【Scientific Research News】Professor Li Zifu of the School of Life Sciences, Huazhong University of Science and Technology and Professor Sun Chaoyang of Tongji Hospital have made new progress in the direction of tumor targeted nanomedicine

On December 16, 2022, Professor Li Zifu, School of Life Sciences, Huazhong University of Science and Technology, National Engineering Research Center for Nanomedicine, and Professor Sun Chaoyang of Tongji Hospital co-published a title entitled "Acta Biomaterialia Codelivery of adavosertib and olaparib by tumor-targeting nanoparticles for augmented efficacy and reduced toxicity"
.

Ovarian cancer is a malignant tumor with the highest mortality rate of gynecological tumors, with about 75% of patients diagnosed as advanced, and the 5-year survival rate is only 30%-40%.

The emergence of poly(ADP-ribose) polymerase (PARP) inhibitors has provided new options
for the treatment of ovarian cancer.
Among them, olaparib has been approved by the U.
S.
Food and Drug Administration for the treatment of ovarian cancer patients, but its use is limited to patients
with BRCA mutations.
In previous basic studies, we found that the combined application of olaparib and WEE1 inhibitors (e.
g.
, adavosertib) can promote cell death by altering the progression of the cell cycle, and this effect is not affected by
BRCA status.
However, the combined use of these two drugs has obvious toxic side effects, and the body often cannot tolerate it
.

Figure 1: Construction of TPNP-Ada-Ola nanodrug carrier system and its mechanism of
action.

In response to the above problems, with the advantage of nanodrug delivery systems, in this work, we designed a tumor targeting peptide TMTP1-modified mesoporous polydopamine (MPDA)-based nano-delivery system (TPNPs) for targeted joint delivery of Adavosertib and Olaparib for the treatment of ovarian cancer
.
Adavosert and Olaparib can be efficiently loaded into MPDA nanoplatforms and show release behaviors
triggered by the tumor microenvironment.
The results showed that this tumor-targeted nanodrug delivery system could significantly reduce the toxic side effects
caused by co-administration while enhancing the synergistic therapy of Adavosertib and Olaparib.
This work provides a new idea
for targeted delivery of WEE1 inhibitors and PARP inhibitors in the treatment of ovarian cancer.

Wang Wei, a doctoral student at Tongji Hospital, and Xiong Yuxuan, a doctoral student from the School of Life Sciences, are the co-first authors of the paper, and Professor Sun Chaoyang of Tongji Hospital and Professor Li Zifu from the School of Life Sciences are the co-corresponding authors
of the paper.

Article link: https://doi.
org/10.
1016/j.
actbio.
2022.
12.
021