Abstract
Upconversion nanoparticles (UCNP) with unique multi-photon excitation photo-luminescence properties have been extensively explored as novel contrast agents for low-background biomedical imaging. There is an increasing interest in employing UCNPs as carrier for drug delivery as these offers a unique opportunity to combine therapy and diagnostics in one platform (theranostics). In the present work, we report microwave-assisted synthesis of hexagonal NaYF4:Yb/Er UCNPs coated with porous silica and functionalized with amine (UCNP@mSiO2). The UCNP@mSiO2 were investigated for controlled delivery of a chemotherapeutic agent, doxorubicin (DOX, hydrophilic), and a chemosensitizing agent, curcumin (CCM, hydrophobic). The drug loading was relatively higher for DOX (17.4%), in comparison to CCM (8.1%). The cumulative drug release from DOX-loaded UCNP@mSiO2 were 30 and 41% at physiological (7.4) and tumoral (6.4) pH, following a pseudo Fickian release pattern, whereas the release from CCM-loaded UCNP@mSiO2 were 27 and 50% at pH 7.4 and 6.4, following a non-Fickian and pseudo-Fickian release patterns, respectively. Both DOX and CCM-loaded UCNP@mSiO2 exhibited pH-dependent controlled drug delivery but the effect was more pronounced for CCM, the hydrophobic chemosensitizer. Cell viability assay using HeLa cells showed that DOX-loaded UCNP@mSiO2 inhibit cell growth in a dose-dependent manner, similar to free DOX, but the cell inhibition activity of free CCM was lower than CCM passively entrapped in UCNP@mSiO2. Confocal microscopy studies revealed cell uptake of both the drug by HeLa cells. Thus, UCNP@mSiO2 exhibited the unique capability to deliver hydrophilic and hydrophobic drugs, individually. UCNP@mSiO2 carrier, equipped with theranostic capabilities, may potentially be used for pH-responsive release of chemotherapeutic agents in cancer environment.
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