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. 2017 Nov;24(1):681-691.
doi: 10.1080/10717544.2017.1309475.

Polydopamine and peptide decorated doxorubicin-loaded mesoporous silica nanoparticles as a targeted drug delivery system for bladder cancer therapy

Yi Wei  1 , Li Gao  1 , Lu Wang  2 , Lin Shi  3 , Erdong Wei  1 , Baotong Zhou  1 , Li Zhou  1 , Bo Ge  1
Affiliations

Polydopamine and peptide decorated doxorubicin-loaded mesoporous silica nanoparticles as a targeted drug delivery system for bladder cancer therapy

Yi Wei et al. Drug Deliv. 2017 Nov.

Abstract

We reported a simple polydopamine (PDA)-based surface modification method to prepare novel targeted doxorubicin-loaded mesoporous silica nanoparticles and peptide CSNRDARRC conjugation (DOX-loaded MSNs@PDA-PEP) for enhancing the therapeutic effects on bladder cancer. Drug-loaded NPs were characterized in terms of size, size distribution, zeta potential, transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) surface area and drug loading content. In vitro drug release indicated that DOX-loaded MSNs@PDA and MSNs@PDA-PEP had similar release kinetic profiles of DOX. The PDA coating well controlled DOX release and was highly sensitive to pH value. Confocal laser scanning microscopy (CLSM) showed that drug-loaded MSNs could be internalized by human bladder cancer cell line HT-1376, and DOX-loaded MSNs@PDA-PEP had the highest cellular uptake efficiency due to ligand-receptor recognition. The antitumor effects of DOX-loaded nanoparticles were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that targeted nanocarriers DOX-loaded MSNs@PDA-PEP were significantly superior to free DOX and DOX-loaded MSNs@PDA. The novel DOX-loaded MSNs@PDA-PEP, which specifically recognized HT-1376 cells, can be used as a potential targeted drug delivery system for bladder cancer therapy.

Keywords: Drug delivery; bladder cancer; mesoporous silica; polydopamine; targeted therapy.

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Conflict of interest statement

The authors report no conflicts of interest in this work. The authors alone are responsible for the content and writing of the paper.

This work was supported by Innovation Project of Guangxi Graduate Education (YCSZ2015219), Guangxi Natural Science Foundation (No. 2016GXNSFAA380305) and Guilin Scientific Research and Technology Development Project (No. 2016012706-15).

Figures

Scheme 1.
Scheme 1.
Schematic representation of the preparation techniques of DOX-loaded MSNs@PDA-PEP.
Figure 1.
Figure 1.
(A) TEM images and (B) DLS size distribution of MSNs, MSNs@PDA and MSNs@PDA-PEP.
Figure 2.
Figure 2.
(A) TGA curves and (B) FT-IR spectra of MSNs, MSNs@PDA and MSNs@PDA-PEP.
Figure 3.
Figure 3.
XPS spectra of MSNs, MSNs@PDA and MSNs@PDA-PEP. (A) Wide scan; (B) narrow scan for N1s peaks.
Figure 4.
Figure 4.
(A) In vitro drug release kinetic profiles of (A) DOX-loaded MSNs; (B) DOX-loaded MSNs@PDA; (C) DOX-loaded MSNs@PDA-PEP at different pH values.
Figure 5.
Figure 5.
(A) CLSM images of HT-1376 cells incubated with free DOX, DOX-loaded MSNs@PDA and DOX-loaded MSNs@PDA-PEP for 2 h. The cells were stained by DAPI (blue) and drug DOX was red.
Figure 6.
Figure 6.
Cellular uptake efficiencies of DOX-loaded MSNs@PDA and DOX-loaded MSNs@PDA-PEP at different drug concentrations (n =3). *p < 0.05; **p < 0.01.
Figure 7.
Figure 7.
Viability of HT-1376 cells incubated with free DOX, DOX-loaded MSNs, DOX-loaded MSNs@PDA and DOX-loaded MSNs@PDA-PEP at the same drug concentrations: (A) 24 h; (B) 48 h (n =3). *p < 0.05; **p < 0.01; ***p < 0.001.
Figure 8.
Figure 8.
(A) Tumor growth and (B) percentage change of body weight curves of nude mice bearing HT-1376 cell xenograft after intravenous injection with saline, free DOX, DOX-loaded MSNs@PDA and DOX-loaded MSNs@PDA-PEP (n =5). *p < 0.05; **p < 0.01.
Figure 9.
Figure 9.
H&E analyses of tumors and major organs of nude mice bearing HT-1376 cell xenograft after treatments with saline, free DOX, DOX-loaded MSNs@PDA and DOX-loaded MSNs@PDA-PEP.
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