Limits...
pH-responsive Virus-like Nanoparticles with Enhanced Tumour-targeting Ligands for Cancer Drug Delivery

View Article: PubMed Central - PubMed

ABSTRACT

Multifunctional nanocarriers harbouring specific targeting moieties and with pH-responsive properties offer great potential for targeted cancer therapy. Several synthetic drug carriers have been studied extensively as drug delivery systems but not much information is available on the application of virus-like nanoparticles (VLNPs) as multifunctional nanocarriers. Here, we describe the development of pH-responsive VLNPs, based on truncated hepatitis B virus core antigen (tHBcAg), displaying folic acid (FA) for controlled drug delivery. FA was conjugated to a pentadecapeptide containing nanoglue bound on tHBcAg nanoparticles to increase the specificity and efficacy of the drug delivery system. The tHBcAg nanoparticles loaded with doxorubicin (DOX) and polyacrylic acid (PAA) demonstrated a sustained drug release profile in vitro under tumour tissue conditions in a controlled manner and improved the uptake of DOX in colorectal cancer cells, leading to enhanced antitumour effects. This study demonstrated that DOX-PAA can be packaged into VLNPs without any modification of the DOX molecules, preserving the pharmacological activity of the loaded DOX. The nanoglue can easily be used to display a tumour-targeting molecule on the exterior surface of VLNPs and can bypass the laborious and time-consuming genetic engineering approaches.

No MeSH data available.


Packaging of doxorubicin by tHBcAg nanoparticles.(a) Sucrose density gradient ultracentrifugation of different tHBcAg nanoparticle packaging samples. tHBcAg nanoparticles containing doxorubicin (DOX) were separated by ultracentrifugation on sucrose gradients (8–40%). The total protein in each fraction (400 μL) was determined by a Bradford assay. Packaging of DOX with tHBcAg nanoparticles (tHBcAg-DOX), tHBcAg nanoparticles loaded with PAA-DOX (tHBcAg-PAA-DOX), and FA-conjugated tHBcAg nanoparticles using the nanoglue and loaded with PAA-DOX (FA-N-tHBcAg-PAA-DOX). tHBcAg nanoparticles (tHBcAg) were used as a negative control. (b) Electron micrographs of the tHBcAg nanoparticles from different packaging samples. The samples are labelled on top of the micrographs. All the samples assembled into spherical structures. White bars indicate 50 nm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5121657&req=5

f4: Packaging of doxorubicin by tHBcAg nanoparticles.(a) Sucrose density gradient ultracentrifugation of different tHBcAg nanoparticle packaging samples. tHBcAg nanoparticles containing doxorubicin (DOX) were separated by ultracentrifugation on sucrose gradients (8–40%). The total protein in each fraction (400 μL) was determined by a Bradford assay. Packaging of DOX with tHBcAg nanoparticles (tHBcAg-DOX), tHBcAg nanoparticles loaded with PAA-DOX (tHBcAg-PAA-DOX), and FA-conjugated tHBcAg nanoparticles using the nanoglue and loaded with PAA-DOX (FA-N-tHBcAg-PAA-DOX). tHBcAg nanoparticles (tHBcAg) were used as a negative control. (b) Electron micrographs of the tHBcAg nanoparticles from different packaging samples. The samples are labelled on top of the micrographs. All the samples assembled into spherical structures. White bars indicate 50 nm.

Mentions: The method of dissociation and association13 was used to package DOX and PAA inside the tHBcAg nanoparticles. Figure 4a shows the migration profiles of different packaging samples in a sucrose gradient. In the absence of cargo, the tHBcAg nanoparticles migrated into the gradient and accumulated in fractions 7–18. The migration profile is in accord with that reported by Tan et al.26. Packaging of DOX in the absence of PAA (tHBcAg-DOX) did not result in any differences in the migration profile of the nanoparticles compared with that of tHBcAg (Fig. 4a). This demonstrates that DOX alone cannot be packaged by tHBcAg nanoparticles. When PAA and DOX were loaded, the tHBcAg-PAA-DOX nanoparticles migrated faster in the gradient, and the peak shifted to a higher density, demonstrating the presence of denser nanoparticles (fractions 13–22).


pH-responsive Virus-like Nanoparticles with Enhanced Tumour-targeting Ligands for Cancer Drug Delivery
Packaging of doxorubicin by tHBcAg nanoparticles.(a) Sucrose density gradient ultracentrifugation of different tHBcAg nanoparticle packaging samples. tHBcAg nanoparticles containing doxorubicin (DOX) were separated by ultracentrifugation on sucrose gradients (8–40%). The total protein in each fraction (400 μL) was determined by a Bradford assay. Packaging of DOX with tHBcAg nanoparticles (tHBcAg-DOX), tHBcAg nanoparticles loaded with PAA-DOX (tHBcAg-PAA-DOX), and FA-conjugated tHBcAg nanoparticles using the nanoglue and loaded with PAA-DOX (FA-N-tHBcAg-PAA-DOX). tHBcAg nanoparticles (tHBcAg) were used as a negative control. (b) Electron micrographs of the tHBcAg nanoparticles from different packaging samples. The samples are labelled on top of the micrographs. All the samples assembled into spherical structures. White bars indicate 50 nm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121657&req=5

f4: Packaging of doxorubicin by tHBcAg nanoparticles.(a) Sucrose density gradient ultracentrifugation of different tHBcAg nanoparticle packaging samples. tHBcAg nanoparticles containing doxorubicin (DOX) were separated by ultracentrifugation on sucrose gradients (8–40%). The total protein in each fraction (400 μL) was determined by a Bradford assay. Packaging of DOX with tHBcAg nanoparticles (tHBcAg-DOX), tHBcAg nanoparticles loaded with PAA-DOX (tHBcAg-PAA-DOX), and FA-conjugated tHBcAg nanoparticles using the nanoglue and loaded with PAA-DOX (FA-N-tHBcAg-PAA-DOX). tHBcAg nanoparticles (tHBcAg) were used as a negative control. (b) Electron micrographs of the tHBcAg nanoparticles from different packaging samples. The samples are labelled on top of the micrographs. All the samples assembled into spherical structures. White bars indicate 50 nm.
Mentions: The method of dissociation and association13 was used to package DOX and PAA inside the tHBcAg nanoparticles. Figure 4a shows the migration profiles of different packaging samples in a sucrose gradient. In the absence of cargo, the tHBcAg nanoparticles migrated into the gradient and accumulated in fractions 7–18. The migration profile is in accord with that reported by Tan et al.26. Packaging of DOX in the absence of PAA (tHBcAg-DOX) did not result in any differences in the migration profile of the nanoparticles compared with that of tHBcAg (Fig. 4a). This demonstrates that DOX alone cannot be packaged by tHBcAg nanoparticles. When PAA and DOX were loaded, the tHBcAg-PAA-DOX nanoparticles migrated faster in the gradient, and the peak shifted to a higher density, demonstrating the presence of denser nanoparticles (fractions 13–22).

View Article: PubMed Central - PubMed

ABSTRACT

Multifunctional nanocarriers harbouring specific targeting moieties and with pH-responsive properties offer great potential for targeted cancer therapy. Several synthetic drug carriers have been studied extensively as drug delivery systems but not much information is available on the application of virus-like nanoparticles (VLNPs) as multifunctional nanocarriers. Here, we describe the development of pH-responsive VLNPs, based on truncated hepatitis B virus core antigen (tHBcAg), displaying folic acid (FA) for controlled drug delivery. FA was conjugated to a pentadecapeptide containing nanoglue bound on tHBcAg nanoparticles to increase the specificity and efficacy of the drug delivery system. The tHBcAg nanoparticles loaded with doxorubicin (DOX) and polyacrylic acid (PAA) demonstrated a sustained drug release profile in vitro under tumour tissue conditions in a controlled manner and improved the uptake of DOX in colorectal cancer cells, leading to enhanced antitumour effects. This study demonstrated that DOX-PAA can be packaged into VLNPs without any modification of the DOX molecules, preserving the pharmacological activity of the loaded DOX. The nanoglue can easily be used to display a tumour-targeting molecule on the exterior surface of VLNPs and can bypass the laborious and time-consuming genetic engineering approaches.

No MeSH data available.