研究目的
Investigating the therapeutic effects of a specific herbal medicine on a particular disease.
研究成果
In summary, we have fabricated hexagonal phase NaYF4:Yb/Er upconversion nanoparticles (UCNPs) and amine functionalized porous silica (mSiO2)-coated NaYF4: Yb/Er upconversion nanoparticles (UCNP@mSiO2). Their hexagonal phase structures were confirmed using powder XRD, whereas the particle size, porous coating, and surface morphology were studied using TEM and SEM. Photoluminescence measurements revealed two emission peaks in visible region, indicating strong up conversion capabilities, and both peaks were characteristic of electronic transitions associated with Er3+ions. The UCNP@mSiO2 were investigated for controlled delivery of DOX (hydrophilic) and CCM (hydrophobic) drugs. The UCNP@mSiO2 exhibited higher drug loading for DOX than CCM, and both DOX and CCM-loaded UCNP@mSiO2 showed pH-dependent controlled drug delivery, with percentage of drug released being higher at tumoral pH (6.4), in comparison to physiological pH (7.4). Interestingly, the cumulative drug release and pH-dependence was much more prominent in case of CCM. The cell viability assay against HeLa cells indicated that DOX-loaded UCNP@mSiO2 inhibited cell growth in a dose-dependent manner, similar to free DOX. However, the cell inhibition activity of CCM was subdued on account of poor dissolution in aqueous media but the activity was restored upon passive entrapment in UCNP@mSiO2. Both loaded drugs showed uptake by HeLa cells, illustrating effective internalization. Overall, the results indicate possible use of UCNP@mSiO2 in pH-responsive cancer drug delivery applications. Owing to the up conversion characteristics, UCNP@mSiO2 also offers the advantage of real time monitoring of the intratumoral fate of drug payloads, a potential theranostic application.
研究不足
The technical and application constraints of the experiments, as well as potential areas for optimization.
1：Experimental Design and Method Selection
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).
2：Sample Selection and Data Sources
Yttriumtrichloridehexahydrate (YCl3.6H2O), ytterbiumtrichloridehexahydrate (YbCl3.6H2O), erbiumtrichloridehexahydrate (ErCl3.6H2O), sodium hydroxide (NaOH), ammonium fluoride (NH4F), ethanol, acetic acid, ammonium hydroxide (NH4OH), tetraethyl orthosilicate (TEOS),(3-aminopropyl)triethoxysilane (APTES) and TritonX-100 were purchased from Sigma Aldrich, India. All chemicals were used as received without further purification. Milli-Q water (18.2 MΩ-cm) was used for all experiments.
3：List of Experimental Equipment and Materials
Anton Paar – Multiwave PRO-microwave synthesizer, Rigaku Smart Lab 9 KW powder X-ray diffractometer (PXRD), transmission electron microscopy (TEM), FEI Tecnai G2 20 S-twin microscope operating at 200 kV, Agilent K8002AA Carry 660 instrument, Quantachrome Instruments, Autosorb-IQ volumetric adsorption analyzer, Zetasizer Nano ZS (Malvern Instrument), Cary eclipse fluorescence spectrophotometer equipped with an excitation source of 980 nm laser diode (CW, 500 mW).
4：Experimental Procedures and Operational Workflow
Yb, Er doped NaYF4 nanophosphors were prepared in ethanol and acetic acid mixture using a microwave-aided method. Porous silica coating on UCNP was carried out according to a previously reported approach, with few modifications. The in vitro drug loading and release studies were carried out using porous silica-coated NaYF4:Yb/Er (UCNP@mSiO2) at physiological (7.4) and tumoral (6.4) pHs. Both DOX and CCM were used in these studies.
5：Data Analysis Methods
The drug release data were fitted onto different release kinetic models and the most probable release kinetic model was found to be Korsemeyer-Peppas model.
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