With recent advances in drug discovery research, many drug candidate compounds with high therapeutic efficacy have been developed. However, many of these compounds have characteristics that make them difficult to handle, such as low water solubility and large molecular weights. As a result, it is poorly absorbed into the body, making it difficult to obtain sufficient therapeutic effects. Additionally, the drug is distributed into normal tissues, resulting in severe side effects. Fortunately, research is actively underway to develop drug delivery systems (DDS) that effectively solubilize these compounds and efficiently deliver them to cancer tissues.
A research group led by Professor Takashi Qian of the Osaka Metropolitan University Graduate School of Agriculture took on the challenge of developing a DDS that specifically transports paclitaxel (PTX), an anticancer drug with a molecular weight of 854 and low water solubility, to cancer tissues. The researchers utilized lipocalin-type prostaglandin D synthase (L-PGDS) enzyme as a novel DDS carrier to efficiently transport PTX.
Docking simulations and solubility tests revealed that PTX primarily binds to the upper region of the L-PGDS β-barrel protein structure through hydrophobic interactions. Additionally, its solubility was improved approximately 3,600 times compared to when suspended in phosphate-buffered saline. Furthermore, the research team added a targeting peptide CRGDK that binds to the neuropilin-1 receptor expressed on the surface of cancer cells to the C-terminus of L-PGDS, creating L-PGDS-CRGDK for selective delivery to cancer tissues.
When the drug efficacy was evaluated using a mouse model transplanted with MDA-MB-231 breast cancer cells, the commercially available formulation showed antitumor effects during the administration period, but the efficacy diminished when administration was discontinued. In contrast, PTX/L-PGDS and PTX/L-PGDS-CRGDK maintained their antitumor effects even after discontinuation of administration, and PTX/L-PGDS-CRGDK showed the highest tumor suppressive effect.
This study demonstrated that L-PGDS can bind relatively large drugs with molecular weights up to approximately 850, and further revealed that the introduction of targeting peptides enables selective delivery of anticancer drugs to cancer cells. The newly developed DDS is expected to greatly contribute to the advancement of cancer treatment in the future as a new delivery strategy for poorly soluble anticancer drugs. ”
Takashi Inui, Professor, Graduate School of Agriculture, Osaka Metropolitan University
The survey results are ACS Omega.
sauce:
Osaka Metropolitan University
Reference magazines:
Furuta, K., others. (2026). A drug delivery system for the anticancer drug paclitaxel using lipocalin-type prostaglandin D synthase coupled to a tumor-targeting peptide. ACS Omega. DOI: 10.1021/acsomega.5c09324. https://pubs.acs.org/doi/10.1021/acsomega.5c09324
