Lecture 10: Nanodrug Design and Methods of Activation

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Presentation transcript:

Lecture 10: Nanodrug Design and Methods of Activation Contents: Nanodrug Design Methods of Activation Ideal Radiation X-Ray Activation Activation in the Optical Range of the Spectrum Microwave Activation Activation by Magnetic Fields and Ultrasound Waves RF Wave Activation Conclusions

Nanodrug Design Nanodrugs/nanoparticles, selectively delivered to the tumor site, can be activated by radiation for drug release, or nanoparticles themselves can be used as a drug by producing biological damage through thermal, mechanical ablations or charged particle emission. By nanodrug activation, we mean heating of nanoparticles, photoelectron emission, Compton scattering, explosion of nanoparticles, generation of shock waves, sound waves, mechanical waves of high pressure, nanobubble formations, and so on. All these phenomena eventually kill the cancer cells and the tumor.

Nanodrug Design (continued) Nanodrug design includes the physical properties like material, optical and thermal, and morphological properties (shape, size and structure) of nanoparticles, which depend on the methods of nanodrug activation. By methods of activation, we mean using different types of radiation for a total body scan to activate the nanoparticles and reach any place inside the body. For example: If activation is based on radiation in the optical range of the spectrum, the best candidates for nanodrug design are plasmonic nanoparticles of different shapes, sizes and structures made of noble metals like Au, Ag and Pt. Also, silica, glass and polymer nanoparticles can be used for the optical range of the spectrum activation because of their relatively high absorption in that range and the ability of silica shells to be tuned to the desired wavelength of radiation.

Nanodrug Design (continued) If we use a magnetic field for activation, then the nanoparticles must be made of magnetic materials like iron, nickel and cobalt, and their compounds covered by biocompatible surface layer. For the x-ray activation, the nanoparticles are composed of crystals like bismuth sulphide, coated with a soft-protected layer to minimize the interaction with human chemistry, and designed to effectively absorb x-rays. The gold nanoparticles also could be used for effective x-ray activation.

Ideal Radiation for Activation The radiation is characterized by a wide range of the electromagnetic spectrum, starting with the very short wavelengths of gamma and x-ray radiation, and ending with the very long wavelengths of radiofrequency (RF) radiation. The best radiation for nanoparticle activation would be one which has deep penetration into the human body, with power load high enough to activate the nanoparticles, but sufficiently lower than the threshold energy to make any biological damage by the radiation itself.

Methods of Activation X-Ray Activation X-Ray Activation. Short electromagnetic waves like x-rays have good penetration depth, 10-25 cm depending on the exposure dose in both soft and bone tissues, and they have high-energy photons, enough to activate the nanoparticles. The intravenously administrated nanoparticles into the body are selectively attached to the cancer cells. After a certain incubation time, depending on the size of nanoparticles, the x-rays can be applied for a total body scan by using a machine similar to a computed tomography (CT) scanner. The mass attenuation coefficient of soft tissue in the x-ray photon energies spectrum is three orders of magnitude less than the mass attenuation coefficient of gold in the same range of photon energies. This allows us to reduce the exposure rate to the level of diagnostic doses, just good enough to activate the nanoparticles without harming the patient.

Methods of Activation X-Ray Activation (continued) The therapeutic effect of the localized activation of the nanoparticles by x-ray radiation is achieved by emission of the charged particles from the surface of the nanoparticles in photoelectric events, Compton scattering events and thermionic emission, or heating the nanoparticles to the temperatures high-enough for cell ablation. The charged particles emitted from the surface of nanoparticles destroy the DNA of the cancer cells through direct and indirect actions. In direct action, the charged particles destroy the DNA directly. The indirect action means that the charged particles react with water contained in the cell medium, producing hydroxyl radicals which are toxic for DNA of cancer cells. X-ray would seem to be good for a total body scan to activate the nanoparticles inside the body.

Methods of Activation Activation in the Optical Range of the Spectrum Activation in the Optical Range of the Spectrum. The optical range of the spectrum includes short ultraviolet (UV) waves, visible light and infrared (IR) radiation. A spectrum range from 400 to 700 nm is called visible light. Different types of lasers are reliable sources of coherent radiation in the optical range. Today, lasers are covering the whole optical spectrum from short UV up to long IR radiation. However, the penetration depth for most lasers in soft tissue is small and limited by the absorption of water.

Methods of Activation Activation in the Optical Range of the Spectrum (continued) As can be seen from the diagram, only the Nd:YAG laser with wavelength 1.06 µm has the deepest penetration of about 10 mm, corresponding to the window of transparency of water. Because of low penetration depth, researchers in laser physics use optical fibers to deliver optical light directly to the tumor. A single-mode optical fiber has a diameter of about 1 mm and is able to deliver light of high energy, enough to ablate the tumor, to almost any place inside the body. Laser surgery is widely used in clinics nowadays. However, because we have to know the exact location of the tumor in advance in order to deliver light to the right place, laser technology is not a universal technique of activating nanoparticles inside the body, since tumor or cancer cells can hide anywhere in the body.

Methods of Activation Microwave Activation If we search for the ideal or best radiation outside the optical spectral range, the longer waves in the microwave range also have good penetration depth and high power load that easily reaches high ablation temperatures in the tumor. But the problem with microwaves is water, the main content of the cells. The water absorbs a lot of microwaves, and a total body scan with high-energy microwaves will “cook” the patient. Because of this, researchers have to use antennas placed inside the tumor to deliver a controlled amount of microwave energy to limited places at the tumor site only. This technology works well for ablating large tumors with given locations, but not as a universal tool for a total body scan that is able to reach cancer at any unknown place.

Methods of Activation Activation by Magnetic Fields and Ultrasound Waves Magnetic fields and ultrasound waves are also characterized by good penetration into the human body. For the magnetic field activation technique, the nanoparticles must be composed of magnetic materials like Fe, Ni and Co, or their oxides, covered by peptide coating that reduces toxicity and provides efficient absorption by tumor cells. However, both fields (magnetic and ultrasound) have low energy load, and because of this, the magnetic field and ultrasound waves are used mostly for diagnostic purposes.

Methods of Activation (continued) We have briefly analyzed short x-rays, the optical spectral range, microwaves, magnetic fields and ultrasound waves in the search for a universal tool for nanoparticles activation inside the body. Each method has benefits as well as limitations. For example, the x-ray radiation is a good candidate for a total body scan to activate the nanoparticles inside the body. However, x-rays are toxic to the body and can cause a secondary cancer via direct and indirect DNA destruction in normal cells. The laser and microwave technologies work well at limited, well-known locations of tumor sites, so that these methods cannot be considered as a universal tool for activation of nanoparticles. Magnetic and ultrasound waves can easily penetrate the body but are too weak to cause any biological damage or heat the nanoparticles to the ablation temperatures.

Methods of Activation RF Wave Activation Let us continue searching for the best radiation for nanoparticle activation at longer wavelengths of the electromagnetic spectrum, i.e., RF waves. The human body, consisting of 60% water, has negligible absorption of RF waves with penetration depth of 20-200 cm for 13.56 MHz wave frequency. The RF waves are week waves and do not make any biological damage themselves. A therapeutic effect of RF waves can be reached by combining the RF radiation with nanoparticles to destroy the cancer. This gives a great opportunity to activate/heat nanoparticles injected in the human body with RF waves for diagnosis and treatment of diseases at any place inside the body harmlessly.

Conclusions The use of nanoparticles can dramatically improve performance characteristics of today’s imaging and treatment modalities like CT scanners, positron emission tomography (PET) scanners, magnetic resonance imaging (MRI) and x-ray machines, and offers new approaches and unique technologies for selective treatment and targeted nanodrug delivery. Selective targeted delivery is reached through the conjugation of nanodrugs to antibodies designed to chemically react with the receptors of abnormal cells only. A nanodrug, selectively delivered to the tumor site, can then be activated by radiation for strong drug release, or nanoparticles can be used as a drug themselves by producing biological damage through thermal, mechanical ablations or charged particle emission.

Conclusions (continued) The nanodrug design depends on the methods of nanodrug activation. The methods of activation mean using different types of radiation for a total body scan. Under activation of nanoparticles, we mean heating them to initiate cell ablation, photoelectron emission, thermoionic emission, Compton scattering, generation of shock waves, sound waves, or mechanical waves of high pressure that are caused by the applied radiation. The ideal radiation for nanophotodynamic therapy involves deep penetration of the human body as well as enough power to activate the nanoparticles without harming the patient. The search for a universal tool for nanoparticles activation shows that very ends of the electromagnetic spectrum: x-rays on one side and RF waves on another end, are the best candidates for ideal radiation for a total body scan to activate the nanoparticles.