Associate editor: F. Tarazi
Emerging nanomedicines for early cancer detection and improved treatment: Current perspective and future promise

https://doi.org/10.1016/j.pharmthera.2010.07.007Get rights and content

Abstract

The application of nanotechnology to medicine, commonly referred to as ‘nanomedicine’, has the potential to transform our approach to human health and disease. Research at the nanoscale level affords the opportunity to address some of the most confounding human diseases at the molecular level, with the potential for significant improvements in disease prevention, diagnosis and treatment. Rapid advances and emerging technologies in nanoscale systems, particularly nanoparticles, are having a profound impact on cancer diagnosis, treatment and monitoring. The development of nanoparticulate systems that offer improved chemotherapeutic delivery through increased solubility and sustained retention times is an area of intense focus in nanomedicine. In addition, active targeting of nanoparticles through conjugation of tumor-specific cell surface markers such as tumor-specific antibodies or ligands can enhance the efficacy of nanoparticle drug delivery systems while significantly reducing toxicity. Perhaps some of the most exciting advances in nanomedicine are multifunctional nanoparticulate systems for simultaneous imaging of tumor mass and drug delivery. In a relatively short period of time, nanomedicine has already begun to have a strong presence in the global market. This review provides a comprehensive summary of recent progress in nanomedicine as it relates specifically to nanoparticles and anticancer drug delivery. Research into different nanoprobes for cancer detection/imaging will also be discussed. Lastly, the future of this growing and dynamic field and its potential impact will be discussed.

Introduction

Cancer has one of the highest mortality rates in the United States and worldwide despite tremendous effort by researchers and industry in this field. Cancer accounted for upwards of 7,021,000 deaths in 2007 worldwide, and is the second leading global killer, accounting for 12.5% of all deaths (Garcia et al., 2007). The World Health Organization estimates that cancer will become the leading cause of death worldwide by the year 2010 (Mah, 2008). Although there have been significant advances in cancer treatment over the past several decades, current diagnostic and therapeutic approaches rely predominantly on invasive (i.e. random biopsies and surgery) and crude, non-specific techniques such as irradiation and chemotherapeutic agents (Duong and Mousa, 2009, Clifton and Charles, 2010, Basaran et al., in press). Cancer continues to be almost uniformly fatal, and current therapeutic modalities have yet to significantly improve the dismal prognosis of this disease.

The application of nanotechnology to medicine, or nanomedicine, has the potential to profoundly impact numerous aspects of health care in general, and cancer diagnosis and treatment specifically. The prefix ‘nano’ comes from the Greek ‘dwarf’. In terms of size constraints, the National Nanotechnology Initiative defines nanotechnology as the science of materials and phenomena in the range of 1 to one hundred nanometers (nm, 10−9 m) (http://www.nano.gov). Nanoparticles represent a true nanoscale system, typically being no greater than one to several hundred nanometers in diameter. Nanoparticles can be engineered to incorporate a wide variety of chemotherapeutic agents and target the delivery of these agents directly and specifically to the tumor site for better efficacy and less toxicity (Brannon-Peppas & Blanchette, 2004, Koo et al., 2005, Sinha et al., 2006, Kim et al., 2010, Wang and Thanou, 2010, Yu et al., 2010). Moreover, the size and surface-tunable properties of nanoparticles can be manipulated to prevent their opsonization, thus providing a mechanism for sustained blood circulation (Torchilin, 1998, Moore et al., 2000, Moghimi et al., 2001, Senthilkumar et al., 2008, Prencipe et al., 2009). These properties of nanoparticles have made them one of the most extensively studied systems in nanomedicine.

One of the most critical points in cancer treatment is early stage diagnosis, before tumor cells metastasize. Most types of cancer can be treated effectively if they are detected at an early stage, and the patient will achieve full recovery. Unfortunately, early stage diagnosis remains a significant challenge, as clinical symptoms rarely manifest before cancer progresses to a fatal stage. Minimally invasive, user friendly technologies for efficient detection and prognosis of cancer are urgently needed. To this end, many types of nanoparticle-based technologies are in development for improved diagnostic imaging of a variety of cancer types, as well as targeted delivery of chemotherapeutic drugs. Targeted drug delivery will help eliminate the need for invasive surgery and radiation therapy, while more sensitive imaging strategies will allow for earlier detection and better prognosis (Ferrari, 2005, Nie et al., 2007, Takeda et al., 2008, Singhal et al., 2010). Thus, the development of highly sensitive and highly specific nanoparticle-based optical imaging platforms could have a revolutionary impact on prevention, diagnosis and treatment of cancer.

This review provides a comprehensive summary of recent progress in nanomedicine as it relates specifically to nanoparticles and anticancer drug delivery. Research into different nanoprobes for cancer detection/imaging will also be discussed. Lastly, the future of this growing and dynamic field and its potential impact on cancer treatment will be discussed.

Section snippets

Cancer treatment

The majority of anticancer therapeutics are water insoluble and need to be dissolved in an organic solvent in order to be administered as an injectable solution (Kwon, 2003). These organic solvents are toxic and have their own side effects. The low molecular weight of anticancer drugs results in rapid excretion and a poor therapeutic index (Walko & McLeod, 2009), requiring the administration of escalating doses to the cancer patient and therefore increasing the incidence of cytotoxicity and

Cancer detection

Because of their unique physical and chemical properties, nanoparticles have also been explored as synthetic scaffolds for imaging probes used in the detection and monitoring of cancer and cancer treatment. The same characteristics that make nanoparticles such an excellent platform for drug delivery, namely tunable surface properties, which enable the synthesis of aqueous injectable solutions and the development of passive or active targeted systems, also make them a sought-after platform for

Conclusion

Nanotechnology is generally viewed as one of the greatest engineering advances since the industrial revolution, and has the potential to significantly impact contemporary science and medicine. The rapid emergence of cutting edge applications of nanotechnology in the field of medicine is evidenced by the fact that this sector is growing by more than 17% annually and is expected to reach ~$53 billion by 2011 (http://www.nanotechwire.com) (Fredonia Group, 2007). According to US National Science

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