Scientists develop temp sensitive cancer drug delivery tech
The study, conducted by A*STAR in collaboration with IBM and Stanford University, utilised thermoresponsive, water-soluble block copolymers loaded with the medication Paclitaxel, then injected directly into the tumour.
To create the nanocarriers, the team adapted recent work into Functional cyclic carbonates derived from a well-known building block – 2,2-bis(methylol)propionic acid (bis-MPA).
The biodegradable monomers were chosen for their versatility and because they readily undergo ring opening polymerization (ROP).
However instead of attaching the functional group at the early stage of synthesis, researchers simplified the method so that it requires only a single functionalisation reaction and a simple purification step for the introduction of pendent functional groups.
The result – a temperature dependant drug release from the micelles.
Led by A*STAR’s Yiyan Yang and Jeremy Tan, the researchers wrote: “We aimed to develop versatile and accessible strategies to the synthesis of thermoresponsive biodegradable nanocarriers by using organocatalytic polymerization techniques and new monomer syntheses to facilitate the study and control of the properties of thermoresponsive polymers.
“This study showed synthetic advancement toward the design and preparation of biodegradable thermoresponsive polymers with extremely low CMC (critical micelle concentration) values for injectable drug delivery systems.”
Toxicity issues
In the paper, ‘Thermoresponsive nanostructured polycarbonate block copolymers as biodegradable therapeutic delivery carriers’, the investigators acknowledge the industry’s interest poly(N-isopropylacrylamide) (PNIPAAM), which shows a temperature-induced collapse at 32 °C.
However, the polymer is problematic because it is toxic and non-biodegradable.
Yang and Tan say the method, though in some ways similar to previous work into thermoresponsive polymers, is a turning point, because the therapy is largely non-toxic.
Yang wrote: “While the polymer was not cytotoxic, paclitaxel-loaded micelles killed HepG2 human liver carcinomacells more efficiently at the body temperature as compared to free paclitaxel and paclitaxel-loaded micelles at the temperature below the lower critical solution temperature (LCST).
“These micelles are ideally suited to deliver anti-cancer drugs to tumor tissues through local injection.”
