Limits...
Fabrication of functional hollow microspheres constructed from MOF shells: Promising drug delivery systems with high loading capacity and targeted transport

View Article: PubMed Central - PubMed

ABSTRACT

An advanced multifunctional, hollow metal-organic framework (MOF) drug delivery system with a high drug loading level and targeted delivery was designed and fabricated for the first time and applied to inhibit tumour cell growth. This hollow MOF targeting drug delivery system was prepared via a simple post-synthetic surface modification procedure, starting from hollow ZIF-8 successfully obtained for the first time via a mild phase transformation under solvothermal conditions. As a result, the hollow ZIF-8 exhibits a higher loading capacity for the model anticancer drug 5-fluorouracil (5-FU). Subsequently, 5-FU-loaded ZIF-8 was encapsulated into polymer layers (FA-CHI-5-FAM) with three components: a chitosan (CHI) backbone, the imaging agent 5-carboxyfluorescein (5-FAM), and the targeting reagent folic acid (FA). Thus, an advanced drug delivery system, ZIF-8/5-FU@FA-CHI-5-FAM, was fabricated. A cell imaging assay demonstrated that ZIF-8/5-FU@FA-CHI-5-FAM could target and be taken up by MGC-803 cells. Furthermore, the as-prepared ZIF-8/5-FU@FA-CHI-5-FAM exhibited stronger cell growth inhibitory effects on MGC-803 cells because of the release of 5-FU, as confirmed by a cell viability assay. In addition, a drug release experiment in vitro indicated that ZIF-8/5-FU@FA-CHI-5-FAM exhibited high loading capacity (51%) and a sustained drug release behaviour. Therefore, ZIF-8/5-FU@FA-CHI-5-FAM could provide targeted drug transportation, imaging tracking and localized sustained release.

No MeSH data available.


The excitation (A) and emission (B) spectra of 5-FAM and the excitation (C) and emission (D) spectra of ZIF-8/5-FU@FA-CHI-5-FAM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5120282&req=5

f6: The excitation (A) and emission (B) spectra of 5-FAM and the excitation (C) and emission (D) spectra of ZIF-8/5-FU@FA-CHI-5-FAM.

Mentions: The photoluminescence properties of 5-FAM and ZIF-8/5-FU@FA-CHI-5-FAM are shown in Fig. 6. The luminescence spectra of ZIF-8/5-FU@FA-CHI-5-FAM are similar to those of 5-FAM, suggesting that the luminescent property of ZIF-8/5-FU@FA-CHI-5-FAM is mostly attributable to the emission of the 5-FAM. The emission spectra of 5-FAM, monitored under the characteristic excitation (437 nm) of the 5-FAM, exhibit a broad band with a maximum at 518 nm. Obviously, ZIF-8/5-FU@FA-CHI-5-FAM displays very strong emission with the maxima at 520 nm when excited at 441 nm, which is similar to the 5-FAM. These emission spectra indicate that the ZIF-8/5-FU@FA-CHI-5-FAM belongs to the class of luminescence materials with broad emission bands; in this case, the emission bands extend to the visible-light region and can already fulfill the requirements of bioimaging, as demonstrated in Fig. 7. For effective drug-based cancer treatment, the drug must be accumulated within tumours specifically. FA is considered one of the most promising targeting reagents for cancerous cells. Here, we evaluate the targeting efficacy of FA by incubating ZIF-8/5-FU@FA-CHI-5-FAM and ZIF-8/5-FU@CHI-5-FAM with FA-positive MGC-803 cells and FA-negative HASMC cells for 2 h. Our cellular uptake imaging in Fig. 7 clearly shows that the green fluorescence in MGC-803 cells incubated with ZIF-8/5-FU@FA-CHI-5-FAM is strong. By contrast, the green fluorescence in MGC-803 cells incubated with ZIF-8/5-FU@CHI-5-FAM and HASMC cells incubated with ZIF-8/5-FU@FA-CHI-5-FAM is very weak. In other words, ZIF-8/5-FU@FA-CHI-5-FAM (Fig. 7A) entered MGC-803 cells much more easily compared to free ZIF-8/5-FU@CHI-5-FAM (Fig. 7B). While, ZIF-8/5-FU@FA-CHI-5-FAM can hardly be taken on by the HASMC cells (Fig. 7C), indicating that ZIF-8/5-FU@FA-CHI-5-FAM is capable of cancer targeting.


Fabrication of functional hollow microspheres constructed from MOF shells: Promising drug delivery systems with high loading capacity and targeted transport
The excitation (A) and emission (B) spectra of 5-FAM and the excitation (C) and emission (D) spectra of ZIF-8/5-FU@FA-CHI-5-FAM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120282&req=5

f6: The excitation (A) and emission (B) spectra of 5-FAM and the excitation (C) and emission (D) spectra of ZIF-8/5-FU@FA-CHI-5-FAM.
Mentions: The photoluminescence properties of 5-FAM and ZIF-8/5-FU@FA-CHI-5-FAM are shown in Fig. 6. The luminescence spectra of ZIF-8/5-FU@FA-CHI-5-FAM are similar to those of 5-FAM, suggesting that the luminescent property of ZIF-8/5-FU@FA-CHI-5-FAM is mostly attributable to the emission of the 5-FAM. The emission spectra of 5-FAM, monitored under the characteristic excitation (437 nm) of the 5-FAM, exhibit a broad band with a maximum at 518 nm. Obviously, ZIF-8/5-FU@FA-CHI-5-FAM displays very strong emission with the maxima at 520 nm when excited at 441 nm, which is similar to the 5-FAM. These emission spectra indicate that the ZIF-8/5-FU@FA-CHI-5-FAM belongs to the class of luminescence materials with broad emission bands; in this case, the emission bands extend to the visible-light region and can already fulfill the requirements of bioimaging, as demonstrated in Fig. 7. For effective drug-based cancer treatment, the drug must be accumulated within tumours specifically. FA is considered one of the most promising targeting reagents for cancerous cells. Here, we evaluate the targeting efficacy of FA by incubating ZIF-8/5-FU@FA-CHI-5-FAM and ZIF-8/5-FU@CHI-5-FAM with FA-positive MGC-803 cells and FA-negative HASMC cells for 2 h. Our cellular uptake imaging in Fig. 7 clearly shows that the green fluorescence in MGC-803 cells incubated with ZIF-8/5-FU@FA-CHI-5-FAM is strong. By contrast, the green fluorescence in MGC-803 cells incubated with ZIF-8/5-FU@CHI-5-FAM and HASMC cells incubated with ZIF-8/5-FU@FA-CHI-5-FAM is very weak. In other words, ZIF-8/5-FU@FA-CHI-5-FAM (Fig. 7A) entered MGC-803 cells much more easily compared to free ZIF-8/5-FU@CHI-5-FAM (Fig. 7B). While, ZIF-8/5-FU@FA-CHI-5-FAM can hardly be taken on by the HASMC cells (Fig. 7C), indicating that ZIF-8/5-FU@FA-CHI-5-FAM is capable of cancer targeting.

View Article: PubMed Central - PubMed

ABSTRACT

An advanced multifunctional, hollow metal-organic framework (MOF) drug delivery system with a high drug loading level and targeted delivery was designed and fabricated for the first time and applied to inhibit tumour cell growth. This hollow MOF targeting drug delivery system was prepared via a simple post-synthetic surface modification procedure, starting from hollow ZIF-8 successfully obtained for the first time via a mild phase transformation under solvothermal conditions. As a result, the hollow ZIF-8 exhibits a higher loading capacity for the model anticancer drug 5-fluorouracil (5-FU). Subsequently, 5-FU-loaded ZIF-8 was encapsulated into polymer layers (FA-CHI-5-FAM) with three components: a chitosan (CHI) backbone, the imaging agent 5-carboxyfluorescein (5-FAM), and the targeting reagent folic acid (FA). Thus, an advanced drug delivery system, ZIF-8/5-FU@FA-CHI-5-FAM, was fabricated. A cell imaging assay demonstrated that ZIF-8/5-FU@FA-CHI-5-FAM could target and be taken up by MGC-803 cells. Furthermore, the as-prepared ZIF-8/5-FU@FA-CHI-5-FAM exhibited stronger cell growth inhibitory effects on MGC-803 cells because of the release of 5-FU, as confirmed by a cell viability assay. In addition, a drug release experiment in vitro indicated that ZIF-8/5-FU@FA-CHI-5-FAM exhibited high loading capacity (51%) and a sustained drug release behaviour. Therefore, ZIF-8/5-FU@FA-CHI-5-FAM could provide targeted drug transportation, imaging tracking and localized sustained release.

No MeSH data available.