Precipitated silica has demonstrated good biosafety, excellent cytocompatibility, and controllable biodegradability in biocompatibility studies, making it a research hotspot in the fields of medicine, biomedical engineering, and green materials. However, its long-term biological effects in nanoparticle form still require in-depth evaluation.

I. Basic Biocompatibility Characteristics of Precipitated Silica
Biosafety Characteristics
As an amorphous nanoscale silica powder, precipitated silica is non-toxic, harmless, and possesses good biocompatibility. It has been approved by the U.S. Food and Drug Administration (FDA) for use in oral and topical medications, cosmetics, and food contact materials. Unlike crystalline silica, precipitated silica does not have a fibrous structure, and long-term inhalation tests have not shown any cases of silicosis. Its irritation index is only 0.44 (on a 0-8 scale), falling within the range of no irritation to mild irritation.

Cytocompatibility Performance
Studies have shown that precipitated silica has good compatibility with various cell types (including macrophages and lung fibroblasts). At low concentrations, precipitated silica does not significantly reduce cell viability or induce significant apoptosis. Characterization using techniques such as laser particle size analysis, infrared spectroscopy (FTIR), and transmission electron microscopy (TEM) shows that the particle size distribution and surface chemical structure of precipitated silica directly affect its interaction with cells.

Influence of Surface Modification on Compatibility
The surface hydroxyl groups of precipitated silica can be chemically modified to regulate its biocompatibility. For example, hydrophobic precipitated silica can be prepared by modification with the silane coupling agent KH-570, achieving an activation index of 94.1% and a DBP absorption of 2.73 mL, significantly improving its compatibility with biomaterials. In addition, modifying precipitated silica with natural deep eutectic solvents (NADES) constructed from bio-based choline chloride (ChCl) and polyols can further enhance its dispersibility and interfacial binding force in biological environments.

II. Applications and Biocompatibility Studies in the Pharmaceutical Field
Drug Carrier Applications
Due to its extremely high specific surface area (200-300 m²/g) and porous structure, precipitated silica is an ideal drug carrier material. It can form physical or chemical bonds with drug molecules, slowing down drug release, and improving drug stability and bioavailability. Studies have shown that silica-based sustained-release agents can achieve slow drug release, increase therapeutic effects, and reduce drug dosage and frequency.
Antibacterial and Anti-inflammatory Effects
Silica has good antibacterial and anti-inflammatory properties and can be used to treat infections and inflammation-related diseases. Its high specific surface area and porous structure enable it to effectively adsorb toxins produced by bacteria and control the development of wound infections. In wound treatment, silica reduces inflammatory response and pain by adsorbing and neutralizing inflammatory mediators.
Applications in Cancer Treatment
In the field of cancer treatment, silica, as a drug carrier, can deliver anti-tumor drugs to tumor sites, enhancing therapeutic effects. Its high specific surface area and porous structure make it an ideal drug carrier, capable of inhibiting tumor growth through photothermal effects and chemical reactions.
Detoxification Function
The strong adsorption properties of silica make it play an important role in the preparation and processing of detoxification drugs. It can effectively remove toxins and harmful substances, reduce the absorption and damage of toxins, and can neutralize toxic components through chemical reactions with toxins.

III. Challenges and Risks of Biocompatibility Studies
Potential Risks of Nanoparticles
Although silica generally exhibits good biocompatibility, its nanoparticle form may pose potential risks. Studies have shown that ultrafine particles (UFPs) have small particle sizes and can be deposited in the lungs, or penetrate alveolar cells and be transported to systemic organs through the blood, binding to target proteins, which may induce or exacerbate diseases. Studies on lead-loaded ultrafine carbon black (Pb-UFCB) show that this type of substance can reduce cell viability, induce early apoptosis, and lead to oxidative stress.
Effects on Cell Function
Studies have found that exposure to 1,4-naphthoquinone-adsorbed carbon black (1,4 NQ-BC) can lead to programmed necrosis of macrophages, prevent the formation of macrophage extracellular traps (METs), and weaken innate immune function. When the black carbon concentration exceeds 40 μg/cm², the survival rate of RAW264.7 cells is below 70%, and their phagocytic capacity is significantly reduced.  Simultaneously, the expression levels of cytokines such as IL-33 and IL-6 are elevated.
Uncertainty regarding long-term biological effects:
Currently, most studies on the biocompatibility of carbon black focus on short-term effects, and there is insufficient data on long-term biological effects. Studies on carbon-based nanomaterials show that these materials may accumulate in the liver and lungs, and even cross the blood-brain barrier, causing oxidative stress reactions. Although carbon black, as an amorphous structure, is safer than crystalline silica, its long-term accumulation effects still require further research.