How nanomedicine innovations can fight cancer

Dr. Tim Sandle

Over the past two decades, nanotechnology has promised to revolutionize medicine, especially in creating ‘smart’ methods of delivering pharmaceuticals to specific targets for more effective treatment. Scientists are working with different types of nanoparticles, especially for cancer diagnosis and treatment. This article looks at some of the key innovations in this area over the past year, as well as promising future developments.

What is nanomedicine?

Nanomedicine refers to any drug that contains nanotechnology components that are artificially constructed (“artificial” distinguishes science from bacteria and viruses). Nanotechnology is a size-based concept that describes technologies measured below 1,000 nanometers (a nanometer is one millionth of a millimeter). This application builds on the empirical advantages of nanoparticles that can be manipulated to improve the behavior of drug substances.

These benefits are manifested by improved drug delivery. This overcomes her three obstacles that conventional medicine faces.

• Some types of drugs are poorly soluble in water and the human body struggles to absorb enough to treat symptoms.
• Some drug molecules are well absorbed, but often the body removes the drug before it has had enough time to provide benefit or before side effects are likely to occur. To do.
• Drugs often miss their intended target or are delivered to their intended target or to healthy cells, causing unintended damage to other parts of the body.

This is because nanotechnology overcomes the problem of absorption due to drug size, and nanoparticles can hold drugs that would otherwise be insoluble or rapidly degrade in the bloodstream firmly on the surface of the particles. . Additionally, the small size of nanoparticles can overcome biological barriers such as membranes, skin, and small intestine that normally prevent drugs from reaching their targets.¹

In terms of delivering the drug in the required timeframe, the use of nanoengineered drug carriers enables sustained release of the active ingredient. Nanotechnology also enables more precise drug delivery, using drugs that are specifically targeted to areas of the body in need of treatment.

Nanoparticles of active ingredients are usually coated with multiple layers of biomolecules (such as protein coronas). This outer layer modifies the nanoparticles’ physiochemical properties, pharmacokinetics, and toxicity profile, enabling targeted delivery and increased survival time in the body.²

Chicken or Egg: Need Nanostructural Innovation or the Right Drug Candidate First?

Despite the above advantages, nanomedicine has not been successful in treating cancer. This is mainly due to poor clinical translation from preclinical models to cancer patients.³ To overcome this, nanoparticles need to be further enhanced to protect the pathways that nanomedicine must follow in the human body.

Scientists at Harvard’s Wyeth Institute have created more stable nanostructures that can be assembled into biomolecules with different functions. This includes the development of DNA nanostructures that can bind biomolecules and assemble into multifunctional structures. A specially developed “DNA origami” is programmed to assemble into rigid square lattice blocks. One such DNA nanostructure is engineered to create a branched structure with four ends. Researchers have managed to combine and collect various antibodies that can guide the body’s T cells to attack cancer cells more intensively.^Four The DNA nanostructures are sufficiently stabilized by coating the DNA with a small-molecule, discreet neutralizing agent called PEG-oligolysine. This positively charged chemical covers multiple negative DNA charges at once, creating a stable ‘electrostatic network’. Stability is further enhanced by applying glutaraldehyde as a chemical cross-linking reagent.

Alternatives to DNA are artificial oligonucleotides that can be modified to form nanostructures. One example is from Aarhus University and uses acyclic L-threoninol nucleic acid (aTNA). It is created when a naturally occurring sugar molecule (deoxyribose) is replaced with an artificial sugar molecule (acyclic L-threoninol). This strengthens the overall structure and minimizes the potential for breakdown of molecules in the blood. A further advantage is that these oligonucleotides do not provoke an immune response. Biomolecules with high specificity for breast cancer cells are being tested using engineered oligonucleotides.^Five

Improving the robustness of nanostructures remains an academic subject unless new drug candidates are developed. This area of ​​research is gaining momentum, including at the University of Arkansas, which has developed a drug candidate that kills triple-negative breast cancer cells, an advanced cancer that cannot be treated with receptor-targeted therapies. This involves the co-formation of a relatively new class of nanomaterials called organometallic frameworks with photodynamic therapeutic drugs. The resulting compound is a nanoporous material that targets and kills tumor cells.⁶

Photodynamic therapy uses photosensitizers that, when exposed to light, produce toxic reactive oxygen species that kill cancer cells. A critical step is the bioconjugation of nanomaterials with drug ligands (binding molecules).

New FDA guidance helps move the field forward

As with any new medical innovation, a regulatory framework is required and the FDA recently issued guidance.⁷ Development of nanotechnology for use as active or inactive ingredients, including carriers carrying active ingredients. This guidance should adopt a risk-based approach to promote safety and efficacy and set requirements for each drug application. There are three key risk assessment areas.

1. Product stability: Here, developers are encouraged to identify potential factors that may affect product performance, including the interaction of nanomaterial properties. This requires a scientific evaluation of the physical and chemical changes of materials during handling and storage.
2. safety: In many cases, the safety of nanomaterials cannot be fully demonstrated by existing safety data. Therefore, additional evaluation is warranted regarding exposure levels, duration of exposure, and route of administration.
3. Effectiveness: Especially for nanomaterials formed with complex structures containing multiple components or compartments, ligands and coatings.

Nanoparticle-based drug delivery systems have shown promising therapeutic effects in cancer. To be more targeted to tumors, nanoparticles must be robust enough to survive in the human body, reach the correct target, and be functionalized with appropriate drugs. A strong regulatory framework is timely and necessary to ensure specificity and protect patients from adverse effects from delivery mechanisms.

References

1. Ma, W., Saccardo, A., Roccatano, D., Aboagye-Mensah, D. others Modular assembly of proteins on nanoparticles. Nature Communications2018; 9 (1) DOI: 10.1038/s41467-018-03931-4
2. Berger, S., Berger, M., Bantz, C., Maskos, M., Wagner, E. Performance of nanoparticles for biomedical applications: an in vitro/in vivo discrepancy. biophysics review2022;3(1):011303 DOI: 10.1063/5.0073494
3. Song, S., Bugada, L., Li, R. others Albumin nanoparticles containing a PI3Kγ inhibitor and paclitaxel in combination with α-PD1 induce tumor remission in breast cancer in mice. Science Translational Medicine2022; 14 (643) DOI: 10.1126/scitranslmed.abl3649
4. Anastassacos, F., Zhao, Z., Zeng, Y., Shih. W. Glutaraldehyde cross-linking of oligolysine coating DNA origami greatly reduces its susceptibility to nuclease degradation. crowded. Chemistry.society2020, 142, 7, 3311–3315
5. Märcher, A., Kumar, V., Andersen, V. othersA functionalized acyclic (l)-threoninol nucleic acid four-way junction with high stability in vitro and in vivo. Angewandte Chemie International Edition2022; DOI: 10.1002/anie.202115275
6. Sakamaki, Y., Ozdemir, J., Perez, A. others A maltotriose-conjugated metal-organic framework for selective targeting and photodynamic therapy of triple-negative breast cancer cells and tumor-associated macrophages. advanced therapeutics2020; 2000029 DOI: 10.1002/adtp.202000029
7. FDA. Nanomaterials Guidance for Industry, U.S. Department of Health and Human Services, April 2022: https://www.fda.gov/media/157812/download

About the author:

Dr. Tim Sandle is a pharmaceutical professional with extensive experience in microbiology and quality assurance. He is the author of over 30 books related to his science of medicine, healthcare and life, as well as over 170 peer-reviewed papers and nearly 500 technical articles. Sandle has presented at over 200 events and currently he works for Bio Products Laboratory Ltd. (BPL), University of Manchester and University College He is a Visiting Professor in London and has a PhD in the pharmaceutical industry. is also a consultant. Visit his Microbiology website at https://www.pharmamicroresources.com.