New drug carrier reduces the side effects of chemotherapy

Simultaneous delivery of two drugs, light controlled release drugs, tumor targeting

New drug carrier reduces the side effects of chemotherapy

The team used gold nanoparticles to hybridize the organometallic framework in situ to obtain a nanocarrier capable of simultaneously delivering chemotherapeutic drugs and immunosensitizing drugs

◎Hong Hengfei, Du Yang, our reporter Jiang Yun

The combined application of chemotherapeutic drugs and indoleamine 2,3-dioxygenase (IDO) inhibitors can significantly activate the human body's anti-tumor immune response and improve the efficacy

The team of Professor Wang Weilin, Dean of the Second Affiliated Hospital of Zhejiang University School of Medicine and leader of the Department of Hepatobiliary and Pancreatic Surgery, and Professor Mao Zhengwei from the Department of Polymer Science of Zhejiang University, used gold nanoparticles to hybridize the organometallic framework in situ, thereby achieving simultaneous delivery of chemotherapy Nano-carriers for drugs and immunosensitizing drugs

"At the same time, we have also used a variety of chemical modifications to make the nanocarrier have the functions of light-controlled drug release and tumor targeting, which greatly improves the accuracy and effectiveness of the treatment of hepatobiliary and pancreatic tumors, and reduces the side effects of drugs

Combination therapy to treat tumors has certain side effects on the human body

Tumor immunotherapy is an emerging tumor treatment method in recent years

Due to the heterogeneity of tumors, after receiving immunotherapy, only a small proportion of patients will produce effective T cells to kill tumor cells in an immune response

"Tumor cell antigens can stimulate specific immune cells to activate, proliferate, and differentiate, and ultimately produce antibodies and effector T cells.

Chemotherapeutic drugs can increase the sensitivity of tumors to immunotherapy, induce strong and continuous immunogenic death of tumor cells, and enhance the effectiveness of immunotherapy

"Currently, IDO inhibitors have not been approved for marketing, but since 2015, clinical trials for their combined use with chemotherapeutic drugs have been initially carried out internationally.

Near-infrared light controlled targeted release of nanomedicine

"The team used gold nanoparticles to hybridize the organometallic framework in situ

In recent years, gold nanoparticles have been widely used in biosensing and medical detection due to the characteristics of surface plasmon resonance absorption

The research team got inspiration from this and tried to use the dimerization characteristics of the combination of drugs and gold nanoparticles to carry out research on the light-controlled release of drugs

"Light has very good controllability, but the use of light to control the release of drugs is rare in the past, and a technical problem needs to be solved first

After the research team irradiated the tumor site with near-infrared light, the nanomedicine enriched in the tumor site can be released responsively and specifically, which can significantly reduce the damage to normal cells

Prevent interference or remove "armed transformation" of transport carriers

In the study, gold nanoparticles acted as prodrug carriers and near-infrared responders

"Another problem is that the drug is easily bound by blood proteins in the body and cleared by macrophages

Fluorescence imaging shows that the anti-cancer drugs delivered in this way can be specifically swallowed by tumor cells.
Under the control of near-infrared light, only tumor cells can be specifically activated, and cells in normal tissues outside the illuminated area will not be Activate, so the side effects of the drug are greatly avoided
.

"During the treatment period, the weight of the mice injected with the nanomedicine was not significantly reduced, and no obvious symptoms of toxicity were detected
.
" Ding Yuan said that the follow-up team will also carry out long-term in-depth safety research
.

"At present, the new anti-tumor drugs developed using gold nanocarriers have completed small animal experiments to verify their effectiveness and safety.
The team is ready to further systematically evaluate its biological safety in large animals and lay the foundation for clinical research
.
" Wang Weilin said , The team is also working on methods for large-scale and stable production of nano-drugs, with a view to realizing the industrialization of drugs as soon as possible
.