AsianScientist (May 27, 2015) – The drugs arrived in a bright green storage bag. Mike sat back in his chair, arm outstretched and resigned himself as a nurse loaded bottles of colorful poisons, one by one, into his drip. A fluorescent yellow sticker read “WARNING: CYTOTOXIC,” an uncomfortable reminder of what he was in for.
Despite much hype and talk of “magic bullets” and billion dollar drugs, the majority of cancer treatments available today involve no shortage of collateral damage. Nausea, night sweats, rashes, ulcers, sores, hair loss; as their 20+ page side-effect booklets demonstrate, cancer-busting drugs can have some gruesome effects on the body.
A brief look at how they work reveals why: most chemotherapies target dividing cells, a category which fits nicely with the remit of cancer—defined as uncontrolled cell division— but also includes cells in our bone marrow, digestive system and hair follicles.
In essence, it’s a race: the aim is to destroy the enemy before you kill yourself. Chemotherapy is like fighting a guerrilla war, with targets hiding among innocent bystanders. You don’t need to be a military strategist to know that carpet bombing is flawed.
In fact, the challenge is colossal and not unique to cancer therapy. Medicines for a multiplicity of diseases, including antibiotics and drugs for cardiovascular disease, epilepsy and multiple sclerosis, are potent toxins, even at low doses. In terms of drug development, we may be losing out on thousands of effective medicines every year. 40 percent of promising new candidates fail pre-clinical trials in animals because of toxicity, a phenomenon which hikes discovery and development costs of a new pharmaceutical drug to more than US$1 billion for every medicine that makes it to the pharmacy. Surely there’s another way?
Old drugs, new packaging
As it happens, there is and it doesn’t involve newer drugs. In the past decade scientists have focused on engineering “nano-carriers” to help with drug delivery. Nano-scale devices (nano meaning dwarf in Greek), which are measured in billionths of a meter—100 nanoparticles placed in a row is approximately the width of human hair—can be used to protect, target and deploy payloads of medicine in the human body. Futuristic? Very. Practical? Only time will tell. There is certainly no shortage of enthusiasm for the technology among scientists, who have set to work imagining up a kaleidoscopic array of nano innovations, including DNA origami, quantum dots, rockets, balloons, burrs, bullets, bubbles and bots.
If the battle against cancer is war, the latest wartime technology is needed. What we need now are drones that lock onto their target and anti-radar stealth technology.
Hitting the bull’s-eye
One champion of our nano-future is Professor Zhang Liangfang of the Department of Nanoengineering at the University of California, San Diego. His team is developing lipid capsules, which function like artificial cell membranes, as drug carriers. The capsules are studded with polyethylene glycol (PEG), a synthetic chemical found in shampoo, rocket fuel and toothpaste. In his system, a lipid-PEG shell surrounds the capsule to control drug release into the bloodstream and protect the drugs from being detected by the immune system.
Part of the problem with conventional drugs is that they operate under a complete lack of discretion, free to wash around the body until they happen to hit upon the cells they are aimed at. This means that to deliver a sufficient amount to the target tissue, doses must be high. A targeted approach requires less drugs but delivers more, meaning lower toxicity and more effective treatments. There are several ways to do this. RNA, DNA, peptides and antibodies that bind to a target can be used to coat the surface of nanoparticles, sort of like writing an address on an envelope. Alternatively, nanocarriers can be primed to release drugs under certain conditions, such as in the acidic environment of a tumor, for example, or guided using magnets.
In newer iterations of his technology, Zhang and his team have used “smart” nanoparticles coated with antibodies that release their cargo only when they bind to molecules on the surface of pancreatic cancer cells.
An invisibility cloak
Of course, what is really needed in a war are agents that can stealthily and selectively seek out and destroy the enemy. When it comes to camouflage, nothing works better than a coat of materials from your surroundings. With this in mind, Zhang’s team has pioneered the use of cell membranes to envelop nanoparticles for drug delivery. The membranes are made from disembowelled red blood cells or cancer cells, surrounding a soft core of ceramics and metals bound to a drug. The team hopes the system will mask the nanocarriers as “self,” preventing clearance by the immune system and allowing drugs to circulate for longer periods in the bloodstream.
“The current state-of-the-art is to hide nanoparticles from the immune system by coating them with stealthy materials such as a polymer layer. Instead of hiding, I am looking for an approach that camouflages these foreign nanomaterials from the body’s immune system,” Zhang told Asian Scientist Magazine.
From its humble beginnings, chemotherapy has come a long way. With the help of a menagerie of bizarre and futuristic nanotechnologies, we may be entering a drug development renaissance, in which the drugs are no longer worse than the disease. Lower doses of medicines will be a boon for patients and cost savings will reduce the burden of disease on society.
This article was first published in the print version of Asian Scientist Magazine, Jul 2014.
To read more, subscribe to Asian Scientist Magazine in print and receive four issues of Asian Scientist Magazine delivered directly to your mailing address for 12 months, inclusive of taxes and postage.