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Prof. Xiangliang Yang and Prof. Zifu Li on Accounts of Chemical Research: Rational design of nanotherapeutics based on five features principle for potent elimination of cancer stem cells

time:2022-01-26 13:15     number of views:

(Correspondent Qingyuan Deng) On Jan 26th 2022, Prof. Xiangliang Yang and Prof. Zifu Li from College of Life Science & Technology and National Engineering Research Center for Nanomedicine published a review entitled " Rational design of nanotherapeutics based on five features principle for potent elimination of cancer stem cells " in Accounts of Chemical Research , an internationally renowned journal of the American Chemical Society.

Cancer stem cells (CSCs), also known as tumor initiating cells or tumor repopulating cells, which compose only a small fraction of tumor, have received tremendous attention during the past two decades, as they are considered as the ringleader for initiation and progression of tumor, therapy resistance, metastasis, and recurrence in the clinics. Hence, eradicating CSCs is critical for successful cancer treatment. To that end, various CSC-targeting therapeutic agents have been pursued. However, these CSC-specific drugs are ineffective towards bulk cancer cells. Furthermore, these anti-CSC drugs are not only eradicating CSCs but also affecting conventional stem cells in normal organs or tissues. In recent years, due to the tumor targeting ability and multi-function of nanomedicine, the design of nano drug delivery systems (NDDS) that can simultaneously deliver drug to CSCs has attracted extensive attention from researchers.

At the 2012 Chinese Pharmaceutical Conference, Professor Xiangliang Yang 's team proposed the five basic features of efficient nanotherapeutics (five features principle), which consist of long circulation, tumor accumulation, deep penetration, cellular internalization, and drug release. The nanotherapeutics designed in this way have achieved superior anti-tumor effects and low side effects in animal experiments. Relevant researches have been published in top peer-reviewed journals such as Nano Letters (2018), Nature Biomedical Engineering (2019), Nature Communications (2019), and Nano Today (2021).

Based on the systematic work of our team, we were invited to summarize the "five features principle" of tumor-targeted nanotherapeutics for eliminating cancer stem cells at Accounts of Chemical Research. Based on this principle, this review summarizes several NDDSs we constructed, including nanogels with adaptive hydrophobicity, CSCs-derived microparticles with tailored softness, and tumor exosome sheathed porous silicon biomimetic nanoparticles, for targeted drug delivery to tumor. These NDDSs achieved excellent drug delivery efficiency not only to bulk cancer cells but more importantly to CSCs. Furthermore, commercialized nanomedicines, such as Doxil and Abraxane, can be endowed with five basic features by hyperbaric oxygen therapy and therefore achieve outstanding drug delivery efficiency, potent CSCs elimination, and satisfying therapeutic effect. This review demonstrates that intractable CSCs can be tackled with a material-based approach, highlights the critical role of five features principle in designing effective nanotherapeutics, and pinpoints the significance of drug delivery efficiency in eliminating CSCs and bulk cancer cells.

Figure 1. Rational design of nanotherapeutics based on five features principle for potent elimination of cancer stem cells

Ph.D. candidates Zhijie Zhang, Qingyuan Deng from College of Life Science & Technology are co-first authors of this review. Prof. Xiangliang Yang, Prof. Zifu Li from College of Life Science & Technology are the corresponding authors. This review is supported by grants from the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Scientific Research Foundation of HUST, the Program for HUST Academic Frontier Youth Team, and the HCP Program for HUST.

The paper link: https://pubs.acs.org/doi/full/10.1021/acs.accounts.1c00635