Chinese scholars have made new progress in the research of highly effective anti-tumor nanomedicine

With funding from the National Natural Science Foundation of China (approval number: 51833008), the team of Professor Shen Youqing of Zhejiang University has once again made new progress in the research field of active transcytosis-type highly effective anti-tumor nano-drugs
.

Following the previously proposed new mechanism for active tumor penetration of enzyme-responsive nanomedicine (Nature Nanotechnology, http:// , The team further proposed a strategy to simplify the structure of drug carriers: that is, using polymers that can weakly adhere to cell membranes but not proteins as carriers, so that they have long blood circulation properties and can trigger tumor cells without enzymatic reactions.
The characteristics of active transcytosis

In recent years, significant progress has been made in the clinical application of nanomedicine.
Some of these nanomedicines have been used clinically or are in clinical trials, but almost all nanomedicines have failed to achieve the expected clinical efficacy
.

This is because the EPR effect of clinical tumors is weak and highly heterogeneous, which makes it difficult for nanomedicine to enter tumor tissue from blood vessels; and the inherent larger size of nanomedicine (relative to small molecule drugs) and the compactness of tumor tissue, It is difficult for nanomedicine to penetrate into solid tumors, and it is impossible to deliver the drug to cells far away from blood vessels to effectively exert the drug effect

The nanomedicine design strategy based on active transcytosis can cleverly use the high cell density in tumors, allowing vascular epithelial cells and tumor cells to "actively" deliver nanomedicines between cells, so that nanomedicine delivery does not depend on the EPR effect.
Going outside the blood vessel effectively avoids the obstacles and size limitations of the passive diffusion of nanoparticles by the tumor microenvironment, and breaks the bottleneck of difficult extravasation and infiltration in the process of nano-drug delivery
.

The active transcytosis nano drug delivery system previously designed by the team requires an enzyme-catalyzed reaction to produce amines at the tumor site to trigger the active transcytosis of tumor cells.

In this study, the researchers designed and synthesized a zwitterionic polymer OPDEA containing a tertiary amine nitroxide structure, which has the characteristic of not adsorbing proteins but reversibly adsorbing to the cell membrane, so it can be "concealed" in the blood circulation system To achieve long circulation and tumor enrichment; on the other hand, it can be quickly taken up by tumor vascular endothelial cells and tumor cells, thereby triggering active transcytosis and achieving efficient tumor vascular extravasation and tumor penetration
.

Based on this, the researchers used OPDEA to carry the chemotherapeutic drug 7-ethyl-10-hydroxycamptothecin (SN38) to prepare a tumor active permeable nanometer with OPDEA as a hydrophilic outer layer and SN38 prodrug polymer as a hydrophobic core.

Therefore, OPDEA and its nano-drugs have the characteristics of not adsorbing to proteins but reversibly adsorbing to cell membranes, realizing long blood circulation, high-efficiency tumor vascular extravasation and high-efficiency intratumoral penetration that do not rely on traditional EPR effects, and the treatment is highly efficient and structural Simple, it provides a new idea for the design of clinically transformed nanomedicine