The materials that are used by this technology are named nanomaterials due to their size which is within the nanometer range.

1. What Is a Nanomaterial?

Nanomaterials are chemically synthesized or assembled products that have sizes that are within the nanometer ranges, and which include dendrimers, liposomes, metal nanoparticles, nanocrystals, nanosuspensions, polymer nanoparticles, block copolymer micelles, and polymer therapeutics.

A. What is a Dendrimer?

Dendrimers are chemical structures that are generated by a repetitive assembly of molecules leading to the formation of a molecule with a central core, a network of branched molecules, and terminal functional groups at the surface responsible for the spherical form of dendrimers [1]. Dendrimers can be conjugated with drugs and detecting agents for delivery to tissues within the body.

B. What is a Liposome?

Liposomes are chemically engineered spheres that contain at least one phospholipid layer. They are usually obtained by dispersing phospholipids in water which creates vesicles named liposomes. Once loaded with drugs or DNA, liposomes can cross cellular membranes and deliver their load within the cells [2].

C. What Is a Metal Nanoparticle?

Metal nanoparticles are structures that are made of a metal core that is covered by inorganic or organic materials. Metal elements that are used in the production of metal nanoparticles include gold, aluminum, iron, silica, silver, copper, zinc, manganese, nickel, cerium, and titanium [3].

D. What Are Nanocrystals?

Nanocrystals are generated by the micronization and size homogenization of crystals into nanomer-sized particles. They are formed by a crystalline core and a stabilizer layer made of agents such as sodium lauryl sulfate, polyvinyl pyrrolidone K30, pluronics F68 and F127, Tween 80, hydrophobin, or hydroxypropyl methylcellulose.

Nanocrystals have been used in drug delivery to improve the dissolution properties of poorly soluble drug materials [4].

E. What Are Nanosuspensions?

Nanosuspensions are solid drug nanoparticles that are suspended in an aqueous vehicle to facilitate their water solubility and stability. These solid drugs may have poor aqueous solubility which affects their therapeutic efficacy and increases their toxicity [5].

F- What Are Polymer Nanoparticles?

Polymer nanoparticles are chemically synthesized molecules through the assembly and bonding of repeated chemical subunits. They are specifically made to overcome challenges associated with a carrier system such as biocompatibility, biodistribution, side-effects, and biological barriers [6]. 

G. What Are Block Copolymer Micelles?

Block Copolymer Micelles are self-assembled chemical molecules made of oppositely charged copolymers in an aqueous or organic solution. They are constituted of hydrophytic heads on the outside and hydrophobic tails on the inside. They are used as carriers for drug delivery and gene targeting [7].

H. What Are Polymer Therapeutics?

Polymer therapeutics are water-soluble polymers that are conjugated to proteins, micelles, or drugs to generate complex drugs such as polymer-protein conjugates, polymer-micelles conjugates, or polymer-drugs conjugates, respectively.

Due to their enhanced water solubility of the conjugated and reduced toxicity, polymer therapeutics are used for multi-drug delivery and wound healing applications [8].

2. What Are the Applications of Nanomedicine?

A. Nanomedicine Applications in Diagnosis

Due to their capacity for conjugation to dyes, proteins (e.g., ligands), and imaging agents, nanoparticles are used for early and accurate diagnosis and monitoring of patients via direct imaging of the tissue of patients (in vivo) or by running tests on samples from patients (in vitro) [9].

Imaging of Tissues and Organs of Patients

To enhance the contrast of structures and fluids within the body of patients, nanoparticle-based contrast agents are successfully used for imaging technologies such as MRI (Magnetic Resonance Imaging), PET (Position Emission Tomography) scan, CT (computed tomography), PAT (Photoacoustic tomography), Raman spectroscopic imaging, and multimodal imaging [10].

Diagnostic Tests Using Nanoparticles

Nanoparticles are used to produce in vitro diagnostic devices or biosensors that are used to detect and potentially measure biological reactions such as antibody binding to an antigen, nucleic acids hybridization, or ligand binding to the surface of cells [10].

B. Nanomedicine Applications in Therapy

Nanoparticles are mainly used for the delivery of drugs to patients through oral or skin applications, or by injection. For instance, the liposome product Doxil® is used to deliver the chemotherapeutic drug Doxorubicin to tumors with reduced toxicity for the heart and kidneys [11].

For the treatment of metastatic breast cancer and non-small-cell lung cancer, the polymer mPEG-PLA is being used for the delivery of the chemotherapeutic drug Paclitaxel [12][13]. Gold nanoparticles that bind to cancer cells can be used to tag these cells for irradiation by infrared laser leading to their death [14].

3. Frequently Asked Questions about What Are the Applications of Nanomedicine?

What is nanomedicine?

Nanomedicine is a field of medical science that utilizes nanotechnology for diagnosis, treatment, and monitoring of diseases at the molecular level. It involves the application of nanoscale materials and devices to address medical challenges.

What are the applications of nanomedicine?

Nanomedicine has diverse applications in various areas of healthcare, including drug delivery, imaging, diagnostics, regenerative medicine, and personalized medicine.

How does nanomedicine improve drug delivery?

Nanoparticles can be designed to encapsulate drugs and deliver them to specific target sites in the body, enhancing drug efficacy while minimizing side effects. They can also improve the bioavailability and stability of drugs.

Can nanomedicine be used for cancer treatment?

Yes, nanomedicine holds great promise for cancer therapy. Nanoparticles can be engineered to selectively target cancer cells, deliver chemotherapeutic agents directly to tumors, and enhance imaging for early detection and monitoring of cancer progression.

What role does nanomedicine play in diagnostics?

Nanotechnology enables the development of highly sensitive diagnostic tools, such as biosensors and imaging agents, for early detection of diseases. These nanoscale devices can detect biomarkers at very low concentrations, allowing for early intervention and treatment.

How does nanomedicine contribute to regenerative medicine?

Nanomaterials can mimic the extracellular matrix and provide scaffolds for tissue regeneration. They can also deliver growth factors and therapeutic molecules to promote tissue repair and regeneration in conditions such as wound healing and tissue engineering.

Is nanomedicine used in personalized medicine?

Yes, nanotechnology plays a crucial role in personalized medicine by enabling targeted therapies tailored to individual patient characteristics. Nanoparticles can deliver drugs based on specific genetic markers or biomarkers, leading to more effective and personalized treatment strategies.

What are some challenges in the development of nanomedicine?

Challenges include ensuring the safety and biocompatibility of nanomaterials, optimizing their pharmacokinetics and biodistribution, and scaling up production methods. Regulatory considerations and ethical implications also need to be addressed for the widespread adoption of nanomedicine.

Are there any approved nanomedicine products on the market?

Yes, there are several nanomedicine products approved for clinical use, including nanoparticle-based drug delivery systems, imaging agents, and medical devices.

Examples include Abraxane (nanoparticle albumin-bound paclitaxel) for cancer treatment and Feraheme (ferumoxytol) for iron deficiency anemia.

Conclusion

Nanomedicine is a relatively new medical application that already has significant impacts on the diagnosis and drugs delivered to patients. Although it is still a domain of science fiction, some scientists suggest the futuristic possibility of creating nanorobots that can repair or detect damages and infections.

References

[1] Duncan, R. and Izzo, L., 2005. Dendrimer biocompatibility and toxicity. Advanced drug delivery reviews, 57(15), pp.2215-2237.

[2] Akbarzadeh, A., Rezaei-Sadabady, R., Davaran, S., Joo, S.W., Zarghami, N., Hanifehpour, Y., Samiei, M., Kouhi, M. and Nejati-Koshki, K., 2013. Liposome: classification, preparation, and applications. Nanoscale research letters, 8(1), pp.1-9.

[3] Schrand, A.M., Rahman, M.F., Hussain, S.M., Schlager, J.J., Smith, D.A. and Syed, A.F., 2010. Metal‐based nanoparticles and their toxicity assessment. Wiley interdisciplinary reviews: Nanomedicine and Nanobiotechnology, 2(5), pp.544-568.

[4] Tuomela, A., Hirvonen, J. and Peltonen, L., 2016. Stabilizing agents for drug nanocrystals: effect on bioavailability. Pharmaceutics, 8(2), p.16.

[5] Pawar, S.S., Dahifale, B.R., Nagargoje, S.P. and Shendge, R.S., 2017. Nanosuspension technologies for delivery of drugs. J Nanosci Nanotechnol, 4, pp.59-66.

[6] Daglar, B., Ozgur, E., Corman, M.E., Uzun, L. and Demirel, G.B., 2014. Polymeric nanocarriers for expected nanomedicine: current challenges and future prospects. RSC Advances, 4(89), pp.48639-48659.

[7] Kataoka, K., Harada, A. and Nagasaki, Y., 2001. Block copolymer micelles for drug delivery: design, characterization and biological significance. Advanced drug delivery reviews, 47(1), pp.113-131.

[8] Aderibigbe, B.A. and Mukaya, H.E., 2017. Polymer Therapeutics: Design, Application, and Pharmacokinetics. In Nano-and Microscale Drug Delivery Systems (pp. 33-48). Elsevier.

[9] Murthy, S.K., 2007. Nanoparticles in modern medicine: state of the art and future challenges. International journal of nanomedicine, 2(2), p.129.

[10] Sim, S. and Wong, N.K., 2021. Nanotechnology and its use in imaging and drug delivery. Biomedical reports, 14(5), pp.1-9.

[11] Barenholz, Y.C., 2012. Doxil®—the first FDA-approved nano-drug: lessons learned. Journal of controlled release, 160(2), pp.117-134.

[12] Shi, M., Gu, A., Tu, H., Huang, C., Wang, H., Yu, Z., Wang, X., Cao, L., Shu, Y., Yang, R. and Li, X., 2021. Comparing nanoparticle polymeric micellar paclitaxel and solvent-based paclitaxel as first-line treatment of advanced non-small-cell lung cancer: an open-label, randomized, multicenter, phase III trial. Annals of Oncology, 32(1), pp.85-96.

[13] Lee, K.S., Chung, H.C., Im, S.A., Park, Y.H., Kim, C.S., Kim, S.B., Rha, S.Y., Lee, M.Y. and Ro, J., 2008. Multicenter phase II trial of Genexol-PM, a Cremophor-free, polymeric micelle formulation of paclitaxel, in patients with metastatic breast cancer. Breast cancer research and treatment, 108(2), pp.241-250.[14] Amendoeira, A., García, L.R., Fernandes, A.R. and Baptista, P.V., 2020. Light irradiation of gold nanoparticles toward advanced cancer therapeutics. Advanced Therapeutics, 3(1), p.1900153.

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To introduce or replace defective genes, this approach involves using viral or non-viral vectors to insert healthy copies of genes into the cells of affected people to re-establish their normal function within the targeted cells, tissues, and organs [1].

I. What is CRISPR Gene Editing?

Inserting healthy copies or correcting mutations genes rely on the use of genetic engineering techniques, such as the CRISPR gene editing method that can be specifically designed to recognize the defective gene, cut it at the desired location or replace it with a healthy and functional gene [2].

1- What Is Crispr?

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences that are originally found in the genomes of microorganisms such as bacteria or archaea.

Because bacteria and archaea can be infected by a virus known as bacteriophage (phage), CRISPR sequences are used by bacteria and archaea to flank or tag the bacteriophage DNA that has been integrated into their genome by the bacteriophage.

CRISPR is used to quickly recognize and destroy the bacteriophage DNA that was inserted into their genome. Therefore, CRISPR is used as a form of acquired immunity for bacteria and archaea [3].

2- How Does Crispr Gene Editing Work?

When an infection by a bacteriophage happens, which involves the insertion of the bacteriophage DNA into the bacteria or archaea genome, bacteria or archaea produce an enzyme known as CAS9 (CRISPR-Associated protein 9) that recognize, cleave, and remove the CRISPR sequences that flank the bacteriophage DNA [3].

Therefore, the CRISPR/Cas9 technology can be used to specifically target defective or mutated genes within the cells of the human body by directing Cas9 directly to these genes are then recognized and cleaved by Cas9.

However, in the human body, Cas9 requires guidance towards the gene of interest to be cleaved.

In this case, the CRISPR/Cas9 technology uses specific RNA molecules known as RNA guides (gRNA) that contain the specific information about the gene of interest within the cells of the body and that will help Cas9 to recognize that specific gene and cleave it.

II. How Is Crispr Delivered in the Body?

Viruses or non-viral vectors are considered for the delivery of Cas9 and the gRNA in the cells of the body.

1- What Are Viral Vectors?

Viruses have the capacity to bind and introduce their genetic material to the host cells. Once the genetic material is introduced, new viruses are made using the infected cells by hijacking their ability to produce proteins.

Therefore, after making these viruses incapable of causing disease by removing some parts of their genetic material, these can be used to introduce Cas9 and gRNA to cleave and remove the gene of interest.

• Retroviruses

Retroviruses are RNA viruses which means that their genome is not made of DNA but of RNA.

When these viruses enter the host cells and with the help of a viral enzyme known as transcriptase, they start making DNA copy from the RNA.

The newly generated viral DNA is then integrated into the host genome by another enzyme known as integrase.

Once integrated into the genome of the host cells, the viral DNA is transcribed in a similar way as the host DNA leading to the production of proteins and enzymes that help the multiplication of the virus.

Therefore, retroviruses can be used to introduce Cas9 and gRNA within the host cell which then go and recognize and cleave the gene of interest.

The advantage of using retroviruses for the delivery of Cas9 and gRNA is in their capacity to infect both dividing and non-dividing cells within the body as they can replicate their genes when the infected host cell is dividing.

• Adenoviruses

Unlike retroviruses, adenoviruses are DNA viruses which means that their genome is made of DNA. Adenoviruses do not integrate their DNA in the host genome as they do not have an integrase.

This inability of integrating the DNA of the host, makes their replication limited as their genes are not replicated when the infected host cell is dividing.

Therefore, adenoviruses are best used for introducing Cas9 and gRNA in cells that do not divide, and therefore, are fully differentiated.

2- What Are Non-Viral Vectors?

Although the use of viruses for the delivery of Cas9 and gRNA into the host cells is an efficient method, they also have limitations such as immunogenicity of the host (immune response) and their production at large scales.

These limitations can be overcome through the use of non-viral vectors.

• Injection of Naked DNA

Although the efficiency is limited, this method involves the injection of DNA into the muscles, which is then integrated by the cells.

• Lipoplexes

Lipoplexes are liposomes that form complexes with nucleic acids, such as DNA and RNA, for delivery into the cells of the host. Because of their lipid nature, lipoplexes fuse with the cell membranes of the host cells and deliver their nucleic acids.

• Polymersomes

Polymersomes are synthetic liposomes that also form complexes with nucleic acids for delivery to the host cells.

• Nanoparticles

Nanoparticles are chemically synthesized or assembled products that have sizes that are within the nanometer ranges, and which include dendrimers, liposomes, metal nanoparticles, nanocrystals, nanosuspensions, polymer nanoparticles, block copolymer micelles, and polymer therapeutics.

Due to their small size, nanoparticles are used to form complexes with nucleic acids to ease their delivery to host cells.

• Virosomes

Virosomes are made of liposomes that have nucleic acids (DNA, RNA) and viral proteins to facilitate their recognition and intake by the host cells.

III. Medical Applications of CRISPR Gene Editing

Gene therapy has been proposed for the treatment of several genetically related diseases, including cancer, hemophilia, cystic fibrosis, amyotrophic lateral sclerosis, age-related macular degeneration, sickle cell anemia, progeria, beta-thalassemia, Huntington disease, and Duchenne’s muscular dystrophy [1] [5].

However, so far, clinical trials to cure beta-thalassemia and sickle cell disease in human patients have shown promising results [4].

Conclusion

Although gene therapy is a promising medical approach, challenges regarding its efficacy, safety, and specificity must be further investigated before its use in clinics. Nonetheless, this therapy is highly fascinating and could provide significant hope in developing medical cures against deadly genetic diseases.

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