Receiving numerous scam calls makes one more perceptive and averse to answering calls from unknown numbers. Likewise, cancer cells often develop resistance to current treatments such as chemotherapy, rendering them less responsive over time.
“As these resistant cancer cells are hard to kill, they often require higher amounts or multiple drugs to treat, which can cause severe side effects,” said Yi Yan Yang, Institute Scientist at A*STAR’s Bioprocessing Technology Institute (BTI).
Additionally, hurdles such as the poor solubility of drugs, their inability to sufficiently concentrate in tumours, rapid clearance from the body, and the unwanted side effects on healthy cells further complicate cancer drug development.
Yang’s team had previously developed guanidinium-functionalised biodegradable polycarbonates as promising anticancer agents capable of killing both drug-susceptible and drug-resistant cancer cells. They found that these macromolecules prevented cancer metastasis in mice without causing resistance. However, higher doses led to toxicity at the injection site due to the positively charged guanidinium groups.
In their follow-up study, the team turned to negatively charged carriers, which they hypothesised may form complexes with positively charged anticancer drugs to neutralise their charge, making them safer for patients while enhancing targeting to cancer cells.
Collaborating with researchers from A*STAR’s Bioinformatics Institute (BII) and Institute of Molecular and Cell Biology (IMCB), as well as the IBM Almaden Research Centre, USA, the team formulated next-generation nanocomplexes that were functionalised with carboxylic acid or benzoic acid. Next, they evaluated the impact of these treatments on the growth of both drug-susceptible and drug-resistant human breast cancer cell lines, as well as toxicity and efficacy in mouse models.
Yang and team discovered that the nanocomplexes significantly reduced the growth of both types of human breast cancer cells, including those resistant to drugs. By fine-tuning the formulation, the researchers also improved the longevity and safety profile of the treatment.
Impressively, they found that the treatments reduced tumour size in mice by 32 to 56 percent without harming vital organs like the liver and kidneys.
Yang said that the results highlight how nanocomplexes can offer a novel method for treating cancer by overcoming drug resistance, underscoring the critical role of drug delivery systems in enhancing treatment effectiveness and safety.
“Our anti-cancer polycarbonates may prevent or delay the development of cancer metastasis and drug resistance,” Yang remarked. To advance their approach from bench to bedside, the team is forging collaborations with partners in industry and academia to further develop their technology for clinical use.
The A*STAR-affiliated researchers contributing to this research are from the Bioprocessing Technology Institute (BTI), the Bioinformatics Institute (BII) and the Institute of Molecular and Cell Biology (IMCB).
