English
Nanodrugs that can aggregate in the tumor microenvironment (TME) have shown tremendous efficiency in improving therapeutic outcomes. The strategy of utilizing electrostatic interactions as a driving force to achieve intratumoral aggregation of nanomedicines has attracted widespread attention among various methods. However, the significant differences between two nanomedicines with different physicochemical properties prevent them from being transported synchronously in the bloodstream and have equal opportunities for uptake by tumors, which significantly impairs the beneficial effect of nanomedicine aggregation within tumors. We propose a new strategy to construct a pair of extremely similar nanomedicines, called "twin like nanomedicines (TLNs)", which have the same physicochemical properties, including the same morphology, size, and electrical neutrality, thus giving them the same blood circulation time and tumor entrance. The 1:1 TLN mixture (TLNs Mix) injected intravenously into a mouse model can effectively accumulate at the tumor site and then respond to tumor enrichment. In addition to enhancing tumor retention, the resulting micrometer sized aggregates also exhibit high echo intensity, which is crucial for ultrasound imaging and ultrasound triggered penetrative drug delivery. Due to its unique characteristics, TLNs Mix carrying sonosensitizers, immune adjuvants, and ultrasound contrast agents exhibit effective sonodynamic immunotherapy for low vascular liver cancer, demonstrating its enormous potential in the treatment of solid malignant tumors.
