A Controlled-Release Nanocarrier with Extracellular pH Value Driven Tumor Targeting and Translocation for Drug Delivery

摘要

Over the past decades, nanoparticle-based drug-delivery systems (DDS) have received extensive attention in cancer therapy owing to their improved pharmacokinetics and pharmacodynamics arising from the enhanced permeation and retention (EPR) effect. To date, many passive targeting systems based on EPR, such as polymeric nanoparticles, liposomes, and mesoporous silica nanoparticles (MSNs), have been constructed to deliver drugs and improve their therapeutic effect. Although the passive targeting approaches can enhance the accumulation of drug in tumor tissue, they do have several limitations. In particular, the random diffusion of drugs in tumor tissue makes it difficult to control the process, possibly inducing multiple-drug resistance. In addition, the EPR effect is small, or non-existent, in certain tumors. To overcome these limitations, biomarker-targeting ligands, such as antibodies, aptamers, and peptides, have been used to further improve the passive targeting systems and concentrate drugs in cancer cells by actively targeting cancer cells after extravasation.7' However, many tumor biomark-ers are expressed in both cancer cells and healthy cells, leading to side effects in patients. Further, the strategy based on targeting a specific binding site is impeded by the heterogeneity of tumors, especially the differences among cells within a tumor. Therefore, it is important to explore a general feature of cancer physiology that will allow nano-particle targeting DDS, without relying on passive retention or on endogenous biomarkers.