Abstract
Designing an efficient nanocarrier to target multiple types of cancer remains a major challenge in the development of cancer nanomedicines. The majority of systemically administered nanoparticles (NPs) are rapidly cleared by the liver, resulting in poor tumor-targeting efficiency and severe side effects. Here, we present a delicately tailored design and synthesis of fluorescent bottle-brush polymers and screen nine derived NPs, each varying in size and surface coatings, for tumor imaging and targeted delivery. Our optimized polymer bearing (oligo(ethylene glycol) methyl ether methacrylate) in the side chains shows reduced macrophage uptake, prolonged blood-circulation time (up to 27 h), and exceptionally high accumulation in the tumor compared to the liver, elucidating an immune-evasion-induced tumor-targeting mechanism. High tumor accumulation significantly improved the antitumor efficacy. The outstanding tumor-targeting ability has been further validated across five distinct tumor models, including orthotopic glioblastoma and pancreatic cancer, which demonstrate the universality of our polymeric nanocarrier for tumor-targeting delivery.
Overview
- The study aims to design an efficient nanocarrier to target multiple types of cancer, specifically focusing on systemically administered nanoparticles (NPs) and their poor tumor-targeting efficiency and severe side effects. The study presents a delicately tailored design and synthesis of fluorescent bottle-brush polymers and screen nine derived NPs, each varying in size and surface coatings, for tumor imaging and targeted delivery. The primary objective is to optimize a polymer bearing (oligo(ethylene glycol) methyl ether methacrylate) in the side chains for tumor-targeting delivery and to validate its outstanding tumor-targeting ability across five distinct tumor models.
Comparative Analysis & Findings
- The study compares the outcomes observed under different experimental conditions or interventions, specifically focusing on the optimized polymer bearing (oligo(ethylene glycol) methyl ether methacrylate) in the side chains. The results show reduced macrophage uptake, prolonged blood-circulation time (up to 27 h), and exceptionally high accumulation in the tumor compared to the liver, elucidating an immune-evasion-induced tumor-targeting mechanism. The outstanding tumor-targeting ability has been further validated across five distinct tumor models, including orthotopic glioblastoma and pancreatic cancer, demonstrating the universality of the polymeric nanocarrier for tumor-targeting delivery.
Implications and Future Directions
- The study's findings have significant implications for the field of research or clinical practice, as they demonstrate the potential of a delicately tailored design and synthesis of fluorescent bottle-brush polymers for tumor-targeting delivery. The study identifies key limitations, such as the need for further optimization of the polymeric nanocarrier for specific tumor types and the need for long-term safety and efficacy studies. Future research directions could build on the results of the study, explore unresolved questions, or utilize novel approaches, such as the development of multifunctional nanocarriers for tumor imaging and targeted delivery.