Nanoparticle (Smart Drugs) Delivery Systems in Cancer Treatment

Despite significant advances in medicine, cancer is among the leading causes of death worldwide and is a serious obstacle to longer life expectancy. Worldwide, there are around 20 million new cases and 10 million cancer-related deaths annually. For example, one out of every eight women (12%) in their lifetime is diagnosed with breast cancer, which is the second leading cause of cancer death after lung cancer.

On the other hand, advances in technology, meanwhile in nanotechnology, continue at a dizzying pace. In the medical field, we see the most obvious and current example of this in the SARS-CoV-2 epidemic, which can be considered a human disaster. Lipid nanoparticles play a vital role both for the protection of the mRNA vaccine active substance, which has been used routinely in medicine for the first time against this virus, and for its transport to the right place in the cell.

Cancer Formation and Immunoediting

The transformation of normal cells in our body into cancer occurs as a result of successive mutations in genes called oncogene, tumor suppressor gene and DNA repair gene, depending on a number of factors.

Fortunately, our immune system starts a great fight against these cancer cells and eliminates most of them in the first step. The struggle between the cells starting to become cancerous and the immune system can be summarized in three phases, which we can define as 3E of immunoediting (Elimination, Equilibrium and Escape) (Figure-1):

1. Elimination (both the innate and adaptive immune system together detect and destroy early tumors before they become clinically visible),

2. Equilibrium (the immune system holds the tumor in a state of functional dormancy) and

3. Escape (the immune system fails to restrict tumor outgrowth and tumor cells emerge causing clinically apparent disease)

Treatment In Cancers

Standard methods in cancer treatment:

1. Chemotherapy

2. Radiotherapy

3. Surgical treatment

The place of these methods in cancer treatment is very important. On the other hand, despite intensive studies, it is clear that very serious side effects such as serious toxicity, fibrotic tissue development, problems due to suppression of the immune system, and treatment resistance cannot be avoided.

The main way of achieving real success in cancer treatments depends on the fact that the given drugs reach the cancer cells as much as possible without affecting the healthy tissues. When this situation is achieved, a great improvement will be observed in the quality and duration of life of the patient. For this reason, applications such as vaccines, biological, hormonal, targeted and gene therapy have been increasingly used according to the type and characteristics of cancer.

Nanoparticles For Use In Therapeutic

Substances called nanoparticles (NP) are generally very small in size, as much as 10-100 nm, and are used in various fields of nanotechnology. In the meantime, thanks to its ability to load various substances on it, it has a field of use in different fields of medicine such as cancer diagnosis and treatment, gene therapy, infections, dentistry. In fact, nanoparticle carrier applications to prevent transplantation rejection and post-transplant infection development are among the studies that have just been emphasized in recent years.

Their unique features give them different advantages over classical methods. For example, with directional NPs, also called second generation, an active ingredient loaded on it can be selectively directed to a desired site. Therefore, the active substance reaches more intense concentrations in the desired area rather than in other parts of the body. As a result, maximum effect is achieved with less doses of active ingredient and side effects are extremely reduced.

NPs can have different properties such as micelles, liposome, and polyester. the For NP to be used in the application, some properties such as the size, the stability of the prepared systems, the release properties of the loaded substance, its bio-distribution, its effectiveness and the non-toxicity of the degradation products are chosen according to the purpose.

NPs are loaded with toxic agents, various drugs, DNA/RNA and imaging agents according to the purpose. The loading capacity of a NP and even the release of the loaded substance in the target tissue vary depending on the matrix structure and the solubility of the active substance to be loaded on it. Depending on these capacities, they can be made multifunctional and synergy can be achieved in treatment by adding active ingredients for different steps in a disease formation mechanism pathway. In addition, the possibility of combination therapy arises by adding substances that are effective with different mechanisms. Again, thanks to the added biomarkers, the amount of drug accumulated in the target area can be displayed. By this way, diagnosis and treatment can be achieved at the same time. Moreover, after drug-loaded NP applications, the immune system’s fight against cancer accelerates even more (Figure-3).

Thanks to the important developments in the field of nano-oncology, drug concentrations reaching cancer cells can be increased and the toxic effect on healthy cells can be minimized through targeting, which we can also call smart drug delivery method. Moreover, combination therapies, which can be applied with different NP-based strategies, have an important therapeutic potential due to their synergistic effects and greatly reduced side effects.

References:

  1. Sung H, Ferlay J, Rebecca L, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 0:1–41, 2021.
  2. Mukherjee S,  Liang, Veiseh O. Recent Advancements of Magnetic Nanomaterials in Cancer Therapy. Pharmaceutics 12: 147, 2020.
  3. Awasthi R, Roseblade A, Hansbro PM, et al. Nanoparticles in Cancer Treatment: Opportunities and Obstacles. Curr Drug Targets 19:1696-1709, 2018.
  4. Sharma R, Mody N, Agrawal U, et al. Theranostic Nanomedicine; A Next Generation Platform for Cancer Diagnosis and Therapy. Mini Rev Med Chem 17:1746-1757, 2017.
  5. Belyanina I, Kolovskaya O, Zamay S, et al. Targeted Magnetic Nanotheranostics of Cancer. Molecules 22: 975, 2017.
  6. Tiwari G, Tiwari R, Sriwastawa B et al. Drug delivery systems: An updated review. Int J Pharm Investig 2: 2–11, 2012.
  7. Wu M, Huang S. Magnetic nanoparticles in cancer diagnosis, drug delivery and treatment. Molecular And Clinical Oncology 7: 738-746, 2017.