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Making the switch: Potent anticancer liposomal drugs
Novel nanocarrier-based delivery strategy for chemotherapeutics improves selective cancer accumulation of drugs and reduces potential side effects.

Dr. Steve Roffler and colleagues at the Institute of Biomedical Sciences, Academia Sinica, have announced a general chemical approach to actively load and stably retain potent anticancer drugs in nanoliposomes. The study was published in the academic journal Nature Communications.

A major bottleneck in the effective use of nanomedicines to treat cancer has been the difficulty to deliver sufficient amounts of potent anticancer agents to tumor cells; highly potent drugs tend to leak out of biocompatible nanocarriers before the nanomedicine accumulates in tumors. This greatly decreases the amount of drug delivered to cancer cells and causes systemic toxicity to the patient.

The team developed a chemical switch that can be converted between different physical states based on pH. The switch can be attached to cancer drugs to facilitate efficient drug loading into liposomes, which are nanometer-sized spherical vesicles. Importantly, the switch can spontaneously change to a form that stably retains the anticancer drugs inside the liposomes.

Dr Roffler said, “Previous studies show that in most cases, drugs leak out of liposomes before the nanomedicine can accumulate in tumors”. Attachment of the switch to potent anticancer drugs allowed creation of very stable nanoliposomes. The switch prevents drug leakage to minimize unwanted toxicity and maximize accumulation of potent anticancer drugs inside tumors.

Furthermore, a linker between the drug and the switch is activated after uptake of the liposomes into cancer cells to allow selective release of anticancer drug. Treatment of mice bearing human breast cancer tumors resulted in high tumor/blood ratios of cancer drug in tumors and produced complete cures of majority of mice without apparent toxicity.

These studies indicate that the switch offers new opportunities to create safe and effective nanomedicines for the treatment of cancer and other diseases. Current studies are focused on treating pancreatic cancers or metastatic colon cancer in mice models.

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