Nanocarriers as Magic Bullets in the Treatment of Leukemia

Abstract

Leukemia is a type of hematopoietic stem/progenitor cell malignancy characterized by the accumulation of immature cells in the blood and bone marrow. Treatment strategies mainly rely on the administration of chemotherapeutic agents, which, unfortunately, are known for their high toxicity and side effects. The concept of targeted therapy as magic bullet was introduced by Paul Erlich about 100 years ago, to inspire new therapies able to tackle the disadvantages of chemotherapeutic agents. Currently, nanoparticles are considered viable options in the treatment of different types of cancer, including leukemia. The main advantages associated with the use of these nanocarriers summarized as follows: i) they may be designed to target leukemic cells selectively; ii) they invariably enhance bioavailability and blood circulation half-life; iii) their mode of action is expected to reduce side effects. FDA approval of many nanocarriers for treatment of relapsed or refractory leukemia and the desired results extend their application in clinics. In the present review, different types of nanocarriers, their capability in targeting leukemic cells, and the latest preclinical and clinical data are discussed.

Keywords: ALL; AML; CLL; CML; leukemia; liposome; nanocarrier; nanoparticle; nanosystem; targeted therapy.

Figure 1

Schematic representation of the different types of liposomal drug delivery systems. (A) Conventional liposome: liposome composed of a lipid bilayer of anionic, cationic or neutral phospholipids and cholesterol. Drugs can be incorporated both in the bilayer (hydrophobic drugs) and in the aqueous core (hydrophilic drugs). (B) PEGylated liposomes: lipid bilayer endowed with a PEGylated phospholipid to make the nanosystem stealth and sterically stable. (C) Ligand-targeted liposome—Liposomes can be used for specific targeting by attaching ligands (e.g., antibodies, peptides, and carbohydrates) to its surface or to the terminal end of the attached PEG chains. (D) Theranostic liposome—A lipid bilayer bearing at the same time an imaging and a therapeutic agent. A targeting vector can also be introduced. Reproduced with permission from [23], licensed under CC BY.

Figure 2

Schematic representation of (A) normal micelles and (B) inverted micelles. Adapted from [38] (published by MDPI), licensed under CC BY.

Figure 3

Main types of inorganic nanoparticles: (A) silica nanoparticles, (B) iron oxide nanoparticles, (C) gold nanoparticles, (D) quantum DOTs. Adapted from [63].

Figure 4

Schematic representation of the EPR effect. Reproduced with permission from [87] (published by MDPI), licensed under CC BY 3.0.

Figure 5

Spheroid and granular structure of a DepoFoam™ particle. Reproduced with permission from [26] (published by MDPI), licened under CC BY.