A Nanostopper Approach To Selectively Engineer the Surfaces of Mesoporous Silicon

Successful applications of mesoporous materials often require different surface properties of internal pore walls and external surfaces. The different functional moieties on the different surfaces enable them to fulfill multiple application demands. In this study, we introduce a nanostopper approach to selectively functionalize the different surfaces of porous silicon (PSi). The external surface was functionalized with amine groups to further graft with folic acid (FA) and fluorescein isothiocyanate (FITC) for targeting and imaging, respectively. The pore walls were functionalized with carboxyl groups to obtain a higher loading degree of doxorubicin and realize a pH-triggered drug release. The engineered PSi drug carrier showed specific targeting against cancer cells and improved cell internalization due to the FA functionalization. Moreover, the PSi carrier presented an intracellular drug delivery with pH-triggered functionality. With the selective modification, the loading degree of the drug was increased 4-fold without any compromise in the toxicity of the plain carrier

Smart Porous Silicon Nanoparticles with Polymeric Coatings for Sequential Combination Therapy

In spite of the advances in drug delivery, the preparation of smart nanocomposites capable of precisely controlled release of multiple drugs for sequential combination therapy is still challenging. Here, a novel drug delivery nanocomposite was prepared by coating porous silicon (PSi) nanoparticles with poly­(beta-amino ester) (PAE) and Pluronic F-127, respectively. Two anticancer drugs, doxorubicin (DOX) and paclitaxel (PTX), were separately loaded into the core of PSi and the shell of F127. The nanocomposite displayed enhanced colloidal stability and good cytocompatibility. Moreover, a spatiotemporal drug release was achieved for sequential combination therapy by precisely controlling the release kinetics of the two tested drugs. The release of PTX and DOX occurred in a time-staggered manner; PTX was released much faster and earlier than DOX at pH 7.0. The grafted PAE on the external surface of PSi acted as a pH-responsive nanovalve for the site-specific release of DOX. <i>In vitro</i> cytotoxicity tests demonstrated that the DOX and PTX coloaded nanoparticles exhibited a better synergistic effect than the free drugs in inducing cellular apoptosis. Therefore, the present study demonstrates a promising strategy to enhance the efficiency of combination cancer therapies by precisely controlling the release kinetics of different drugs

Amine Surface Modifications and Fluorescent Labeling of Thermally Stabilized Mesoporous Silicon Nanoparticles

Mesoporous silicon (PSi) has been shown to have extensive application opportunities in biomedicine, whereas it has frequently failed to produce complex systems based on PSi due to the lack of surface functional groups or the instability of the unmodified PSi surface. In the present study, PSi nanoparticles, stabilized by thermal oxidation or thermal carbonization, were successfully modified by grafting aminosilanes on the surface. The modifications were performed by covalently bonding 3-triethoxysilylpropylamine (APTES) or 3-(2-aminoethylamino) propyldimethoxymethylsilane (AEAPMS) on thermally oxidized PSi (TOPSi) and thermally carbonized PSi (TCPSi). These materials were systematically characterized with N₂ ad/desorption, TEM, contact angle, zeta potential, FT-IR, ²⁹Si CP/MAS NMR, and elemental analysis. To evaluate their application potentials, a fluorescent dye, fluorescein 5-isothiocyanate (FITC), was coupled on the surface of amine-modified nanoparticles. The effects of PSi matrix and surface amino groups on FITC coupling efficiency, fluorescent intensity, and the stability of fluorescence in simulated body fluid (SBF) were investigated. The nanoparticles modified with AEAPMS had higher FITC coupling efficiency than those modified with APTES. FITC-coupled TOPSi nanoparticles also possessed brighter fluorescence and better fluorescent stability in SBF. Furthermore, due to the protection caused by the mesoporous structure of PSi nanoparticles, the FITC-coupled TOPSi nanoparticles showed superior photostability in photobleaching experiment

Scalable Synthesis of Biodegradable Black Mesoporous Silicon Nanoparticles for Highly Efficient Photothermal Therapy

Porous silicon (PSi) has attracted wide interest as a potential material for various fields of nanomedicine. However, until now, the application of PSi in photothermal therapy has not been successful due to its low photothermal conversion efficiency. In the present study, biodegradable black PSi (BPSi) nanoparticles were designed and prepared via a high-yield and simple reaction. The PSi nanoparticles possessed a low band gap of 1.34 eV, a high extinction coefficient of 13.2 L/g/cm at 808 nm, a high photothermal conversion efficiency of 33.6%, good photostability, and a large surface area. The nanoparticles had not only excellent photothermal properties surpassing most of the present inorganic photothermal conversion agents (PCAs) but they also displayed good biodegradability, a common problem encountered with the inorganic PCAs. The functionality of the BPSi nanoparticles in photothermal therapy was verified in tumor-bearing mice in vivo. These results showed clearly that the photothermal treatment was highly efficient to inhibit tumor growth. The designed PCA material of BPSi is robust, easy to prepare, biocompatible, and therapeutically extremely efficient and it can be integrated with several other functionalities on the basis of simple silicon chemistry

Tailored Dual PEGylation of Inorganic Porous Nanocarriers for Extremely Long Blood Circulation in Vivo

Drug carrier systems based on mesoporous inorganic nanoparticles generally face the problem of fast clearance from bloodstream thus failing in passive and active targeting to cancer tissue. To address this problem, a specific dual PEGylation (DPEG) method for mesoporous silicon (PSi) was developed and studied in vitro and in vivo. The DPEG coating changed significantly the behavior of the nanoparticles in vivo, increasing the circulation half-life from 1 to 241 min. Furthermore, accumulation of the coated particles was mainly taking place in the spleen whereas uncoated nanoparticles were rapidly deposited in the liver. The protein coronas of the particles differed considerably from each other. The uncoated particles had substantially more proteins adsorbed including liver and immune active proteins, whereas the coated particles had proteins capable of suppressing cellular uptake. These reasons along with agglomeration observed in blood circulation were concluded to cause the differences in the behavior in vivo. The biofate of the particles was monitored with magnetic resonance imaging by incorporating superparamagnetic iron oxide nanocrystals inside the pores of the particles making dynamic imaging of the particles feasible. The results of the present study pave the way for further development of the porous inorganic delivery system in the sense of active targeting as the carriers can be easily chemically modified allowing also magnetically targeted delivery and diagnostics

Tailored Dual PEGylation of Inorganic Porous Nanocarriers for Extremely Long Blood Circulation in Vivo

Drug carrier systems based on mesoporous inorganic nanoparticles generally face the problem of fast clearance from bloodstream thus failing in passive and active targeting to cancer tissue. To address this problem, a specific dual PEGylation (DPEG) method for mesoporous silicon (PSi) was developed and studied in vitro and in vivo. The DPEG coating changed significantly the behavior of the nanoparticles in vivo, increasing the circulation half-life from 1 to 241 min. Furthermore, accumulation of the coated particles was mainly taking place in the spleen whereas uncoated nanoparticles were rapidly deposited in the liver. The protein coronas of the particles differed considerably from each other. The uncoated particles had substantially more proteins adsorbed including liver and immune active proteins, whereas the coated particles had proteins capable of suppressing cellular uptake. These reasons along with agglomeration observed in blood circulation were concluded to cause the differences in the behavior in vivo. The biofate of the particles was monitored with magnetic resonance imaging by incorporating superparamagnetic iron oxide nanocrystals inside the pores of the particles making dynamic imaging of the particles feasible. The results of the present study pave the way for further development of the porous inorganic delivery system in the sense of active targeting as the carriers can be easily chemically modified allowing also magnetically targeted delivery and diagnostics