Targeted Drug Delivery for the Treatment of Blood Cancers

Abstract

Blood cancers are a type of liquid tumor which means cancer is present in the body fluid. Multiple myeloma, leukemia, and lymphoma are the three common types of blood cancers. Chemotherapy is the major therapy of blood cancers by systemic administration of anticancer agents into the blood. However, a high incidence of relapse often happens, due to the low efficiency of the anticancer agents that accumulate in the tumor site, and therefore lead to a low survival rate of patients. This indicates an urgent need for a targeted drug delivery system to improve the safety and efficacy of therapeutics for blood cancers. In this review, we describe the current targeting strategies for blood cancers and recently investigated and approved drug delivery system formulations for blood cancers. In addition, we also discuss current challenges in the application of drug delivery systems for treating blood cancers.

Keywords: blood cancers; drug delivery; nanomedicines.

Figure 1

Targeting the bone surface-mediated bone marrow: (a) Characterization of the bone-targeting delivery system in vitro and in vivo. Chemical structure of icaritin (ICT); (b) the morphology of Asp8-liposome-icaritin taken by cryo-transmission electron microscope (Cryo-TEM) (scale bar = 100 nm, magnification = 10⁵×); (c) localization of fluorescent-labeled liposome delivery system with or without Asp8 targeting peptide in mice by optical imaging IVIS analysis, 72 h after administration; (d) a schematic diagram to illustrate the experimental design for targeted delivery of antagomir-132 to specifically decrease miRNA-132-3p levels in bone; (e) a schematic diagram to illustrate how antagomir-132 is selectively delivered to bone formation region by (AspSerSer)₆; (f) analysis of miRNA-132-3p expression in the femur bone tissues of mice after hindlimb unloading for 21 days. BL—baseline group, mice were euthanatized and sampled at the beginning of experiment; CON—control group mice were raised in normal conditions during the experiment; HU—hindlimb unloading group, mice were submitted to a hindlimb unloading experiment; HU + Mock—hindlimb unloading plus (AspSerSer)₆-liposome injection group, mice were injected with the (AspSerSer)₆-liposome before HU; HU + antagomir-NC—hindlimb unloading plus (AspSerSer)₆-liposome-antagomir-NC injection group, mice were injected with the (AspSerSer)₆-liposome-antagomir-NC before HU; HU + antagomir-132—hindlimb unloading plus (AspSerSer)₆-liposome-antagomir-132 injection group, mice were injected with the (AspSerSer)₆-liposome-antagomir-132 before HU. Values are shown as mean ± SD, n  =  6. * p  <  0.05. NS, not significant. (a–c) Adapted with permission from [17] and (d–f) adapted with permission from [19].

Figure 2

Active targeting strategy by peptide or antibody mediated nanomedicines: (a) Illustration of PEGylated non-targeted liposomal carfilzomib nanoparticles (NP[Carf], left) and VLA-4 targeted liposomal carfilzomib nanoparticles (TNP[Carf], right); (b) liposomal carfilzomib nanoparticles preferentially accumulate in the tumor, inhibit tumor growth, and reduce systemic toxicities in vivo. Tumor bearing SCID mice were injected intravenously on Days 1, 2, 8, and 9 with NP[Carf], TNP[Carf], free carfilzomib, and PBS at a dose of 5 mg/kg carfilzomib equivalence. Tumor growth inhibition was measured via calipers; (c) in vivo images of near infrared dye loaded targeted nanoparticles in tumor bearing mice. Images were taken for all mice at t = 2, 6, and 24 h using non-invasive methods. The representative images show the accumulation of the nanoparticles in the tumor (white arrow) over time; (d,e) in vivo efficacy of CD38pep- and CD138pep-targeted nanoparticles loaded with prodrug doxorubicin. Nanoparticles targeted with CD38pep or CD138pep were prepared loaded with a doxorubicin prodrug and their in vivo efficacy was tested against that of free doxorubicin in a subcutaneous xenograft mouse model. Mice were injected with H929 cells and tumors were allowed to grow to a predetermined size before i.v. injection of nanoparticle formulations began on Day 1. Mice were injected with 3 mg/kg of doxorubicin or nanoparticle prodrug equivalent on Days 1, 3, 5, 7, and 9. Tumor volume (d) and survival (e) were tracked with mice being killed when tumor volume grew too large or mouse weight was too low. n = 6 for all groups and data represent means (± s.e.m.). (a–c) Adapted with permission from [26] and (d–e) adapted with permission from [28]).