Covalent attachment of Mn-porphyrin onto doxorubicin-loaded poly(lactic acid) nanoparticles for potential magnetic resonance imaging and pH-sensitive drug delivery

Abstract

In this paper, theranostic nanoparticles (MnP-DOX NPs) were fabricated by conjugating Mn-porphyrin onto the surface of doxorubicin (DOX)-loaded poly(lactic acid) (PLA) nanoparticles (DOX NPs) for potential T1 magnetic resonance imaging and pH-sensitive drug delivery. An in vitro drug release study showed that the release rate of DOX from MnP-DOX NPs was slow at neutral pH but accelerated significantly in acidic conditions. It was found that MnP-DOX NPs could be easily internalized by HeLa cells and effectively suppressed the growth of HeLa cells and HT-29 cells due to the accelerated drug release in acidic lysosomal compartments. Magnetic resonance imaging (MRI) scanning analysis demonstrated that MnP-DOX NPs had much higher longitudinal relaxivity in water (r1 value of 27.8mM−1s−1 of Mn3+) than Mn-porphyrin (Mn(III)TPPS3NH2; r1 value of 6.70mM−1s−1 of Mn3+), behaving as an excellent contrast agent for T1-weighted MRI both in vitro and in vivo. In summary, such a smart and promising nanoplatform integrates multiple capabilities for effective cancer diagnosis and therapy.