆盖质膜，而不是进行内吞作用，以阻止致癌的Rspos与受体结合。环RGD （Arg‐Gly‐Asp）肽链球状簇血清白蛋白纳米颗粒（SANP）被整合为结合RTAC （SANP‐RTAC/RGD）的载体，用于肿瘤组织靶向。这些纳米颗粒可以附着在肿瘤细胞表面，使RTAC能够以高空间效率和选择性局部捕获游离Rspos，以对抗癌症的进展。因此，该方法提供了一种新的纳米医学抗癌途径，并获得了有效清除肿瘤和低潜在毒性的“双靶向”能力。本研究提出了抗pan - Rspo治疗的概念验证和靶向癌症治疗的纳米颗粒集成范例。
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.