Functionalization of Alkyne-Terminated Thermally Hydrocarbonized Porous Silicon Nanoparticles With Targeting Peptides and Antifouling Polymers: Effect on the Human Plasma Protein Adsorption

Abstract

Porous silicon (PSi) nanomaterials combine a high drug loading capacity and tunable surface chemistry with various surface modifications to meet the requirements for biomedical applications. In this work, alkyne-terminated thermally hydrocarbonized porous silicon (THCPSi) nanoparticles were fabricated and postmodified using five bioactive molecules (targeting peptides and antifouling polymers) via a single-step click chemistry to modulate the bioactivity of the THCPSi nanoparticles, such as enhancing the cellular uptake and reducing the plasma protein association. The size of the nanoparticles after modification was increased from 176 to 180-220 nm. Dextran 40 kDa modified THCPSi nanoparticles showed the highest stability in aqueous buffer. Both peptide- and polymer-functionalized THCPSi nanoparticles showed an extensive cellular uptake which was dependent on the functionalized moieties presented on the surface of the nanoparticles. The plasma protein adsorption study showed that the surface modification with different peptides or polymers induced different protein association profiles. Dextran 40 kDa functionalized THCPSi nanoparticles presented the least protein association. Overall, these results demonstrate that the "click" conjugation of the biomolecules onto the alkyne-terminated THCPSi nanoparticles is a versatile and simple approach to modulate the surface chemistry, which has high potential for biomedical applications.

Tailoring Porous Silicon for Biomedical Applications: From Drug Delivery to Cancer Immunotherapy

“…In comparison, the 2 kDa PEG–TOPSi nanoparticles dispersion was stable for up to 3 d; dextranylation of THCPSi can also reduce the plasma protein adsorption. Wang et al investigated plasma proteins' association onto the PSi modified with dextran with two different molecular weight (6 and 40 kDa), and the amount of bonded protein was determined by analyzing the opsonized proteins with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE) gel electrophoresis and further verified by mass spectrometry. THCPSi‐Dex40k showed more negligible protein adsorption than the other modification moieties or the unmodified nanoparticles.…”

“…The adsorption of hydrophobin on the surface of THCPSi particles resulted in a change in the protein corona, with the adsorption of both complement C3 fraction and apolipoproteins . On the contrary, after modification of the particles with dextran chains, there was a reduction in the adsorption of proteins with molecular weight higher than 70 kDa, in a fashion dependent on the molecular weight of the dextran . Thus, it has the potent to interact with different intracellular organell and different intracellular proteins.…”

Multimodality Imaging of Silica and Silicon Materials In Vivo

“…The principal surface‐modification methods for PSi include thermal oxidation, thermal carbonization, and hydrocarbonization, the latter two of which render the material extremely resistant to a variety of harsh chemical conditions and “aging” by atmospheric oxygen . Lately, amine‐modification with 3‐aminopropyltriethoxysilane and undecylenic acid for EDC/NHS coupling chemistry and alkyne‐modification for Cu‐catalyzed click chemistry has gained popularity for the conjugation of biomolecules, labels, and polymers to PSi. In pH above 7, PSi degrades to nontoxic orthosilicic acid, which is excreted to urine.…”

Click Coupling Reactions on Flat and Nanostructured Hydrogen‐Passivated Silicon Surfaces

“…H‐terminated silicon surfaces have been turned into alkyne‐terminated “clickable” surfaces via hydrosilylation of terminal dialkynes, where one head group is grafted to the surface leaving a free terminal alkyne that may subsequently be coupled to an azide. The grafting of a n‐diyne followed by a copper catalyzed cycloaddition was first reported in 2008 by Ciampi et al Since then it is a frequently applied strategy to functionalize oxide free silicon electrodes and has been employed to immobilize redox active groups, to functionalize nano particles, solar energy devices, for monolayer induced doping, and patterning self‐assembled monolayer . The modified surfaces have shown remarkable stability and resistance to oxidation .…”