Project Significance

The starting point of our project is to address the protein modification dilemma of nano-silicon dioxide and create a modular modification platform that endows nano-silicon dioxide with enhanced biological functionality. Therefore, we need to understand the current status of protein modification of nano-silicon dioxide to assess the significance of our project.

One of the most valuable practical applications of our project is the use of nano-silica dioxide as a drug carrier [1]. To further validate the broader practical applicability of our project, we consulted Professor Meng and asked many related questions. He informed us that currently, nano-silica dioxide intravenous injections have received approval from the U.S. FDA, while the micrometer-level oral drug GRACE has obtained approval from the European Union. Therefore, nano-silica dioxide as a drug carrier holds boundless potential for the future. We also believe that this modular platform will have even broader applications in the future.

Professor Meng Huan, a researcher at the National Nanotechnology Center and an expert in the fields of nanopharmacy, drug delivery, and nano-bio interfaces, explained that unmodified nano-silicon dioxide has poor colloidal stability, making it prone to aggregation and resulting in its structural instability in the body's environment. Protein modification is an effective strategy to enhance colloidal stability, making it imperative to modify nano-silicon dioxide with proteins to fully unleash its potential.

Professor Meng also pointed out that protein modification of nano-silicon dioxide currently faces numerous challenges, especially in terms of high cost and complex processes. When exploring modification methods, higher-cost proteins require a larger budget. Our modular modification platform design, however, simplifies the process and reduces costs, carrying significant implications.

[1]Huang, R., Shen, Y. W., Guan, Y. Y., Jiang, Y. X., Wu, Y., Rahman, K., Zhang, L. J., Liu, H. J., & Luan, X. (2020). Mesoporous silica nanoparticles: facile surface functionalization and versatile biomedical applications in oncology. Acta biomaterialia, 116, 1–15. https://doi.org/10.1016/j.actbio.2020.09.009

Safety

In the process of promoting our project, we often encounter skepticism regarding the safety of nano-silicon dioxide as a drug carrier. There is a widespread concern among people that nano-silicon dioxide may trigger "silicosis," prompting us to urgently investigate the safety of nano-silicon dioxide as a drug carrier. We also expressed our concerns to Professor Meng Huan, who has a deep understanding of nanosafety.

Professor Meng's response put our minds at ease. He told us that having doubts about the safety of nano-silicon dioxide as a drug carrier is incorrect. In fact, the safety of nano-silicon dioxide depends on its production process, as different processes can affect the type and density of silicon hydroxyl groups. Nano-silicon dioxide produced at high temperatures often forms highly strained three-membered rings, making it highly unstable and prone to ring-opening reactions and the generation of free radicals, which can lead to safety concerns. On the contrary, nano-silicon dioxide produced at low temperatures typically forms less strained four-membered rings, resulting in a higher safety profile.

Therefore, the safety of nano-silicon dioxide as a drug carrier can be considered quite reassuring.

How to improve our project design

Stage 1:

Design:

The pollution caused by worn-out car tires is enormous, and its harm is even greater than exhaust emissions. Therefore, green tires have become a new trend in the tire industry. Currently, nano SiO2 is used to produce green tires. However, there are a large number of hydroxyl groups on the surface of silicon dioxide, which gives it a strong affinity for water. As a result, the silicon dioxide surface is covered by adsorbed water, making it difficult to blend with rubber. The current solution to this problem involves chemical methods, but these methods are not only harsh but also environmentally unfriendly. We hope to utilize synthetic biology methods by using hydrophobic peptides to modify silicon dioxide, making it easier to incorporate into rubber for the production of green tires.

Recommendation:

Since the value of nano-scale silicon dioxide is not limited to this application alone, such as serving as a delivery carrier and enzyme scaffold, we suggest exploring more potential uses for silicon dioxide. At the same time, the PIs propose a new idea that suggests we can create a silicon dioxide modification platform, allowing silicon dioxide to be easily and artificially modified.

Stage 2:

Design:

Based on the PI's suggestion, we have discovered that nano-scale silicon dioxide, when modified with proteins, can have a broader range of applications. However, existing modification methods are complex and costly. Therefore, we hope to construct a modification platform that can modularly modify nano-scale silicon dioxide, expanding its practical applications.

To achieve protein modification of nano-scale silicon dioxide, we have identified a protein, LPG, capable of connecting antibodies with silicon dioxide and have modified it. When the linker length is insufficient, the binding capacity of silicon-binding peptide SBP is low. Therefore, we aim to utilize machine learning to enable our engineered bacteria to select the most suitable linker length, thus making it more widely applicable to different proteins.

Recommendation:

When we presented this idea to Professor Wang, a molecular biology expert, he pointed out that linker length is not a core issue. As long as the linker reaches a certain length, it can reduce the steric hindrance effect.

Stage 3:

Due to Professor Wang Zhanxin's suggestion not to limit ourselves to basic design, and to design slinkers based on the actual functions of protein-modified silicon dioxide, we conducted further research on the functionalization of protein-modified mesoporous silicon dioxide. We continued brainstorming and ultimately designed our slinker universe.

Design:

First, we have the core and foundation of our slinker universe - the basic slinker. By modifying LPG and replacing PG with a nucleophile that allows for more extensive linking, we can connect the target protein with biotin to achieve protein modification of silicon dioxide.

Next, we aim to develop Silinkers with the ability to perceive changes in the concentration of certain substances. In drug delivery, concentration changes at different locations need to be sensed for stepwise release. To achieve this, we designed the Twisting slinker. Therefore, our designed Silinker can have the ability to bind specific ions. When binding ions, its structure changes, and the Twisted Silinker curls, bringing the target protein closer to the silicon dioxide.

In the medical application of mesoporous silicon dioxide, protein modification can also play a role in controlling the release of drugs from the mesopores. We designed to cleave the proteins on the pore surface, allowing them to leave the surface of silicon dioxide and expose the pores for drug release. Thus, we envision a Cuttable Silinker that can connect different functional proteins and also act to cleave and release proteins in different environments. We attempt to achieve the replacement of different enzyme cleavage sites by adding "internal peptides" to the ends of the sequences.

By connecting two peptide segments that can recognize different ion concentrations to two Basic Slinkers, we call it the Pairing Slinker. When changes in ion concentration are sensed by the two peptide segments, they are attracted to each other, pulling the two slinkers together. This allows the two target proteins connected by the slinker to come closer and achieve more functions.