Osteosarcoma remains a challenging malignancy due to its aggressive metastasis and resistance to conventional therapies. But the integration of nanotechnology with traditional Chinese medicine offers a transformative approach to overcoming challenges in herbal utilization and cancer therapy. Here, we report the discovery of self-assembled nanoparticles formed during the co-decoction of pyritum and corni fructus, representing a novel mechanism underlying traditional Chinese medicine synergy. Notably, the nanoparticles demonstrate magnetic resonance imaging (MRI) capability with a high T₁ relaxation rate and low r₂/r₁ ratio (1.53), positioning them as promising T₁ contrast agents. Inspired by this natural self-assembly process, we engineer a pH-responsive nanoplatform by conjugating gallic acid, polydopamine, and alendronate onto porous FeS₂ nanoparticles (FGPA). FGPA achieves multi-therapy through drug release, photothermal ablation, H₂S-mediated bioenergetic collapse, and ferroptosis induction. In vivo orthotopic models demonstrate almost tumor regression treated with FGPA and near-infrared irradiation, while maintaining biosafety. Additionally, FGPA serves as a dual-modal photoacoustic (PA) / MRI contrast agent, enabling image-guided therapy with pH-responsive T₁ relaxation enhancement. This work bridges traditional Chinese medicine and nanotechnology, establishing a paradigm for developing multifunctional traditional Chinese medicine-based theranostic agents.

Breast cancer has always been a research hotspot in the medical field due to its highest incidence and mortality rates among women worldwide. However, the significant molecular heterogeneity of breast cancer presents major challenges for its diagnosis and treatment. Surface-enhanced Raman spectroscopy (SERS) has gained considerable attention for its capability in trace detection and molecular analysis. To accurately identify different breast cancer cell subtypes, constructing reliable SERS bioprobes is essential. Therefore, a specific highly expressed receptor, human epidermal growth factor receptor 2 (HER-2), was employed to explore SERS bioprobes in this study. Two bioprobes capable of targeting breast cancer cells, Au NPs@4-MBA@PDA@aHER-2 and Au NPs@4-MPY@PDA@aHER-2, were synthesized. SERS performance testing indicated that the Au NPs were able to detect and trace molecules at concentrations as low as 2 × 10^–9 mol/L. Additionally, the two bioprobes exhibited good spectral stability with a relative standard deviation (RSD) of 9.58%. Moreover, by constructing a “symphonic SERS spectra” of the two bioprobes with prominent component analysis-linear discriminant analysis (PCA-LDA), the classification accuracy of distinguishing white blood cells (WBCs) and two breast cancer cell subtypes (SK-BR-3 and MDA-MB-231) reached up to 97.33%. The integration of machine learning with SERS detection provides a novel technological pathway for the early diagnosis and personalized treatment of breast cancer.

Photothermal therapy (PTT) has received a lot of attention as a promising strategy for eliminating tumors quickly. However, the unavoidable inflammatory response during the treatment might result in a high concentration of M2-like tumor-associated macrophages (TAMs), increasing the risk of tumor recurrence and metastasis. To address this problem, gold-based nanocarriers (PGMP-small interfering RNA (siRNA) nanoparticles (NPs)) containing STAT6siRNA, that inhibited M2-like TAM polarization, were designed and investigated for PTT and gene therapy of non-small cell lung cancer (NSCLC). In an NSCLC model, the nanocarriers demonstrated excellent siRNA delivery ability and a high gene transfection rate of up to 90% in macrophages, thus inhibiting the polarization of about 87% of M2-like TAMs and effectively suppressing the invasion and metastasis of NSCLC. Meanwhile, the unique gold nanosphere structure offered improved PTT and contrast-enhanced ultrasound imaging, thus contributing to the efficient elimination and real-time monitoring of the tumor tissues. These nanocarriers with combined gene and photothermal therapeutic capabilities improved the efficacy of single-modality treatment, and showed the potential to inhibit cancer cell recurrence and metastasis to ultimately cure NSCLC.

The recent advances in nanoscience and nanotechnology have enhanced the synthesis of various forms of nanomaterials for practical applications. Undoubtedly, these nanomaterials are not without attendant toxicities to humans, environment, and other organisms. Moreover, the toxicity of nanomaterials dominates the landscape of current toxicity concerns highlighted by the FDA. Titanium dioxide nanoparticles (TiO₂ NPs) contribute a large proportion of synthesized nanomaterials mainly due to their excellent photocatalytic activities, mechanical and chemical stability, bio- and chemical inertness, corrosion resistance, thin film transparency, and low production cost. These fascinating properties of TiO₂ NPs have been extensively exploited and dramatically increased their utility for various applications such as in nanomedicine for cancer theranostics, nanobiotechnology, environment, pharmacy, energy, food, cosmetics, and paper industries. Owing to the poor understanding of the impacts of NPs on humans, no clear regulation has been implemented for NPs among international authorities. Over time, the toxicity state of TiO₂ NPs is typical of a double-edged sword. Hitherto, there is no restriction on the use of TiO₂ NPs irrespective of the toxicity concerns raised by some researchers. This may have been dampened by the low-to-no toxicity reports from other researchers on these NPs. This review therefore looks into the recent toxicity reports from various studies conducted with/on TiO₂ NPs as to ascertain their present-day safety. To elucidate this, we discussed the possible exposure routes to these NPs and their effects on the environment, plants, soil organisms, and aquatic species. We also provided insights on the toxicity mechanisms of TiO₂ NPs and proposed future perspectives for improving their safe applications.

As nanomedicine-based clinical strategies have continued to develop, the possibility of combining chemotherapy and singlet oxygen-dependent photodynamic therapy (PDT) to treat pancreatic cancer (PaC) has emerged as a viable therapeutic modality. The efficacy of such an approach, however, is likely to be constrained by the mechanisms of drug release and tumor oxygen levels. In the present study, we developed an Fe(III)-complexed porous coordination network (PCN) which we then used to encapsulate PTX (PCN-Fe(III)-PTX) nanoparticles (NPs) in order to treat PaC via a combination of chemotherapy and PDT. The resultant NPs were able to release drug in response to both laser irradiation and pH changes to promote drug accumulation within tumors. Furthermore, through a Fe(III)-based Fenton-like reaction these NPs were able to convert H₂O₂ in the tumor site to O₂, thereby regulating local hypoxic conditions and enhancing the efficacy of PDT approaches. Also these NPs were suitable for use as a T₁-magnetic resonance imaging (MRI) weighted contrast agent, making them viable for monitoring therapeutic efficacy upon treatment. Our results in both cell line and animal models of PaC suggest that these NPs represent an ideal agent for mediating effective MRI-guided chemotherapy-PDT, giving them great promise for the clinical treatment of PaC.

Janus nanoparticles (JNPs) have multiple configurations for molecular imaging, targeting, and therapeutic effects on cancers; these properties have made these particles attractive for biomedical applications. Nonetheless, smart strategies for the controlled synthesis in a liquid phase and exploration of the appropriate applications of JNPs remain a challenge. In this study, a unique liquid-phase method was applied to fabricate Mn₃O₄-TiO₂/ZnO/Fe₃O₄ multifunctional binary transition metal oxide-based JNPs, using the concept of epitaxial growth and lattice mismatch among synthesized materials. Transmission electron microscopy and scanning transmission electron microscopy results revealed that the created materials are embedded in the form of dimers with good dispersion and homogeneous growth in a nonpolar solvent. Pluronic® F-127-coated Mn₃O₄- TiO₂ JNPs were utilized as a contrast agent in T₁-weighted magnetic resonance imaging (MRI) and in photodynamic therapy (PDT) for cancers in vitro and in vivo. In vivo T₁-weighted MRI of the heart, liver, and kidneys in mice after intravenous injection of the nanoparticles revealed high sensitivity and biocompatibility of as-synthesized Mn₃O₄-TiO₂ JNPs. Results of synchrotron X-ray fluorescence microscopy mapping showed the stability of the nanocomposites and efficiency of penetration into the cytoplasm and perinuclear area. Inorganic TiO₂ photosensitizers showed promising tumor ablation performance in PDT in vitro and in vivo at low intensity of UV irradiation (5.6 mW·cm^-2) because of their ultrasmall size and photodegradable stability. These results reveal that multifunctional Mn₃O₄-TiO₂ JNPs enhance a T₁-weighted MRI contrast and have excellent properties for PDT and therefore, may be a novel agent for cancer theranostics.