Although
smart polymer micelles able to respond to the tumor acid
microenvironment are potential anticancer drug carriers, fruitful
clinical application of these carriers is inadequate. For the purpose
of finding the origin of the unsatisfactory therapeutic efficacy of
pH-sensitive drug carriers with tertiary amine groups, we newly designed
and synthesized poly{α-[4-(diethylamino)methyl-1,2,3-triazol]-caprolactone-co-caprolactone}-b-poly(2-methacryloyloxyethyl
phosphorylcholine) (PDCL-PMPC), a biomimetic phosphorylcholine polymer
with pH-ensitive groups. PDCL-PMPC self-assembles into small and uniform
micelles as its counterpart poly(caprolactone)-b-poly(2-methacryloyloxyethyl
phosphorylcholine) (PCL-PMPC) without pH-sensitive groups. The in
vitro and in vivo properties of PDCL-PMPC and PCL-PMPC micelles are
investigated in detail. PDCL-PMPC micelles display obvious pH sensitivity
by micelle change and fast drug release at pH 5, but the insensitive
micelles do not. The internalization of PDCL-PMPC micelles by tumor
cells is stronger than that of PCL-PMPC micelles. However, in comparison
with the insensitive micelles, the pH-sensitive micelles present much
shorter blood circulation time in pharmacokinetics and demonstrate
worse accumulation in the tumor site in vivo study. As a result, DOX
loaded PCL-PMPC micelles demonstrate much better antitumor efficiency
than pH-sensitive micelles. Furthermore, DOX loaded PCL-PMPC micelles
show similar therapeutic efficacy to DOX·HCl but with considerably
lower side effects.