Polymeric micelles: nanocarriers for cancer-targeted drug delivery

Abstract

Polymeric micelles represent an effective delivery system for poorly water-soluble anticancer drugs. With small size (10-100 nm) and hydrophilic shell of PEG, polymeric micelles exhibit prolonged circulation time in the blood and enhanced tumor accumulation. In this review, the importance of rational design was highlighted by summarizing the recent progress on the development of micellar formulations. Emphasis is placed on the new strategies to enhance the drug/carrier interaction for improved drug-loading capacity. In addition, the micelle-forming drug-polymer conjugates are also discussed which have both drug-loading function and antitumor activity.

Fig. 1

Structure of PEG5000-Lys-(α-Fmoc-ε-oleoyl lysine)₂ and the postulated modes of carrier/drug and carrier/carrier interactions. Taken with permission from (53)

Fig. 2

Enhanced antitumor activity of PTX formulated in PEG_5K-VE₂ micelles. BALB/c mice were inoculated s.c. with 4T1.2 cells (2 × 10⁵ cells/mouse). Five days later, mice received various treatments on days 1, 3, 5, 9, 12, and tumor growth was monitored and plotted as relative tumor volume (mm³). P < 0.02 (PEG_5K-VE₂/PTX vs. Taxol, PEG_2K-VE/PTX or PEG_2K-VE₂/PTX). N = 5. Taken with permission from (80)

Fig. 3

Chemical structures of vitamin E (a), embelin (b) and FTS (c)

Fig. 4

In vivo NIRF imaging over time as indicated in prostate cancer. PC-3 xenograft-bearing mice at 2, 24, 48 h following i.v. injection of PEG_5K-EB₂ micelles co-loaded with PTX and DiD. Taken with permission from (94)

Fig. 5

Effects of FTS, PEG_5K-FTS₂ (L), and PEG_5K-FTS₂ (S) on total Ras expression by western blot analysis. Cells grown in medium containing 5% FBS were treated with 0.1% DMSO (control), PEG_5K-FTS₂ with liable linkage (L), PEG_5K-FTS₂ with stable linkage (S), and free FTS (at a FTS concentration of 10 μM), respectively, for 48 h. Total cell lysate was subjected to western blot analysis. Anti-Ras antibody was used to determine the total Ras levels in the cells. Taken with permission from (104)