Targeted Drug Delivery using Nanoparticles Can Revolutionize Cancer Therapy

Surgery, chemotherapy, radiotherapy, and hormone therapy are the main common anti-tumor therapeutic approaches. However, the non-specific targeting of cancer cells has made these approaches non-effective in a large portion of patients. In particular, non-specific targeting of cancer cells also results in higher doses of drugs in order to reach the tumor region. Which in turn leads to minor to critical side effects ranging from tiredness and loss of appetite to the development of Anaemia or severe infections due to the damage the immune system suffers. Therefore, there are two main barriers in the way to reaching the tumor area with maximum efficacy. The first, inhibition of drug delivery to healthy (non-cancer) cells, and the second, the direct conduction of drugs into the tumor site. Both barriers are two sides of the same coin.

Nanoparticles (NPs) are the newly identified tools by which we can deliver drugs into tumor cells with minimum drug leakage into normal cells. While there are multiple types of NPs and there is no broad consensus regarding the definition of what nanoparticle is, most researchers agree that medical NPs are medical devices ranging from 1nm to 100nm in size.

Nanomedical research is currently a growing and promising field of scientific research. Recent studies have shown that NPs can serve as drug delivery agents by efficiently carrying and delivering drugs to specifically targeted sites and releasing them in a controlled manner. Drugs are loaded on NPs and injected into the bloodstream; Namely, NPs act as carriers.

NPs-based therapeutics are designed to modify the pharmacokinetics (PK) and pharmacodynamics (PD) of their associated drugs to prevail the physiological barriers to efficient drug delivery [2]. In 2016 alone, more than 50 nanomedicine drugs have been approved by the food and drug administration (FDA) while hundreds were submitted [1]. Improving and accelerating the investigation of nanomedicine is an active field of study.

Conjugation of NPs with ligands of cancer-specific tumor biomarkers is a potential therapeutic approach to treat cancer diseases with high efficacy. It has been shown that conjugation of NPs with molecules such as antibodies and their variable fragments, peptides, nucleic aptamers, vitamins, and carbohydrates can lead to effective targeted drug delivery to cancer cells and thereby cancer attenuation.

In traditional oral or intravascular drug delivery approaches, therapeutic factors are distributed throughout the body and only a small part of the drug reaches a tumor site. Tumor specific targeted drug delivery leads to accumulation of a drug in the tumor region and decreases the drug leakage into other healthy organs. This approach increases treatment efficacy while decreasing adverse effects [3].

There are two general drug delivery approaches including passive and active (which is also known as ligand-based) targeting [4]. NPs can usually be concentrated in the tumor area due to abnormal leaky vasculature of tumor tissue which is also known as enhanced permeation and retention (EPR) effect. The EPR effect facilitates the transition of NPs with a size of 400 nm in diameter into the surrounding tumor tissue [5]. Therefore, passive targeting depends on some pathophysiological features of tumor tissue including the abnormal vasculature, temperature, pH, and surface charge of tumor cells [4]. It is evident that some physicochemical properties of NPs such as size, surface charge, molecular weight, and hydrophobic or hydrophilic feature are crucial for passive targeting. Although passive targeting is an interesting approach, however, it suffers from serious limitations such as inefficient drug diffusion into tumor cells, the random nature of targeting, and the lack of EPR effect in some tumors [6].

One of the best ways to solve the problems of passive targeting is a conjugation of ligands of tumor-specific biomarkers with NPs which is referred to as active targeting [7]. There are several targeting moieties such as monoclonal antibodies and their variable fragments, peptides, aptamers, vitamins, and carbohydrates. It is evident that tumor specific biomarkers should be overexpressed on tumor cells to reach high specificity [8]. Following the interaction of ligands with receptors, they can internalize tumor cells through receptor-mediated endocytosis and their cargo can be released by acidic pH or enzymes [8].

To conclude, there are several anti-cancer immunotherapeutic approaches such as monoclonal antibodies, immune checkpoint inhibitors, and cancer vaccines. However, the efficacy of immunotherapy has been limited by some critical issues such as targeted delivery and controlled release. The majority of monoclonal antibodies and vaccines were not as successful as expected, which was in part related to their toxic effects due to high doses of administration. Systemic and nonspecific administration of immunotherapeutic drugs associated with the risk of systemic toxicity. Similarly, the adoptive transfer of anti-tumor T-cells may lead to autoimmunity at off-target sites [9].

To address and solve the above-mentioned limitations, extensive studies have been performed in the field of NPs-based medicine for effective and specific drug delivery in cancer therapy. The most important advantages of NPs for cancer therapy include their stability, high carrier capacity, the ability to load with both hydrophilic and hydrophobic drugs, controlled drug release, and variable routes of administration. It is also possible to load multiple drugs at the same time and monitor NPs in the body. The application of various NPs could partially help to reach this goal. Surface-modified targeted NPs can control the transport kinetics and biodistribution of cargo [10].

References

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