Recent progress in tumor pH targeting nanotechnology - PubMed (original) (raw)

Review

Recent progress in tumor pH targeting nanotechnology

Eun Seong Lee et al. J Control Release. 2008.

Abstract

pH-sensitive polymeric micelles and nanogels have recently been developed to target slightly acidic extracellular pH environment of solid tumors. The pH targeting approach is regarded as a more general strategy than conventional specific tumor cell surface targeting approaches, because the acidic tumor microclimate is most common in solid tumors. When nanosystems are combined with triggered release mechanisms by endosomal or lysosomal acidity plus endosomolytic capability, the nanocarriers demonstrated to overcome multidrug resistance of various tumors. This review highlights recent progress of the pH-sensitive nanotechnology developed in Bae research group.

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Figures

Figure 1

Figure 1

Mouse dorsal skin fold window chamber made of two symmetrical titanium frames. Tumor piece was inoculated into nu/nu mouse window chamber (A). After implanting MDA 213 breast cancer tumor piece, tumor blood vessels were growing in the window chamber Day 1 (B) and Day 15 (C). Normal blood vessel images after IV injection of DOX loaded pH-sensitive micelles (polyHis (Mw 5,000)-_b_-PEG (Mw 3,000)) 5 min and 60 min were shown in (D) and (E), respectively. The tumor blood vessels after i.v. injection of DOX loaded pH-insensitive and pH-sensitive micelles at the time course for 60 min were present in row (F) and row (G). The bright color is from DOX fluorescence. Reproduced with permission from reference [64].

Figure 2

Figure 2

Schematic concept for a proposed drug delivery system: the carrier system consists of two components, poly(L-lactic acid)-_b_-PEG-TAT micelles and pH-sensitive poly(methacryloyl sulfadimethoxine-_b_-PEG. a) At normal blood pH, polysulfonamide is negatively charged, and when mixed with TAT, polysulfonamide shields the TAT by electrostatic interaction. Only PEG is exposed to the outside which could make the carrier long circulating; b) when the system experiences a decrease in pH (near tumor) polysulfonamide loses charge and detaches, exposing TAT for interaction with tumor cells. Reproduced with permission from reference [68].

Figure 3

Figure 3

Schematic diagram depicting the central concept of pH induced biotin repositioning on the micelle. While above pH 7.0, biotin that is anchored on the micelle core via a pH-sensitive molecular chain actuator (polyHis) is shielded by PEG shell of the micelle; biotin is exposed on the micelle surface (6.5 < pH < 7.0) and can interact with cells, which facilitates biotin receptor-mediated endocytosis. When the pH is further lowered (pH < 6.5), the micelle destabilizes, resulting in enhanced drug release and disrupting cell membranes such as endosomal membrane. Reproduced with permission from reference [60].

Figure 4

Figure 4

pH-dependent cellular uptake of the micelles in cultured MCF-7 tumor cells caused by TAT exposure: pH 7.4 (•), pH 7.0 (■), pH 6.8 (▲). Particle size and size distributions of micelle suspensions (in PBS) at pH 7.4 were measured by dynamic light scattering. Each data point represents an average with standard deviation (n=3). Reproduced with permission from reference [45].

Figure 5

Figure 5

Schematic presentation of the virus-like nanogel. See the text for more details.

Figure 6

Figure 6

Release rate of DOX from DOX-loaded virus-like infectious nanogels. 150 μg of DOX was encapsulated into 1 mg of DOX-loaded VM-nanogels. The pH of the solution is stepwise adjusted to pH 7.4, pH 6.8 and pH 6.4 at one-hour intervals. Each data point represents an average with standard deviation (n=3). Reproduced with permission from reference [46].

Figure 7

Figure 7

Virus-like nanogels infect cells selectively depending on specific interactions, kill the host cells, and migrate to neighboring cells as virus does to repeat the cycle.

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