MUC1 aptamer-capped mesoporous silica nanoparticles for controlled drug delivery and radio-imaging applications

doi:10.1016/j.nano.2017.08.006

Nanomedicine: Nanotechnology, Biology and Medicine

Volume 13, Issue 8, November 2017, Pages 2495-2505

https://doi.org/10.1016/j.nano.2017.08.006 Get rights and content

Abstract

Mucin 1 (MUC1) is a cell surface protein overexpressed in breast cancer. Mesoporous silica nanoparticles (MSNs) loaded with safranin O, functionalized with aminopropyl groups and gated with the negatively charged MUC1 aptamer have been prepared (S1-apMUC1) for specific targeting and cargo release in tumoral versus non-tumoral cells. Confocal microscopy studies showed that the S1-apMUC1 nanoparticles were internalized in MDA-MB-231 breast cancer cells that overexpress MUC1 receptor with subsequent pore opening and cargo release. Interestingly, the MCF-10-A non-tumorigenic breast epithelial cell line that do not overexpress MUC1, showed reduced (S1-apMUC1) internalization. Negligible internalization was also found for S1-ap nanoparticles that contained a scrambled DNA sequence as gatekeeper. S2-apMUC1 nanoparticles (similar to S1-apMUC1 but loaded with doxorubicin) internalized in MDA-MB-231 cells and induced a remarkable reduction in cell viability. Moreover, S1-apMUC1 nanoparticles radio-labeled with ^99mTc (S1-apMUC1-Tc) showed a remarkable tumor targeting in in vivo studies with MDA-MB-231 tumor-bearing Balb/c mice.

Graphical Abstract

Mesoporous silica nanoparticles loaded with a dye, capped with MUC1 aptamer and radiolabeled with ^99mTc are used for tumor imaging in mice.

Section snippets

Methods

Syntheses of the nanoparticles are detailed in the Supporting Information.

Design and synthesis of aptamer-capped nanoparticles

MSNs were prepared following known procedures.⁵² The pores of the final calcined MSNs were loaded with safranin O and the external surface of the nanoparticles functionalized with (3-aminopropyl) triethoxysilane (solid S1). Aminopropyl moieties were positively charged at a neutral pH and they are known to display electrostatic and hydrogen bonding interactions with negatively charged aptamers. Therefore, the addition of MUC1 aptamer to a suspension of S1 nanoparticles resulted in pore capping,

Discussion

PXRD and TEM of S1 evidenced that the process of loading the pores with safranin O and the functionalization of the external surface with aminopropyl groups did not modify the mesoporous structure. Moreover, adsorption–desorption isotherms of calcined MSNs showed a typical curve for mesoporous silica (see Supporting Information), which consisted in an adsorption step at intermediate P/P₀ value (0.1–0.3). Narrow BJH pore distribution and absence of a hysteresis loop within this interval

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: Acknowledgment: Ll. P. is grateful to the Universitat Politècnica de València for his grant. A.G-F. is grateful to the Spanish government for her FPU grant.

: Authors Contributions: LlP prepared and characterized the nanoparticles and collaborated in the imaging and bio‐distribution studies. AG‐F carried out the cell viability, cell uptake and anti‐tumoral studies. BdL. collaborated in the preparation and characterization of the nanoparticles. CC‐C, ESB, MSA and RS‐O carried out the radiolabeling, imaging and bio‐distribution studies. SM prepared and characterized the MUC‐1 aptamer. SM, MO, RMM, RS‐O and FS planned the assays and also written and revised the manuscript.

: Financial support information: Financial support from the Spanish Government and FEDER funds (Project MAT2015-64139-C4-1) and the Generalitat Valenciana (Project PROMETEOII/2014/047) is gratefully acknowledged.

¹: These authors contributed equally to this work.

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Original ArticleMUC1 aptamer-capped mesoporous silica nanoparticles for controlled drug delivery and radio-imaging applications

Abstract

Graphical Abstract

Section snippets

Methods

Design and synthesis of aptamer-capped nanoparticles

Discussion

J Control Release

Nucl Med Biol

Bioconjug Chem

Eur J Cancer Suppl

Biosens Bioelectron

Nanotechnology: Basic Science and Emerging Technologies

Recent advances in nanomedicine: applications in diagnostic and therapeutics

Adv Nanomater

Nanomedicine and its applications

J Chem Pharm Res

Nanotechnology and Drug Delivery

Drug delivery vehicles with improved encapsulation Effciency: taking advantage of specific drug-carrier interactions

Expert Opin Drug Deliv

Mesoporous silica nanoparticles for drug delivery and biosensing applications

Adv Funct Mater

The Supramolecular Chemistry of Organic-Inorganic Hybrid Materials

Gated materials for on-command release of guest molecules

Chem Rev

Gated silica mesoporous supports for controlled release and signaling applications

Acc Chem Res

Gated silica mesoporous materials in sensing applications

ChemOpen

Towards biocompatible Nanovalves based on mesoporous silica nanoparticles

Med Chem Commun

Design of Enzyme-Mediated Controlled Release Systems Based on silica mesoporous supports capped with Ester-glycol groups

Langmuir

Targeted cargo delivery in senescent cells using capped mesoporous silica nanoparticles

Angew Chem Int Ed

Cytosine-phosphodiester-guanine Oligodeoxynucleotide (CpG ODN)-capped hollow mesoporous silica particles for enzyme-triggered drug delivery

Dalton Trans

Enzyme-mediated controlled release systems by anchoring peptide sequences on mesoporous silica supports

Angew Chem Int Ed

Enzyme-responsive silica mesoporous supports capped with Azopyridinium salts for controlled delivery applications

Chem A Eur J

Enzyme-responsive snap-top covered silica Nanocontainers

J Am Chem Soc

Bitoin-Avidin as a protease responsive cap system for controlled guest release from colloidal mesoporous silica

Angew Chem Int Ed

Highly specific dual enzyme-mediated payload release from peptide-coated silica particles

J Am Chem Soc

DNA switches: from principles to applications

Angew Chem Int Ed

DNA nanotechnology: from sensing and DNA machines to drug-delivery systems

ACS Nano

An aptamer-gated silica mesoporous material for thrombin detection

Chem Commun

Aptamer-capped multifunctional mesoporous strontium hydroxyapatite Nanovehicle for cancer-cell-responsive drug delivery and imaging

Biomacromolecules

Original Article
MUC1 aptamer-capped mesoporous silica nanoparticles for controlled drug delivery and radio-imaging applications