A novel intracellular polymerisation-based “prodrug” system can reduce tumour growth and metastasis while leaving main organs unaffected.
In the treatment of cancer, surgical intervention, radiotherapy, and chemotherapy are conventional options available for patients. Although chemotherapy is highly efficient, it is not without its severe toxicity and side effects. Hence, it would be ideal to develop drugs that can specifically target and be activated in/on cancerous cells. Lately, many prodrugs have been developed and used in cancer treatment to reduce side effects and promote efficacy.
Prodrugs are chemically modified drug molecules that release active drugs upon chemical transformation either by metabolic processes or external stimuli. External stimuli like light and synthetic molecules have to be introduced to the biological system to facilitate the transformation. Such stimuli are highly controllable, allowing for precise spatial and temporal control over the site of action.
In this study, a team of scientists from the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences has developed a new method that uses light to induce intracellular control polymerisation to treat cancer.
Based on their previous studies, the team had investigated if it was possible to construct artificial polymers in living cells and discovered that intracellular polymerisation can alter the cell cycle, cytoskeleton structure, and cell motility.
In the present study, the scientists utilised the method of light-controlled photoinduced electron transfer-reversible addition-fragmentation chain-transfer (PET-RAFT) polymerisation as it provides greater control over the polymerisation process. With this method, they achieved polymer synthesis with predictable and controllable molecular weight and reduced molecular weight distribution, which improves the regularity of the polymer as well as the controllability and reproducibility of the intracellular polymerisation system.
The team also looked deeper into the application potential of the intracellular polymerisation system, screened a library of monomers for the purpose of tumour treatment, and innovated a precision tumour treatment system based on intracellular polymerisation. They then demonstrated that their system could reduce tumour growth and metastasis.
Concerned about side effects, the team verified the biosecurity of their novel intracellular polymerisation-based “prodrug” system, and observed that the body weight, haematological parameters, and histological characteristics of the main organs of the experimental animals remain unaffected by intracellular polymerisation or arbitrary component administration.
“We hope that the precision tumour treatment method based on intracellular polymerisation in our work will open a new era in polymer therapy for cancer treatment,” said Dr. Geng, lead author of the study. [APBN]
Source: Zhang et al. (2022). Controlled Intracellular Polymerization for Cancer Treatment. JACS Au.