Razi Journal of Medical Sciences

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Moshref javadi M, Soleimani N. Therapeutic and anticancer effects of nanoparticles. RJMS 2020; 27 (10) :115-134
URL: http://rjms.iums.ac.ir/article-1-6107-en.html

Cancer is a commonly lethal disease that causes many deaths every year around the world. Cancer, the uncontrolled proliferation of cells where apoptosis is greatly disappeared, requires very complex process of treatment. Because of complexity in genetic and phenotypic levels, it shows clinical diversity and therapeutic resistance. A variety of approaches are being practiced for the treatment of cancer each of which has some significant limitations and side effects. Based on the actual data, the International Agency for Research on Cancer (IARC) estimates ~13.1 million deaths associated to cancer by 2030. It is becoming clear for many researchers that the low survival rate is due to the lack of adequate drug delivery systems and not due to the lack of potent, natural, or synthetic anti tumoral agents. Therefore, there is a real need to develop carriers and delivery systems which would be able to deliver the chemotherapeutic agents only at the specific target site and improve the efficiency of treatment and consequently limiting the unwanted systemic side effects. Existing therapies have failed to meet the therapeutic need for all types of cancer. Therefore, the use of new technologies in cancer prevention and treatment can be helpful. In recent years, extensive research has been done on nanoparticles. The advent of nanotechnology has a profound impact on many areas of health care and scientific research. Common cancer therapies, including chemotherapy, radiation, and surgery, may reduce the size of the tumor, but the effect is transient and has no positive effect on patient survival. In addition, chemotherapy drugs damage the immune system and reduce white blood cells, which makes patients more susceptible to infections. Sometimes chemotherapy reduces the number of red blood cells, which can make the patient feel very tired, short of breath, dizzy and light.Therefore, replacing more effective, specific and less side effects with higher anti-cancer activity is a dominant issue in clinical oncology. Greater targeting selectivity and better delivery efficiency are the 2 major goals in the development of therapeutic agents or imaging contrast formulations. Ideally, a therapeutic drug would be selectively enriched in the tumor lesions with minimal damage to normal tissues. A rational approach to achieve these goals is to conjugate therapeutic drugs with monoclonal antibodies (mAbs) or other ligands that selectively bind to antigens or receptors that are usually abundantly or uniquely expressed on the tumor cell surface. Several ligand‐targeted therapeutic strategies, including immunotoxins, radioimmunotherapeutics, and drug immunoconjugates, are being developed. These conjugated agents have demonstrated promising efficacy compared with conventional chemotherapy drugs in preclinical and clinical trials. Furthermore Nanoparticles attached to cancer marker targeted antibodies could detect cancer at earlier phases of cancer development, better than existing methods. Novel designed nanomaterials could carry payload of cytotoxic drugs or lethal toxins inside cancer cells and defy host immune defence and protect normal cells, thereby could result in cancer cure with least side effects. For example; Radiation treatment is non-specific; therefore, intratumour injection of nanomaterials could generate short-range electrons inside tumour and enhance radiation lethality to tumour and no effects to the normal tissues. Topical or parenteral injection of nanomaterials during surgical procedure could add surgeons to precisely take out tumour with useful surgical margin. Nanotechnology is a vast field of unexplored science which is unknown to medical field could possibly redefine cancer treatment. Rapid growth in nanotechnology toward the development of nanomedicine agents holds massive promise to improve therapeutic approaches against cancer. Nanomedicine products represent an opportunity to achieve sophisticated targeting strategies and multifunctionality. Nowadays, nanoparticles (NPs) have multiple applications in different branches of science. In recent years, NPs have repetitively been reported to play a significant role in modern medicine. They have been analyzed for different clinical applications, such as drug carriers, gene delivery to tumors, and contrast agents in imaging. A wide range of nanomaterials based on organic, inorganic, lipid, or glycan compounds, as well as on synthetic polymers has been utilized for the development and improvement of new cancer therapeutics. Nanotechnology could provide a tremendous platform to boost the efficacy of therapeutic systems from the bench to clinical applications.The gradual maturation of nanotechnology has received widespread attention not only for cancer treatment but also for a wide variety of applications, especially for drug delivery and diagnostic and imaging applications. There are different types of nanoparticles available and choosing the right carrier according to demand is a key issue. Nanotechnology has been extensively studied and exploited for cancer treatment as nanoparticles can play a significant role as a drug delivery system. Compared to conventional drugs, nanoparticle-based drug delivery has specific advantages, such as improved stability and biocompatibility, enhanced permeability and retention effect, and precise targeting. In addition, nanoparticle-based drug delivery systems have been shown to play a role in overcoming cancer-related drug resistance. The mechanisms of cancer drug resistance include overexpression of drug efflux transporters, defective apoptotic pathways, and hypoxic environment. Nanoparticles targeting these mechanisms can lead to an improvement in the reversal of multidrug resistance. Furthermore, as more tumor drug resistance mechanisms are revealed, nanoparticles are increasingly being developed to target these mechanisms. Moreover, scientists have recently started to investigate the role of nanoparticles in immunotherapy, which plays a more important role in cancer treatment. The nanoparticles are quite close in size to the biological molecules and can easily penetrate into the cell. Nanoparticles can also have different surface properties by binding protective ligands to increase the resistance of the nanoparticles to the immune system and to increase their circulation and even to bind specific ligands to the target tissues tract. Moreover, nanomaterials can also be designed for increased drug loading, improved half-life in the body, controlled release, and selective distribution by modifying their composition, size, morphology, and surface chemistry. Recent progress in cancer nanotechnology raises exciting opportunities for personalized oncology in which diagnosis and treatment are based on the molecular profiles of individual patients. In this review, we will address first the types and characteristics of nanoparticles and the roles of nanoparticles and hybrid nanoparticles for drug delivery in chemotherapy, targeted therapy, and immunotherapy and describe the targeting mechanism of nanoparticle-based drug delivery as well as its function on reversing drug resistance.