Nanomaterials promise to improve disease diagnosis and treatment by enhancing the delivery of drugs, genes, biomolecules and imaging agents to specific subcellular targets. In order to optimize nanomaterial design for this purpose, a comprehensive understanding of how these materials are taken up and transported within the cell is required. In this review, we discuss the endocytic pathways employed by different types of nanoparticles with emphasis on the influence of nanoparticle surface modification. The use of pharmacological inhibition to probe internalization and intracellular trafficking pathways of nanoparticles is critically evaluated. Finally, approaches to target-specific delivery of therapeutics via nanoparticles into the cytoplasm and nucleus are addressed.

Titanium dioxide (TiO₂) nanostructures exhibit a broad range of theranostic properties that make them attractive for biomedical applications. TiO₂ nanostructures promise to improve current theranostic strategies by leveraging the enhanced quantum confinement, thermal conversion, specific surface area, and surface activity. This review highlights certain important aspects of fabrication strategies, which are employed to generate multifunctional TiO₂ nanostructures, while outlining post-fabrication techniques with an emphasis on their suitability for nanomedicine. The biodistribution, toxicity, biocompatibility, cellular adhesion, and endocytosis of these nanostructures, when exposed to biological microenvironments, are examined in regard to their geometry, size, and surface chemistry. The final section focuses on recent biomedical applications of TiO₂ nanostructures, specifically evaluating therapeutic delivery, photodynamic and sonodynamic therapy, bioimaging, biosensing, tissue regeneration, as well as chronic wound healing.

In this study, the antibacterial efficacy of NO-releasing porous silicon nanoparticles (pSiNPs) is reported. NO-releasing pSiNPs were produced via the conjugation of S-nitrosothiol (SNO) and S-nitrosoglutathione (GSNO) donors to the nanoparticle surfaces. The release of the conjugated NO caused by the decomposition of the conjugated SNO and GSNO was boosted in the presence of ascorbic acid. The released NO was bactericidal to Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli), and eliminated bacterial growth within 2 h of incubation without compromising the viability of mammalian cells. These results demonstrate the advantages of NO-releasing pSiNPs for antibacterial applications, for example, in chronic wound treatment.

In this study, thermally hydrocarbonised porous silicon nanoparticles (THCpSiNPs) capped with polyethylenimine (PEI) were fabricated, and their potential for small interfering RNA (siRNA) delivery was investigated in an in vitro glioblastoma model. PEI coating following siRNA loading enhanced the sustained release of siRNA, and suppressed burst release effects. The positively-charged surface improved the internalisation of the nanoparticles across the cell membrane. THCpSiNP-mediated siRNA delivery reduced mRNA expression of the MRP1 gene, linked to the resistence of glioblastoma to chemotherapy, by 63% and reduced MRP1-protein levels by 70%. MRP1 siRNA loaded nanoparticles did not induce cytotoxicity in glioblastoma cells, but markedly reduced cell proliferation. In summary, the results demonstrated that non-cytotoxic cationic THCpSiNPs are promising vehicles for therapeutic siRNA delivery.