Multifunctional Mesoporous Silica Nanoparticles for Cancer‐Targeted and Controlled Drug Delivery

Abstract

Multifunctional mesoporous silica nanoparticles are developed in order to deliver anticancer drugs to specifi c cancer cells in a targeted and controlled manner. The nanoparticle surface is functionalized with amino-β -cyclodextrin rings bridged by cleavable disulfi de bonds, blocking drugs inside the mesopores of the nanoparticles. Poly(ethylene glycol) polymers, functionalized with an adamantane unit at one end and a folate unit at the other end, are immobilized onto the nanoparticle surface through strong β -cyclodextrin/adamantane complexation. The non-cytotoxic nanoparticles containing the folate targeting units are effi ciently trapped by folate-receptor-rich HeLa cancer cells through receptor-mediated endocytosis, while folate-receptor-poor human embryonic kidney 293 normal cells show much lower endocytosis towards nanoparticles under the same conditions. The nanoparticles endocytosed by the cancer cells can release loaded doxorubicin into the cells triggered by acidic endosomal pH. After the nanoparticles escape from the endosome and enter into the cytoplasm of cancer cells, the high concentration of glutathione in the cytoplasm can lead to the removal of the β -cyclodextrin capping rings by cleaving the pre-installed disulfi de bonds, further promoting the release of doxorubicin from the drug carriers. The high drug-delivery effi cacy of the multi functional nanoparticles is attributed to the co-operative effects of folatemediated targeting and stimuli-triggered drug release. The present delivery system capable of delivering drugs in a targeted and controlled manner provides a novel platform for the next generation of therapeutics.

Advanced drug delivery nanosystems (aDDnSs): a mini-review

“…Various delivery systems including liposomes, dendrimers and polymersomes and particulate drug carriers have been designed and developed so far. The delivery of active substances or candidate drugs can be improved by advanced DDS such as previously described, using therapeutic colloidal nanocarriers and/or inorganic materials (Yang et al, 2012;Zhang et al, 2012;Liu et al, 2013), including polymeric nanoparticles, micelles (Torchilin, 2007), polymeric micelles (Torchilin, 2004), nanotubes (Li et al, 2010) and nanorobits (Kostarelos, 2010;Igbal et al, 2012).…”

“…In the recent literature, mixed nanosystems combing biomaterials and inorganic materials have been introduced for biomedical applications (Yang et al, 2012;Zhang et al, 2012;Liu et al, 2013). The external and/or the internal part of the system could be established by using advanced analytical, chromatographic and spectroscopic techniques.…”

Mesoporous calcium–silicon xerogels with mesopore size and pore volume influence hMSC behaviors by load and sustained release of rhBMP-2

“…6,7 Recently, the application of mesoporous materials for bone regeneration has been proposed, and the tunable pore size and high pore volume of the mesoporous materials might allow them to load osteogenic agents and promote new bone tissue regeneration. 6,8 The biomacromolecule bone morphogenetic protein (BMP) with strong boneinducing activity has been considered to play important roles in bone regeneration. [9][10][11] Furthermore, recombinant human bone morphogenetic protein-2 (rhBMP-2) has Dovepress Dovepress 1716 song et al received US Food and Drug Administration approval for application in the enhancement of lumbar spine fusion and treatment of acute tibial fractures.…”

Study on the use of 3‐aminopropyltriethoxysilane and 3‐chloropropyltriethoxysilane to surface biochemical modification of a novel low elastic modulus Ti–Nb–Hf alloy

“…This problem can be overcome, at least in part, by adding a preliminary activation treatment. For pure titanium, there is a large diversity of examples in the literature suggesting different activation methods to provide reactive groups for covalent immobilization of biomolecules (mainly -OH groups) [2][3][4][5][6][7][8][9][10][11] and organosilanes bearing different functional groups [12][13][14][15][16][17]. Recently, a comparative study between two activation methods frequently used (Oxygen plasma and Piranha solution) was performed by V. Paredes [18].…”

“…Nowadays, organosilane precursors bearing functional groups such as amino [12][13][14][15][16][17][18][19][20][21][22], thiol, carboxyl, phosphate, vinyl [23][24][25], cyanide [26], phenyl [24,27] or sulphhydryl groups are readily available. Despite the wide variety of silane precursors available for surface modification, the majority of studies have employed aminosilanes, in particular 3-aminopropyltriethoxysilane (APTES) [11][12][13][14][15][16][17][18][19][20][21][22]. Nevertheless, the 3-chloropropyltriethoxysilane (CPTES) is also proposed by other authors [2,4,10].…”