Abstract
This paper proposes a novel type of multifunctional envelope-type mesoporous silica nanoparticle (MSN) to achieve cancer cell targeting and drug-controlled release. In this system, MSNs were first modified by active targeting moiety hyaluronic acid (HA) for breast cancer cell targeting and hyaluronidases (Hyal)-induced intracellular drug release. Then gelatin, a proteinaceous biopolymer, was grafted onto the MSNs to form a capping layer via glutaraldehyde-mediated cross-linking. To shield against unspecific uptake of cells and prolong circulation time, the nanoparticles were further decorated with poly(ethylene glycol) polymers (PEG) to obtain MSN@HA-gelatin-PEG (MHGP). Doxorubicin (DOX), as a model drug, was loaded into PEMSN to assess the breast cancer cell targeting and drug release behaviours. In vitro study revealed that PEG chains protect the targeting ligand and shield against normal cells. After reaching the breast cancer cells, MMP-2 overpressed by cells hydrolyses gelatin layer to deshield PEG and switch on the function of HA. As a result, DOX-loaded MHGP was selectively trapped by cancer cells through HA receptor-mediated endocytosis and subsequently release DOX due to Hyal-catalysed degradation of HA. This system presents successful bienzyme-responsive targeting drug delivery in an optimal fashion and provides potential applications for targeted cancer therapy.
Highlights
This article has been edited by the Royal Society of Chemistry, including the commissioning, peer review process and editorial aspects up to the point of acceptance
Transmission electron microscopy (TEM) images show that the resulting spherical NH2-mesoporous silica nanoparticle (MSN) and MSN@hyaluronic acid (HA) exhibit a welldefined mesostructure
As illustrated in electronic supplementary material, figure S2, MSN@HA shows that a strong absorption band at approximately 1556 cm−1 in the sample can be assigned to the stretching vibration of N−H bending of HA
Summary
Tetraethylorthosilicate (TEOS, 28%), N-Cetyltrimethylammonium bromide (CTAB) and (3-aminopropyl) triethoxysilane (APTES) were purchased from Alfa-Aesar. Glutaraldehyde, N-hydroxysuccinimide (NHS), N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC) and rsos.royalsocietypublishing.org R. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) were purchased from Sigma- 4 Aldrich. Doxorubicin (DOX) hydrochloride , sodium hyaluronate (HA) (MW = 200 kDa) was purchased from Aladdin. Heochst-33342 was purchased from Invitrogen Life Technologies Corporation. Other reagents were obtained from Xilong Reagent Company. Nanopure water (18.2 MΩ) was used in all experiments. All the chemicals were used as received without further purification
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