Cancer chemotherapy comes with a plethora of side effects, ranging from the relatively mild like hair loss to the potentially life-threatening like immunodeficiency. Powerful but non-specific, chemotherapy behaves like a cluster bomb than a sniper shot, resulting in collateral damage to healthy cells.
Drug carriers called polymeric multilayer capsules (PMCs) could be key to equipping chemotherapy with a laser focus, thereby improving its therapeutic efficacy and tolerability. However, PMCs have remained a non-starter for clinical use, due to the absence of three essential features which must all be combined in one: biodegradation to ensure safety, small size for efficient tissue penetration, and retention of low molecular weight water-soluble molecules, which allows a greater variety of drugs to be packaged in the capsule.
Now with the joint efforts by scientists at A*STAR’s Institute of Materials Research and Engineering (IMRE) and Institute of Molecular and Cell Biology (IMCB), a new form of PMC that unites all three features in one has been successfully produced. This work was led by Maria Antipina, a Scientist at IMRE, and Anna Brichkina, formerly from IMCB and currently at the Philipps University of Marburg, Germany. The new PMC, made of poly-L-arginine and dextran sulfate, is biodegradable, non-toxic and eight times smaller than earlier iterations.
The researchers found that their PMCs loaded with fluorescent dye were able to effectively penetrate both lung and liver tissues in mice. Furthermore, after injecting the novel PMCs in both healthy and tumor-bearing mice, the group detected significantly more tissue penetrance in cancerous lung tissue compared to healthy lung tissue. This suggests that the novel PMC can specifically target cancer tissue, thus preventing off-target effects seen with conventional chemotherapy.
“The diminished size allows for selective targeting of tumor sites with the PMCs through the enhanced permeability and retention effect,” explained Antipina.
Work is now underway to improve cancer treatment efficacy by targeting tumor cells and the tumor microenvironment with PMCs, she said. “Our future research aims to show a therapeutic effect of PMC-based drug formulations in vivo on a model of lung cancer.”
Given that the novel PMC preferentially targets lung macrophages and epithelial cells, these capsules could also be used to treat other types of lung diseases unrelated to cancer. “With the world fighting COVID-19, we are eager to develop the PMCs into a drug formulation to treat acute respiratory distress syndrome caused by the coronavirus,” said Antipina. “The capsules can also be considered for the delivery of a new vaccine against COVID-19.”
The A*STAR-affiliated researcher contributing to this research is from the Institute of Materials Research and Engineering (IMRE) and Institute of Molecular and Cell Biology (IMCB).