Is nanomedicine still promising?

A recent study by Mann et al. [1] published in Oncotarget exploits the use of aptamers as a targeting ligand to develop site-specific delivery of liposomal nanocarriers. It has already been 17 years, since an article titled 'Liposomes revisited' was published co-authored by Lasic and Papahadjopoulos [2]. In essence, this publication marked the launch of the first success story of nanomedicine into the clinic and the beginning of an entire field. However, this was not an accident. The successful development of sterically stabilized liposomes was the product of 30 years of intensive research, since Bangham first discovered in the early 1960s that phospholipids in water form a vesicle enclosed in a bilayered lipid membrane [3, 4]. Not surprisingly, a pubmed search of the word 'liposome' resulted in 14,858 articles published between 1965 and 1995. The focus of these studies ranged from the in vitro particle stability to the effect of size, lipid composition and polymer coating of liposomes on their blood circulation, intratumoral accumulation and anticancer activity [5-7]. Furthermore, stable encapsulation of doxorubicin into the liposome with negligible leakage of the drug in blood circulation was achieved with the remote loading method against an ammonium sulfate gradient [8]. And finally voilá: a PEGylated unilamellar liposome composed of rigid phosphatidylcholine and cholesterol with a diameter of about 100 nm displayed prolonged circulation time and as a result an increased intratumoral accumulation and antitumor activity [6, 7]. So, what is the advantage of a long-circulating nanoparticle over conventional chemotherapies? It was shown that the therapeutic index of chemotherapeutics can be substantially improved, since nanoparticle delivery systems exploit a feature of tumor microenvironment, the so-called 'Enhanced Permeability and Retention' (EPR) effect [9]. While potent chemotherapeutic drugs are available to oncologists, the systemic dose of these agents is constrained by normal tissue tolerance, since these agents are distributed within cancer and healthy tissues in a non-specific manner. On the other hand, liposomes improve the safety profile of drugs due to their localization with high specificity in solid tumors while reducing off-target delivery [10, 11]. This unique feature has led to the development of various nanoparticle delivery systems, which are under preclinical and clinical evaluation [12]. The question that emerges then is: Could this old dog learn new tricks? This was promptly answered as it was recognized that the key feature of nanoparticles is the ability to combine more than one function by enabling the …