Active Delivery of VLPs Promotes Anti‐Tumor Activity in a Mouse Ovarian Tumor Model

Abstract

Virus‐like nanoparticles (VLPs) have been used as an attractive means in cancer immunotherapy because of their unique intrinsic immunostimulatory properties. However, for treating metastatic tumors in the peritoneal cavity, such as ovarian cancer, multiple injections of therapy are needed due to the large peritoneal space and fast excretion of therapy. Here, it is reported on the development of active VLP delivery vehicles for the treatment of peritoneal ovarian tumors using biocompatible Qβ VLPs‐loaded Mg‐based micromotors. The autonomous propulsion of such Qβ VLPs‐loaded Mg‐micromotors in the peritoneal fluid enables active delivery of intact immunostimulatory Qβ VLPs to the peritoneal space of ovarian tumor bearing mice, greatly enhancing the local distribution and retention of Qβ VLPs. Such improved distribution and longer retention time of Qβ in the peritoneal cavity leads to enhanced immunostimulation and therefore increased survival rate of tumor‐bearing mice compared to a passive Qβ treatment. For clinical translation, the active delivery of VLPs holds great promise for tumor immunotherapy toward the treatment of different types of primary and metastatic tumors in the peritoneal cavity.

Medical Micro/Nanorobots in Precision Medicine

“…Active delivery in the peritoneal space of ovarian tumors was achieved, and the local distribution and retention of Q virus improved versus passive treatment. [216] Despite challenges, such as the potential Figure 4. Micro/nanorobot based delivery of biologics and genes.…”

“…Reproduced with permission. [ 216 ] Copyright 2020, Wiley. d) Sperm driven microrobot for heparin delivery capable of going against the flow.…”

“…Active delivery in the peritoneal space of ovarian tumors was achieved, and the local distribution and retention of Q β virus improved versus passive treatment. [ 216 ] Despite challenges, such as the potential for generating systemic immunity that is still required to overcome using this vaccine, these platforms show the first steps of micro/nanorobots in the delivery of biologicals in vivo and great promise in clinical scenarios.…”

Research Progress of Micro/Nanomotors for Cancer Treatment

“…The self-driving of Mgmicromotor in the abdominal cavity improved the local distribution and retention of virus-like nanoparticles, and further enhanced immune stimulation, thereby increased the survival rate of tumor-bearing mice. [70] Recently, inspired by the in vivo endogenous reaction of catalase and active oxygen to decompose L-arginine into nitric oxide (NO) and L-citrulline, our group designed and prepared a kind of hyperbranched polyamide-L-arginine (HLA) nanomotors, which was propelled by NO bubble produced from L-arginine decomposition ( Figure 3B). In this self-propulsion system, the reactants and products were both harmless to the human body and even could be used as drugs.…”

“…The results of fluorescence imaging and fluorescence quantification after 24 h of injection showed that virus‐like nanoparticles released from micromotor was concentrated in the tumor and major organs in the abdominal cavity. The self‐driving of Mg‐micromotor in the abdominal cavity improved the local distribution and retention of virus‐like nanoparticles, and further enhanced immune stimulation, thereby increased the survival rate of tumor‐bearing mice [70] …”