A near-infrared activatable biomimetic nanogel drug delivery system ARNGs@TMZ/ICG

The collaborative team of Professor Luo Liang from the School of Life Science and Technology of Huazhong University of Science and Technology, Professor Shi Bingyang and Professor Zou Yan from the College of Life Sciences, Henan University, have made the latest progress
in the research of in situ glioblastoma inhibition based on near-infrared activatable biomimetic nanogel carriers 。 The findings were published online in Nature Communications on November 11 in a research paper titled "Near infrared-activatable biomimetic nanogels enabling deep tumor drug penetration inhibit orthotopic glioblastoma.
"
。

Glioblastoma multiforme (GBM) is the most common primary tumor of the central nervous system, accounting for approximately 40%
of the total incidence of intracranial malignancies.
Although there are multiple methods such as surgical resection, radiation therapy, chemotherapy and so on for the treatment
of GBM.
However, due to insufficient blood circulation of drugs, limited penetration of the blood-brain barrier (BBB) and low drug intake for deep tumors, the treatment effect of patients was much lower than expected, and the median survival was only 12 months
。 In response to the above problems, the research team prepared a near-infrared activatable nanogel system by crosslinking pullulan sugar and oxidically degradable polydiyne derivative PDDA, loaded the FDA-approved near-infrared (NIR) photosensitizer indocyanide green (ICG) and the first-line chemotherapy drug temozolomide (TMZ) for the treatment of GBM into the nanogel, and biomimetically coated with apolipoprotein E (ApoE)-modified red blood cell membrane biomimetic, and developed a near-infrared activatable biomimetic nanogel delivery system ARNGs@TMZ/ ICG
。

Compared with other photoresponsive drug delivery systems, PDDA-based nanogels can be efficiently and rapidly activated under near-infrared illumination conditions, and have certain stability under biological endogenous conditions, which is of great significance
for improving their stability in the circulatory system and avoiding drug leakage that may occur in non-tumor microenvironments.
It was found that near-infrared light irradiation of ICG produces reactive oxygen species (ROS), which triggers the degradation of PDDA skeleton, and the mechanical properties of the entire nanocarrier become softer, triggering the efficient release of local drugs and facilitating the penetration
of drugs into deep tumor tissues.
Therefore, this activation process is particularly beneficial for maintaining higher concentrations of TMZ and ICG
in deep GBM lesions.

Near-infrared efficient activation of nanocarriers based on PDDA

After intravenous administration, the ARNGs@TMZ/ICG nanodrug carrier system utilizes surface-targeted molecules for efficient enrichment in glioma tissue
.
Reactive oxygen ROS generated by near-infrared radiation ICG subsequently precisely activated the ARNGs@TMZ/ICG
at the tumor site.
Modification of the ApoE functionalized red blood cell membrane further prolongs cycle time, improves tumor aggregation, and promotes blood-brain barrier penetration
of nanogels.
When the nanogel has achieved effective tumor aggregation, the nanocarrier
can be activated by near-infrared illumination at the right time by ICG fluorescence tracing.
Based on the above design strategies, this biomimetic nanogel showed high anti-GBM efficacy in both in situ U87 MG and GBM stem cell (CSC2) tumor models, with good biocompatibility, low toxic side effects, and nearly three
times higher median survival time.
Thus, ARNGs@TMZ/ICG inhibits in situ GBM
more effectively than similar responsive nanosystems targeting ligand modification.
Overall, this study shows that PDDA-based NIR activatable nanogels not only have advantages as a potential therapeutic platform for the treatment of malignant glioblastoma, but also pave the way
for the design of precise and controllable nanocarriers to achieve efficient treatment of tumors in situ.

Zhang Dongya, a doctoral student from the School of Life Sciences, Henan University, and Dr.
Tian Sidan, School of Life Science and Technology, Huazhong University of Science and Technology, are co-first authors of the paper, and Professor Luo Liang, School of Life Science and Technology, Huazhong University of Science and Technology, Professor Bing Yang and Professor Zou Yan, School of Life Sciences, Henan University, are co-corresponding authors
of the paper.
Professor Yang Xiangliang, School of Life Sciences, Huazhong University of Science and Technology, Professor Zheng Meng, College of Life Sciences, Henan University, and Professor Jong Bae Park from the Organ Cancer Division of the National Cancer Center Research Institute of Korea provided important guidance and assistance
for the research work of this paper.
This work was supported
by the National Key Research and Development Program of China, the National Natural Science Foundation of China, and the Science and Technology Innovation Talent Program of Henan Province.

Link to the paper: