Background: Recent developments in nanotechnology have provided efficient and promising methods for the treatment of diseases to achieve better therapeutic results and lower side effects. Titanium dioxide (TiO₂) nanomaterials are emerging inorganic nanomaterials with excellent properties such as low toxicity and easy functionalization. TiO₂ with special nanostructures can be used as delivery vehicles for drugs, genes and antigens for various therapeutic options. The exploration of TiO₂-based drug delivery systems shows great promise for translating nanotechnology into clinical applications; Methods: Comprehensive data on titanium dioxide were collected from reputable online databases including PubMed, GreenMedical, Web of Science, Google Scholar, China National Knowledge Infrastructure Database, and National Intellectual Property Administration; Results: In this review, we discuss the synthesis pathways and functionalization strategies of TiO₂. Recent advances of TiO₂ as a drug delivery system, including sustained and controlled drug release delivery systems were introduced. Rigorous long-term systematic toxicity assessment is an extremely critical step in application to the clinic, and toxicity is still a problem that needs to be closely monitored; Conclusions: Despite the great progress made in TiO₂-based smart systems, there is still a great potential for development. Future research may focus on developing dual-reaction delivery systems and single-reaction delivery systems like redox and enzyme reactions. Undertaking thorough in vivo investigations is necessary prior to initiating human clinical trials. The high versatility of these smart drug delivery systems will drive the development of novel nanomedicines for personalized treatment and diagnosis of many diseases with poor prognosis.

Mesoporous titanium nanoparticles (MTN) have always been a concern and are considered to have great potential for overcoming antibiotic-resistant bacteria. In our study, MTN modified with functionalized UV-responsive ethylene imine polymer (PEI) was synthesized. The characterization of all products was performed by different analyses, including SEM, TEM, FT-IR, TGA, XRD, XPS, and N₂ adsorption-desorption isotherms. The typical antibacterial drug berberine hydrochloride (BH) was encapsulated in MTN-PEI. The process exhibited a high drug loading capacity (22.71 ± 1.12%) and encapsulation rate (46.56 ± 0.52%) due to its high specific surface area of 238.43 m²/g. Moreover, UV-controlled drug release was achieved by utilizing the photocatalytic performance of MTN. The antibacterial effect of BH@MTN-PEI was investigated, which showed that it could be controlled to release BH and achieve a corresponding antibacterial effect by UV illumination for different lengths of time, with bacterial lethality reaching 37.76% after only 8 min of irradiation. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the nanoparticles have also been studied. The MIC of BH@MTN-PEI was confirmed as 1 mg/mL against Escherichia coli (E. coli), at which the growth of bacteria was completely inhibited during 24 h and the concentration of 5 mg/mL for BH@MTN-PEI was regarded as MBC against E. coli. Although this proof-of-concept study is far from a real-life application, it provides a possible route to the discovery and application of antimicrobial drugs.

Cardiac glycosides from Periplocae Cortex are bioactive constituents, but isolating and structurally confirming their trace in vivo metabolites remains challenging because authentic standards are often unavailable. We developed a steroid-core fragment-guided strategy based on the diagnostic ion at m/z 355.2270 that integrates metabolite screening, targeted purification, and structural characterization. Periplocin-related analytes were detected in rat urine and plasma after oral periplocin administration using HPLC-QQQ-MS/MS and UPLC-Q-TOF-MS/MS. Guided by the diagnostic ion, 13 L of rat urine was fractionated using macroporous resin, Sephadex LH-20, ODS chromatography, and preparative HPLC. Two trace metabolites were isolated and identified as gomphogenin (M1, 4 mg) and 17α-asclepioside (M2, 8 mg) by HR-MS and NMR spectroscopy. Periplocin, periplogenin, and periplocymarin were confirmed using reference standards. Structural comparison supported a putative transformation pathway involving deglycosylation and steroid-core modification. In a hypoxia/reoxygenation-injured H9c2 cell model, M1 and M2 increased cell viability at 50 μM, supporting further evaluation using complementary cellular endpoints. This diagnostic-ion-guided workflow enables the targeted isolation of trace cardenolide metabolites from biological matrices and provides reference compounds for future pharmacokinetic and pharmacological studies.