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TJU Develops Hydrogel for Postoperative Reconstruction Following Breast Cancer

Breast cancer is one of the most common malignant tumors among women. The global incidence rate has been increasing year by year, posing a serious health threat to women. The development of modern medicine has promoted the development of a variety of new treatments and drugs, and the mortality rate of breast cancer has decreased significantly. Surgical resection remains the most commonly used and thorough treatment method. However, the high recurrence rate and metastasis of postoperative breast cancer have still not been effectively solved, which has become the biggest difficulty and challenge in clinical treatment. Therefore, postoperative treatment of breast cancer should focus on controlling recurrence and reconstruction of breast tissue. 

An injectable autoradiographic supramolecular nanocomposite hydrogel was designed by Prof. Liu Wenguang of Tianjin University. His group’s strategy is to combine local recurrence therapy with postoperative soft tissue reconstruction in breast cancer. Through in vitro near-infrared light control and real-time Computed Tomography (CT) imaging tracking, an accurate postoperative integrated diagnosis and treatment system is realized. Compared to conventional treatments, the near-infrared light-guided injectable hydrothermal gel can be precisely implanted into the lesion site by non-invasive treatment, increasing the local temperature within a short time and releasing the drug in situ to kill the residual cancer cells, and the implanted hydrogel is similar to the soft tissue structure, and has similar physical properties. It can also be used as a soft tissue filling material for breast reconstruction. 

For the ideal postoperative breast augmentation using hydrogels, it is necessary to have the function of preventing the recurrence of breast cancer and rebuilding the breast tissue. The constructed hydrogel stent should have the following functions: 

1) Thermoresponsive injectability; 

2) Rapid gelling time to ensure rapid solidification in the body; 

3) Similar physical properties as breast tissue; 

4) Self-adaptability to temperature variation to fit the breast cavity; 

5) Physiological stability; 

6) In situ therapeutic efficacy. 

The team designed and synthesized poly (N-acryloylglycinamide) -polyacrylamide (PNAGA-PAAm) supramolecular nanocomposite hydrogels containing gold nanoparticles and doxorubicin hydrochloride. The physical cross-linking of PNAGA's double hydrogen bonds allows the gel to maintain a stable swelling state in the physiological water environment, while the hydrogen bond of PAAm regulates the injectability. The polydopamine-gold nanoparticle in the network can form a cross-linking point through the interaction between polydopamine and amide groups to ensure the nanoparticles are firmly bound to the network, and then the photothermal conversion of the nanoparticle is induced by the near infrared light irradiation. When the temperature of the gel is slightly higher than the body temperature and the gel-sol transition temperature is reached, the secondary deformation of the injection and the body can be reached to achieve accurate and personalized filling. When near-infrared light is withdrawn, the sol state rapidly changes to a gel state, completing the fill cure. After the filling is completed, the photo-thermal conversion of the gel can be controlled by remotely controlling the near-infrared light to achieve the controlled release of the drug, killing part of the residual tumor cells in situ after a breast cancer operation, controlling the recurrence of breast cancer and completing the reconstruction of breast tissue. It is worth mentioning that due to the excellent X-ray attenuation characteristics of gold nanoparticles, the gel can also be real-time developed in vivo by CT and real-time tracking of the gel during the filling process. The injectable autoradiographic nanocomposite hydrogel combines photothermal therapy, drug controlled release and soft tissue reconstruction to provide a new design and research idea for the postoperative treatment of breast cancer. 

Diagram 1 Schematic illustration of the fabrication of PDA-AuNPs and nanocomposite PNAmPDAAu hydrogel and their theranostic application as the filler of cancerous breast tissue. 

The results were published online on April 14, 2018 in the Journal of Advanced Functional Materials (Adv. Funct. Mater. 2018, 1801000). The first author of the paper was PhD. Wu Yuanzhang. In recent years, Prof. Liu Wenguang's research group has systematically studied hydrogen bonded supramolecular PNAGA hydrogels. The relevant papers are published in (Adv. Mater. 2015, 27, 3566-3571; Adv. Funct. Mater. 2018, 28 , 1706644; ACS Appl. Mater. Interfaces 2016, 8,8956-8966; ACS Biomater. Sci. Eng. 2017, 3, 1109-1118; Macromol. Rapid Commun. 2017, 38, 1600695; J. Mater. Chem. B 2017, 5, 5588-5596; Polymer 2017, 126, 1-8; Biomater. Sci. 2016, 4, 1673-1681 ). 

By: School of Materials Science and Engineering

Editors: Qin Mian and Keith Harrington