Small tumour microparticle enhances drug delivery efficiency and therapeutic antitumour efficacy

Extracellular Vesicles
/References

Background Targeted delivery of chemotherapeutic drugs to tumour cells is a major challenge for cancer chemotherapy. Recent studies show that tumour cell-derived microparticles can be used as vectors to package chemotherapeutic drugs, and selectively deliver drugs to tumour cells. Nevertheless, since the particle size range of microparticles is relatively wide, the sizes may exhibit different pharmacokinetic characteristics in the body, which will have a great impact on the application of drug-loaded microparticles. Here in this report, we compare the characteristics, distribution in vivo and antitumour efficacy of small microparticles (SMPs, ≤ 200 nm) and large microparticles (LMPs, > 200 nm) which loaded with methotrexate, in order to screen out more suitable carrier sizes. Results In vivo and in vitro studies have proved that the drug-loaded vesicles of SMPs (mainly 100–200 nm) are more reasonable, and the drug content and maintenance in tumour tissues. The time is significantly higher than that of LMPs (mainly 400–500 nm). At the same time, we found that SMPs can be better taken up and processed by DC cells to promote the proliferation of specific T cells. SMPs show obvious advantages in both drug delivery and immune activation, which is verified by the comparison of the efficacy of SMPs and LMPs in the treatment of solid tumours in mice. Conclusions The present data demonstrate that the SMPs had a higher cumulative concentration in tumour tissue, and the tumour suppressive effect was also significantly better than that of LMPs. It provides important process parameters for the drug-loaded vesicle delivery system. Future works will aim to expand production scale and improve the separation and purification process of the microparticles. Although the research and application of drug-loaded vesicles derived from tumour cells is still in its infancy, it has broad prospects for tumour therapy.

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2023
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