New way to cut down toxicity of cancer drugs

Kidney damage risk of existing method can now be avoided

Indian scientists have successfully used a series of chemical methods to convert a highly toxic cancer drug into a harmless molecular blob, which continues to be an effective medicine but, unlike its poisonous predecessor, does not damage the kidney.

The discovery may open up a new treatment avenue for cancer patients by robbing off the toxicity of drugs like cisplatin and carboplatin, used to treat a broad range of cancer including testicular, ovarian, cervical, bladder, lung and head and neck cancer.

Converting the anti-cancer drug into a nano-scale globule, researchers claim, is a far more effective strategy rather than using a separate nano-vehicle for carrying the drug to targeted areas in the body.

Most of the nano-particles in drug delivery use a technique called encapsulation in which nano-particles adsorbs the drugs physically and release it subsequently after reaching the tumour cells. “The drawback is low loading of drugs and uncontrolled drug release. Our strategy is based on chemical modification of cisplatin keeping its structure and activity relationship in mind.

“We developed self-assembled cisplatin nano-particle, which overcomes the challenges,” said Sudipta Basu, one of the team members currently working at the Indian Institute of Science Education and Research, Pune.

Commonly used in anti-cancer treatment, cisplatin (and also other platinum-based drugs like carboplatin) severely damages kidney due to its toxicity.

“We used chemical tricks to create a supra-molecular assembly of cisplatin — a kind of large molecular assembly at the nano-level — which can enter the tumour cells but is too big to enter kidney. So there is no kidney damage. Its going to be a new strategy for drug development as toxicity is reduced significantly,” R A Mashelkar, former director-general of the Council of Scientific and Industrial Research and a professor at the National Chemicals Laboratory in Pune, told Deccan Herald.

As the number of cancer cases is on the rise in developing countries, the World Health Organisation projected over 12 million cancer deaths worldwide from 2030 — up from 7.6 million in 2008. The projected doubling of cancer deaths has compelled scientists to look for better cancer cure strategies.

Reporting their discovery in the June 25 issue of Proceedings of National Academy of Sciences, the team comprising scientists from Harvard Medical School, NCL, Harvard School of Public Health, Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Cambridge, said the discovery could lead to next-generation platinum-based anti-cancer drugs.

The team conducted animal experiments in mice for breast and ovarian cancer, which showed significant reduction of tumor and almost negligible side effects. The drug was administered through intra-venous injection. “Realistically, it will take at least 4-5 years before we do any human trial,” said Basu.

Nano size drug

The cisplatin nano-blob size is around 120 nm in size, which is accumulated in the tumor by a mechanism called “enhanced permeability and retention effect” of the tumor or passive targeting. “Its far more efficient means of drug delivery,” said Mashelkar.