Multifunctional micellar nanomedicine for cancer therapy

Abstract

Polymeric micelles are supramolecular, core-shell nanoparticles that offer considerable advantages for cancer diagnosis and therapy. Their relatively small size (10-100 nm), ability to solubilize hydrophobic drugs as well as imaging agents, and improved pharmacokinetics provide a useful bioengineering platform for cancer applications. Several polymeric micelle formulations are currently undergoing phase I/II clinical trials, which have shown improved antitumor efficacy and reduced systemic toxicity. This minireview will focus on recent advancements in the multifunctional design of micellar nanomedicine with tumor targeting, stimulated drug release, and cancer imaging capabilities. Such functionalization strategies result in enhanced micellar accumulation at tumor sites, higher drug bioavailability, as well as improved tumor diagnosis and visualization of therapy. Ultimately, integrated nanotherapeutic systems (e.g., theranostic nanomedicine) may prove essential to address the challenges of tumor heterogeneity and adaptive resistance to achieve efficacious treatment of cancer.

Figure 1

Schematic of the core-shell architecture of a polymer micelle and its dimensions.

Figure 2

Multifunctional design of a micelle nanomedicine platform with cancer targeting, imaging, and controlled release properties.

Figure 3

(A) Schematic of a multifunctional polymeric micelle. (B-C) Pre- and post-contrast coronal images of tumor-bearing mice by T₂-weighted imaging (TR/TE = 4s/40 ms), respectively. (D-E) Bioluminescence imaging of mouse bearing luciferase-transfected H1299 xenograft at day 0 and 7, respectively. DOX-loaded, 16% cRGD-micelles were injected via tail vein at day 0 and 3 (4 mg/kg DOX dose each time). (F) Antitumor efficacy data for PBS control, DOXO-SPIO micelles with 0 and 16% surface density of cRGD in subcutaneous A549 tumor xenografts in nude mice. Each data point is averaged from 3 animals.