Polymeric micelles with photo-activated proton release behavior for enhanced tumor extracellular pH targeting and drug release

The extracellular pH (6.5-7.2) of most tumors varies only slightly from those of the normal tissues and blood (pH 7.4). For enhanced tumor extracellular pH targeting, Polymeric micelles (PM) based on 1-pyrenemethanol-modified carboxymethyl chitosan conjugate with succinyl linkage (PCMC) were constructed to regulate tumor extracellular pH. TEM observation showed that the micelles had a core-shell structure with an average diameter of 210 +/- 10.7 nm. Dynamic light scattering studies indicated that the micelles had good in vitro stability. However, upon exposure to UV stimuli, the micelles were disrupted and accompanied by proton release, which could trigger the aggregation of non-irradiated micelles at pH 6.0. The UV intensity and irradiation time showed an obvious influence on the proton release. The proton release mechanism may be attributed to the photosolvolysis of the ester bond linked to the pyrenemethyl groups in the polymeric side chains, which was proved by UV-Vis and H-1 NMR. Paclitaxel (PTX) was entrapped into the core of micelles as a model drug, which only showed an accumulative release rate of 3.5% within 12 h at pH 7.4. However, at pH 6.8 with UV irradiation (365 nm, 500 mW cm(-2)) for 4 min and subsequently by mixing with an aliquot of non-irradiated drug loaded sample, an enhanced drug release and significant inhibition rate against HeLa cells were observed. The study provided a new strategy for the design of tumor extracellular pH targeted nanocarriers for drug delivery.