Nanotechnology uses devices that are on the scale of nanometers (nm), usually between 1 – 100 nm1. A nanometer is one billionth of a meter. A strand of human DNA has a diameter of about 2.5 nm, and a single human hair is 80,000 to 100,000 nm wide. It has been called a key pillar in driving the next industrial revolution, often referred to as Industry 4.0 or the Fourth Industrial Revolution. Nanomedicine uses nanotechnology to help prevent and diagnose diseases, while providing targeted drug delivery and personalized therapies. Nanoscale drug delivery systems can target specific cells or tissues. This minimizes or eliminates adverse side effects while making therapies more effective. This is especially true for cancer.

Two of the first nanodrugs that were approved by the FDA in the USA for treating cancer are Doxil and Abraxane. Doxil contains the chemotherapeutic agent called doxorubicin. It is packaged inside lipid nanoparticles and a non-toxic polymer called polyethylene glycol (PEG). It is used to treat many types of cancer. Abraxane contains the chemotherapeutic agent called paclitaxel. It is in nanoparticles made from a natural protein found in the blood called albumin. It is used to treat several types of breast cancer.

Lipid nanoparticles became famous when they were used to make COVID-19 vaccines based on messenger RNA (mRNA technology) 2. They are spherical and usually contain a mixture of phospholipids, cholesterol, ionizable lipids, and lipids with PEG bound to them. They are used for systemic, intramuscular, intratumoral, and pulmonary delivery of mRNA. Some examples of other FDA-approved nanomedicines include Mycocet©, Marqibo©, Ambisome©, Onivyde®, Genexol PM©, Eligard,® and Vyzeos©, for breast cancer, acute lymphoblastic leukemia (ALL), fungal infections, pancreatic cancer, metastatic breast cancer, prostate cancer, and acute myeloid leukemia (AML), respectively 3.

CALAA-01 is the first nanodrug that delivers small interfering RNA (siRNA) to specific targets. It uses cyclodextrin-containing polymers to form nanoparticles of approximately 70 nm. Vyxeos (CPX-351) was developed by Jazz Pharmaceuticals, Palo Alto, CA, USA. It is the first FDA-approved dual-drug containing liposomal nanomedicine that delivers cytarabine and daunorubicin in a 5:1 molar ratio. It is being tested for its ability to treat AML. Nanotherm is a magnetic nanoparticle developed by MagForce Nanotechnologies AG in Germany. This drug is made of superparamagnetic iron oxide nanoparticles (SPIONs) coated with amino silane and is used for cancer thermal therapy. The treatment uses localized heating (41–46 ◦C) to make cancer cells more sensitive to therapy or applies higher heat (over 46 ◦C) to destroy them and the surrounding tissues.

Nanotechnology has produced inorganic multifunctional nanoparticles (IMNPs) such as gold nanoparticles (Au NPs), quantum dots, mesoporous silica NPs, copper NPs, and magnetic 4. They are used for therapy and diagnosis in the field of theranostics. Much progress has been made in using IMNPs for imaging and therapy of multidrug-resistant cancers. They can monitor the concentrations of biomarkers and other important biochemicals. The field of nanomedicine has benefited from using advanced diagnostic imaging and therapy. Various nanoplatforms contain drugs that are released into the specific target. They can also monitor biomarkers to follow the progress of the therapy. This dual-purpose approach is called nanotheranostics. It must detect biomarkers easily, be stable, be able to cross biological barriers, and demonstrate safety. They often contain specialized payload carriers and therapeutic drug transporters that target specific ligands and emit signals that are detected. IMNPs are becoming a useful tool in cancer therapy. They have significant advantages over conventional treatment methods and are used in diagnostic applications, including magnetic resonance imaging (MRI), computed tomography (CT), and fluorescence imaging, due to their strong optical and magnetic properties.

Recently, the KRISS Nanobio Measurement Group described a new nanomaterial that provides treatment while monitoring cancers. It also activates the immune response system. The nanomaterial is a triple-layer nanodisk (AuFeAuNDs), with iron (Fe) inserted between gold (Au) 5-7. This triple-layer nanodisk has better structural stability compared to traditional spherical materials. By applying a magnet near the tumor site, the magnetic properties of the iron allow the nanomaterial to be attracted. It uses photoacoustic (PA) imaging. This enables real-time observation of both the tumor's location and the drug delivery process. PA visualizes vibrations (ultrasound) generated by heat when a laser is directed at the nanodisk. This enables treatment to be performed at the optimal time - when the nanomaterial reaches the tumor site. This maximizes its effectiveness.

Nanodisks made from a triple layer of iron placed between two layers of gold (AuFeAu) were fabricated using nanoimprint lithography. That is, there is a very thin layer of Fe between two layers of Au. They modified the nanodiscs with polyethylene glycol to improve biocompatibility. The Fe layer between the Au layers improves the photostability of the overall structure. These trilayer uniform nanodisks have a higher magnetic moment than bulk Fe, making them a stronger magnet. Also, AuFeAu nanoparticles can have perpendicular magnetic anisotropy. That is, the magnetization prefers to be oriented perpendicular to the plane in which the particle lies. Photoacoustic therapy guided by improved imaging improves spatiotemporal control in cancer treatment. This is particularly effective using an infrared laser with a wavelength between 1000-1350 nm. This is called the second near infrared (NIR-II) window. This wavelength range is good for bioimaging because it penetrates human tissue better, as it is scattered less and not absorbed as much compared to shorter wavelengths.

These nanodisks also enable chemodynamic therapy (CDT) that can work synergistically with other therapies. CDT kills cancer cells by producing hydroxyl radicals through a chemical reaction called the Fenton reaction. That is, Fe reacts with hydrogen peroxide that is produced naturally by oxidative metabolism. This produces a deadly hydroxyl radical that kills cells. Thus, the Fe layer improves targeting, therapy, ferroptosis (cancer cell death caused by Fe), and immunogenic cell death (ICD). They initiate ICD by releasing DAMPs, leading to the augmentation of cytotoxic T cells6.

These Janus-type gold nanodiscs also have an asymmetrically integrated polyaniline (PANI) structure. The polyaniline was placed on just one face of the nanoparticle. PANI enhances photothermal conversion efficiency in response to NIR-II light. PANI is a conductive polymer that has been widely studied for its ability to tune the optical properties of nanomaterials. AuPANI NDs are potent PA imaging−guided photothermal therapy agents when irradiated at 1064 nm. The nanodiscs were optimized for NIR-II photothermal therapy and multimodal imaging. Their dual-faced, asymmetric structure improves stability and multifunctionality. The AuPANI nanodiscs can produce images in deep tissues using photoacoustic imaging up to 15 mm, while enabling highly sensitive positron emission tomography imaging through radiolabeling7.

Notes

1 The Marvel of Nanotechnology on Meer.
2 Vaccines based on modern RNA technology on Meer.
3 Clinical Applications of Targeted Nanomaterials on MDPI.
4 Recent progress in multifunctional theranostic inorganic nanomaterials for cancer diagnostic imaging and therapy on ScienceDirect.
5 Multifunctional nanodisk enables cancer diagnosis, treatment and immune activation on News Medical.
6 Au/Fe/Au trilayer nanodiscs as theranostic agents for magnet-guided photothermal, chemodynamic therapy and ferroptosis with photoacoustic imaging on ScienceDirect.
7 Janus Gold Nanodiscs with an Asymmetrically Positioned Polyaniline Nano-Urchin for Photothermal Therapy and Multimodal Imaging in the Second Near-Infrared Window on ACS Applied Materials & Interfaces.