Nanotechnology in medicine.

Introduction

Spatially, human attention is focused on meter level and its fractions. It cannot entrain anything logarithmically beyond a certain range (kilometer on one end and millimeter on the other). However, matter, including biological matter, encompasses this range and beyond. Human red blood cells (RBC) are in the range of 10−6 m, protein molecule 10−9 m (nanometer), and atom 10−11 (quantum level), but the smallest spatial level that science and technology can fathom at the moment is Planck level, 10−35 m. The usual drug particle size is in the range of 10−4, which is around 10 times larger than RBC, and therefore, it is not surprising that majority of drug is wasted, not only decreasing its efficacy but also leading to its distribution to nontarget areas, increasing unwarranted side effects.

The philosophy of nanomedicine

Interestingly, among the components of biological cells, while carbohydrate is the energy currency, lipid is just the storage of energy, and it is the proteins that act not only as structural component but also prime mover of any change (enzyme action). Thus, if the drug particle size is reduced to nanorange (10−9 m), it becomes not only smaller than human cell but actually reaches the size of protein molecules, which are the final effectors in cell metabolism and messaging. Nanotechnology is the engineering of not only achieving this drug particle size but also carriers that deliver it to the “final executor,” the protein (in the cell) in a targeted manner. This way, not only efficacy will increase because each and every effector will be acted upon but also side effects will be minimized.

Principals of nanotechnology in cardiology

A number of important properties of these nanoparticles make them ideal as targeted delivery vehicles:

Increased adherence to damaged vasculature and endothelium.

Ability to noncovalently bind to carriers.

Potentiation of selective carrier uptake by cells or tissue.

Several biological agents like albumin/dextran/perfluorobutane gas microcarriers (PGMCs) nanoparticles can be utilized for cardiac applications. Albumin-coated gas microbubbles have an interesting property, that is, they do not adhere to normally functioning endothelium but can attach to dysfunctional endothelial cells or to extracellular matrix of the disrupted vascular wall, an interaction that could be used not only as a marker of endothelial damage but even drug delivery. The cardiovascular drugs can be incorporated into the microbubbles in a number of different ways, including binding of the drug to the microbubble shell and attachment of site-specific ligands. Perfluorocarbon as a component makes microbubbles sufficiently stable, so that they can circulate in the vasculature as blood pool agents, acting as a carrier of the drug until the site of interest is reached, in this case, damaged/dysfunctional vasculature. The mechanism of this selective adherence involves destruction of the negatively charged glycocalyx protecting the healthy endothelium and binding of microbubbles to activated leukocytes slowly rolling over the damaged endothelial surface.

Application in cardiology

Interventional cardiology

A number of therapeutic agents have been explored for incorporation into the PGMC-based delivery for preventing restenosis: sirolimus, paclitaxol, and antisense to c-myc (Fig. 1).

Fig. 1

Nanoparticle drug carrier.

Inflammation in cardiovascular tree

Vulnerable plaque (VP) rupture is the precursor to myocardial infarction. Increased inflammation at VP site has correlated with plaque rupture. New, targeted therapies are now available, which can pacify the local inflammation. Similar kind of therapy can be useful in context of acute coronary syndrome, peripheral vascular disease, or even atherosclerosis.

Future of nanotechnology in medicine

Nanodiagnostics

Medical diagnostics – Another application of this technology is construction of nanoelectronic devices that could detect the concentrations of biomolecules in real time for use as medical diagnostics.

Biological sensors/nanosensors – These are miniaturized nanoelectronic devices that could interact with single cells, undertake in vivo proteomic sensing, and could be used not only in basic biological research but also health monitoring.

Therapeutics

In the near future, it should become possible to construct machines (nanorobots) on the micrometer scale, made up of parts on the nanometer scale, like 100 nm manipulator arms, 10 nm sorting rotors for molecule-by-molecule reagent purification, and smooth superhard surfaces made of atomically flawless diamond (Fig. 2). These devices could be controlled by nanocomputers that would be able to activate, control, and deactivate these devices at will. Further, they would store and execute clinical plans, receive and process external signals and stimuli, communicate with other nanocomputers or external control and monitoring devices, and possess contextual knowledge to ensure safe functioning of the nanorobots. Some such likely devices are as follows:

Fig. 2

Structure of a nanorobot.

Nanoantibiotics – Nanotechnology is exploring various ways to control infection; gold, nanocrystalline silver, infrared, polymer-coated iron oxide, nitric oxide gas nanoparticles, quantum dots, and nanocapsules.

Nanorobotic microbivores – Artificial phagocytes called microbivores could patrol the bloodstream, seeking out and digesting unwanted pathogens, including bacteria, viruses, or fungi and converting them into inert material like harmless sugars or amino acids.

Nanosponges can absorb toxins and remove them from the bloodstream. The nanosponges are polymer nanoparticles coated with a red blood cell membrane. The red blood cell membrane allows the nanosponges to travel freely in the bloodstream and attract the toxins.

Surgical nanorobotics – A nanorobotic device could be introduced into the human body either via a natural opening or surgically. It could act as a homing device, searching for pathology, diagnosing it, and even curing it by nanomanipulation, all the while coordinated by an onboard computer, maintaining contact with the supervising surgeon via coded ultrasound signals (Fig. 3). Femtolaser, a nanorobot, can act like a pair of nanoscissors and vaporize diseased tissue locally while leaving adjacent tissue unharmed. This surgery has already been performed on individual chromosomes.

Fig. 3

Surgical nanorobot.

Regenerative medicine

Programmable nanorobots could act by mechanically reversing atherosclerosis, enabling dynamic homeostasis, enhancing immune system, reworking and replacing the DNA sequences in cells, and battling gross cellular insults. Thus, they could actually be programmed to repair specific diseased cells, encompassing cell therapy and tissue engineering, but functioning akin to natural healing processes.

Nanogenerators

This is another exciting area and could be used to create a new class of self-powered implantable medical devices, sensors, and portable electronics, by converting mechanical energy from body movement, muscle stretching, or water flow into electricity, while already our bodies are converting chemical energy in glucose to mechanical energy for movement. This novel technology will convert mechanical energy generated by movement within the body into electrical energy to run the pacemakers or ICDs obviating the need for external battery, thus leading to permanent “self-powered medical devices” (Fig. 4).

Fig. 4

Nanogenerator.