Due to their low toxicity levels, gallium-based compounds have emerged as novel materials, in particular for potential biomedical applications. The synthesis of gallium nanoparticles (Ga NPs) through sustainable methods is also gaining significant attention as it eliminates the need for complex preparation methods and hazardous chemicals. In this study, we successfully synthesized two types of nanoparticles: gallium and gallium oxide hydroxide (GaOOH) nanoparticles from liquid gallium. This was followed by forming a metal-phenolic network (MPN) surface coating by utilizing tannic acid and ferric chloride in a simple and effective one-pot probe sonication method. This results in the formation of a core-shell structure with nanoparticles at the core surrounded by a robust metal-phenolic network shell. Scanning electron microscopy, X-ray fluorescence, upright fluorescence, and confocal microscopy were used to evaluate MPN formation. The network was found to enhance the fluorescence intensity as well as prolong the fluorescence quality, which is particularly advantageous for cell-targeting applications. Preliminary biological evaluation studies demonstrated promising biocompatibility, and all synthesized materials showed effective cellular uptake in Huh7 cells, which were distributed throughout the cytoplasm without specific organelle targeting. Furthermore, both types of Ga-MPN networks demonstrated excellent antimicrobial activity against Gram-negative (E. coli) and Gram-positive (MRSA) bacteria, highlighting their potential utility in biomedical fields.

Multifunctional bioactive glass (BG) scaffolds that support bone regeneration, therapeutic-ion delivery, and infection control are highly desirable for bone tissue engineering. In this study, foamed sol–gel-derived Sr-doped BG (Sr-BG), Cu-Sr-, Zn-Sr-, and Cu-Zn-Sr-co-doped BG scaffolds were fabricated to evaluate the effects of therapeutic-ion incorporation on architecture, physicochemical properties, degradation, mineralization, cytocompatibility, osteogenic activity, and antibacterial performance. All scaffolds exhibited interconnected macroporosity (100–300 μm), with porosity increasing from 67% to 73% after multi-ion incorporation. Amorphous silicate networks were confirmed, while compressive strengths (1.88–2.12 MPa) were suitable for cancellous and non-load-bearing applications. Controlled degradation over 6 weeks enabled sustained Si, Ca, Sr, Cu, and/or Zn ion release, with Cu-containing scaffolds showing faster dissolution. All compositions rapidly formed a hydroxycarbonate apatite-like layer in simulated body fluid, confirming preserved bioactivity. Extracts were cytocompatible up to 1 mg/mL and supported MC3T3-E1 adhesion, spreading, and migration. The scaffolds enhanced extracellular matrix mineralization and upregulated RUNX2, ALP, COL1A1, OPN, and OCN, indicating osteogenic differentiation. All scaffolds also showed antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Together, Cu/Zn/Sr-BG demonstrated the most promising multifunctional performance, highlighting its potential for non-load-bearing bone regeneration.

Boesenbergia rotunda (fingerroot) is widely used in traditional medicine, and its bioactive compound panduratin A has demonstrated potent antiviral properties. However, the mechanistic basis underlying its anti-hepatitis B virus (HBV) activity remains to be fully elucidated. HBV-infected human hepatocytes (imHCs) were treated with B. rotunda extract, panduratin A, or pinostrobin. Intracellular HBV DNA, secreted HBsAg and HBeAg, and pregenomic RNA (pgRNA) were quantified in dose- and time-dependent experiments. Luciferase reporter assays were used to assess HBV promoter activity. The roles of HNF1α and HNF4α were evaluated by siRNA-mediated knockdown and ectopic gene expression. Drug interaction studies were performed using the KDM5 inhibitor GS-5801 and the capsid assembly modulator NVR-3778. A 3D liver spheroid model was used to validate antiviral effects on HBV DNA and cccDNA. Gene interaction network analysis was conducted to identify central regulatory pathways. B. rotunda extract, panduratin A, and pinostrobin significantly suppressed intracellular HBV DNA, HBsAg, HBeAg, and pgRNA. Panduratin A exhibited the strongest antiviral activity and inhibited preS1, preS2, and core promoter activities. Panduratin A markedly downregulated HNF1α expression, with only modest effects on HNF4α. Knockdown of HNF1α significantly reduced the antiviral efficacy of panduratin A, whereas ectopic HNF1α expression rescued its inhibitory effects. Co-treatment with GS-5801 produced synergistic activity, and combination with NVR-3778 yielded additive antiviral effects. In 3D liver spheroids, panduratin A reduced intracellular HBV DNA and cccDNA with minimal cytotoxicity. Network analysis further identified HNF1α as a key regulatory node modulated by panduratin A. Panduratin A is a potent anti-HBV compound that acts primarily through HNF1α-dependent suppression of HBV transcription and replication. Its efficacy in combination therapy and in 3D liver models highlights its potential as a promising candidate for future HBV treatment strategies.

Acanthopanax trifoliatus (L.) Voss or phak-paem, a traditional Thai plant in the Araliaceae family, has been reported to promote adaptogenic effects for a long time. The leaves have been used as a tonic to improve general weakness and to treat tuberculosis, lung hemorrhages, bruises, ulcers and contusions. The young leaves and the shoots are also eaten as vegetables. A. trifoliatus leaf extract was prepared, and its physical and chemical properties were qualitatively controlled. Three formulations, tablets, drinks and bubbles, were developed from A. trifoliatus standardized leaf extract. The in vitro antioxidant effects of the A. trifoliatus leaf extracts and formulations were evaluated using a DPPH scavenging assay. The hepatoprotective effects of A. trifoliatus leaf extract and formulations were evaluated in the HepG2 cell line using a hepatoprotective assay, the detection of intracellular reactive oxygen species (ROS) levels and the quantification of apoptotic cells and necrotic cells. The mechanism of action for hepatoprotective effects was determined by detecting antioxidant and apoptosis markers using quantitative real-time polymerase chain reaction (qPCR). Standardized extracts of A. trifoliatus leaves were prepared from quality-controlled raw material. The physical properties of the extract were controlled, including loss on drying, total ash, and acid-insoluble ash. It had specific chromatographic fingerprint with total phenolic and total flavonoid contents of 13.44 ± 0.22 g of chlorogenic acid equivalent in 100 g of extract (g

Mango seed kernel extract (MSKE) and its phytochemical compositions were investigated for their anticancer activities and synergistic effects with doxorubicin (DOX) against hepatocellular carcinoma (HCC) in both 2D and 3D culture models. Molecular docking studies were conducted to elucidate the mechanisms of DOX, MSKE, and major phytochemical components against overexpressed HCC-related proteins. Co-delivery of DOX and MSKE demonstrated significant synergistic anticancer activity in both models. A sequential nanotheranostic platform (SNP), consisting of MSKE encapsulated aminated hollow mesoporous silica nanoparticles capped with graphene quantum dots (GQD-MSKE-NH2HMSNs) and DOX encapsulated HMSNs (DOX-HMSNs), was synthesized for HCC treatment. GQD conjugation allowed real-time cellular tracking and photothermal therapy (PTT). The SNP exhibited particle sizes of 96.12 ± 5.12 nm for GQD-MSKE-NH2HMSNs and 94.99 ± 6.30 nm for DOX-HMSNs, both with positive surface charges. Encapsulation efficiency (%EE) and loading capacity (%LC) of GQD-MSKE-NH2HMSNs were 95.50 ± 0.20% and 46.72 ± 1.14%, respectively, while DOX-HMSNs achieved 96.42 ± 2.48 %EE and 29.0 ± 0.70 %LC. GQD-MSKE-NH2HMSNs provided PTT and disrupted the tumor microenvironment, collagen type 1, thereby enhancing the penetration of GQD-MSKE-NH2HMSNs in 3D-HCC spheroids. In parallel, DOX-HMSNs exhibited a pH-responsive drug release behavior, allowing controlled DOX delivery in the acidic tumor area. Therefore, the SNP demonstrated significantly higher anticancer efficacy than the combination of MSKE and DOX at equivalent concentrations and provided the synergistic effect of the triple combination therapy (herbal adjuvant, PTT and chemotherapy) against HCC.

Monkeypox virus (Mpox) has been recognized for causing distinct skin lesions and is primarily transmitted through skin and sexual contact. To date, the transmissibility and pathogenesis of the Mpox virus in distal human lung has never been completely explored. Here the transmission pathways and Mpox tropism on patient-derived air-liquid epithelium (ALE) model fabricated using isolated primary human alveolar epithelial cells (hAECs) were investigated. hAECs were cultured and exposed to the Mpox virus clade IIb isolated from patient. DNA, proteins, and the tropism were elucidated using polymerase chain reaction (PCR), Western blot and high-content fluorescent imaging. Transmission electron microscopy (TEM) was employed to systematically observe the cellular distribution of viral particles. Viral titers were determined by TCID50 assay. Innate immune response and inflammatory mediators were measured using Milliplex® multiplex and ELISA analysis. Pathology at alveolar barrier integrity was determined using transepithelial electrical resistance (TEER) analysis. The study included mock-infected cells as control. Mpox virus significantly infected 42.82% of total hAEC populations. The prominent observed pathology included a significant reduction in TEER values, loss of tight junction protein, presence of tunneling nanotubes (TNTs) and syncytium morphology. Four stages of Mpox biogenesis were clearly observed without significant activation of IL-6, MIP1alpha, TNF-α, and Galectin-9, although IL-1β were subtly promoted. The developed patient-derived ALE is a versatile model for Mpox virus clade IIb infection reflecting respiratory transmission competence of the Mpox. Postinfection lung pathogenesis demonstrated alveolar barrier damage without significant inflammation, raising concerns about possible immune evasion by the virus.

Background: Sorafenib-resistant (SR) hepatocellular carcinoma (HCC) is a current serious problem in liver cancer treatment. Numerous phytochemicals derived from plants exhibit anticancer activity but have never been tested against drug-resistant cells. Methods: Avocado seed extract (APE) isolated by maceration was analysed for its phytochemical composition and anticancer activity. Novel design charge-switchable pH-responsive nanocarriers of aminated mesoporous silica nanoparticles with conjugated galactose (GMSN) were synthesised for delivering APE and their physicochemical properties were characterized. The drug loading efficiency (%LE) and entrapment efficiency (%EE) were evaluated. Anticancer activity of APE loaded GMSN was measured against HCC (HepG2, Huh-7) and SR-HCC (SR-HepG2). Results: Anticancer activity of APE against non-resistant HepG2 (IC50 50.9 f 0.83 gg mL-1), Huh-7 (IC50 42.41 f 1.88 gg mL-1), and SR-HepG2 (IC50 62.58 f 2.29 gg mL-1) cells was confirmed. The APE loaded GMSN had a diameter of 131.41 f 14.41 nm with 41.08 f 2.09%LE and 44.96 f 2.26%EE. Galactose functionalization (55%) did not perturb the original mesoporous structure. The GMSN imparted positive surface charges, 10.3 f 0.61mV at acidic medium pH 5.5 along with rapid release of APE 45% in 2 h. The GMSN boosted cellular uptake by HepG2 and SR-HepG2 cells, whereas the amine functionalized facilitated their endosomal escape. Their anticancer activity was demonstrated in non-resistant HCC and SR-HCC cells with IC50 values at 30.73 f 3.14 (HepG2), 21.86 f 0.83 (Huh-7), 35.64 f 1.34 (SR-HepG2) gg mL-1, respectively, in comparison to the control and non-encapsulated APE. Conclusion: APE loaded GMSN is highly effective against both non-resistant HCC and SR-HCC and warrants further in vivo investigation.

A topical antimicrobial ointment was developed from the fruit extract of Oroxylum indicum and was evaluated for its antibacterial and wound-healing effects and acute toxicity in animal models. O. indicum fruit and seed extracts exhibited antibacterial activities against clinically isolated bacteria and showed in vitro antioxidant activities. To develop a topical antimicrobial ointment from the fruit extract of O. indicum and evaluate for its antibacterial and wound-healing effects. O. indicum fruit extract ointment was prepared and qualitatively controlled. Acute toxicity of the extract was evaluated in the animal model. Antibacterial effects and healing effects of the ointment to the dog wound were investigated. The results are expressed as mean ± standard deviation. The ointment exhibited in vitro antibacterial effects. A single daily application of the ointment to a dog’s wound exhibited a wound-healing effect with complete epithelialization within 7 days while the wound was completely healed with the removal of the scabs, the size was decreased to 14% of the original size within 12 days. The ointment was found no acute toxicity in the animal model. O. indicum ointment promoted in vitro antibacterial activity and wound-healing effect in dogs with no acute toxicity.

Liver spheroids may be the best alternative models for evaluating efficacy and toxicity of the new anticancer candidates and diagnostics for hepatocellular carcinoma (HCC). Here, novel 3D‐liver spheroid models are constructed from human hepatoma cells (HepG2)/ immortalized human hepatocyte‐like cells (imHCs) with primary hepatic stellate cells (HSCs) coculture using the ultralow attachment technique. Spheroid morphology, HSC distribution, metabolic activity, protein expressions, and drug penetration are evaluated. All developed 3D spheroid models exhibit in spherical shape with narrow size distribution, diameter between 639–743 (HepG2‐10%HSC) and 519–631 (imHC‐10%HSC) µm. Both imHC mono and coculture models significantly express normal liver biomarkers at the higher level than HepG2 models. While 3D‐HepG2 models significantly exhibit HCC biomarkers at the higher level than imHC models. HepG2 and imHC spheroids express basal cytochrom P450 (CYP450) enzymes at different levels depending on cell types, culture period, and ratio of coculture. Their metabolic activities for dextromethorphan (CYP2D6) tolbutamide (CYP2C9) and midazolam (CYP3A4) are routinely evaluated. For midazolam metabolism, imHC models allow the detection of phase II metabolic enzymes (UGT2B4 and UGT2B7). The presence of HSC in HepG2‐HSC model increases biological barrier for doxorubicin (DOX) penetration, and escalates IC 50 of DOX from 61.4 to 127.2 µg mL −1 .

Hepatocellular carcinoma (HCC), accounting for 85% of liver cancer cases, continues to be the third leading cause of cancer-related deaths worldwide. Although various forms of chemotherapy and immunotherapy have been investigated in clinics, patients continue to suffer from high toxicity and undesirable side effects. Medicinal plants contain novel critical bioactives that can target multimodal oncogenic pathways; however, their clinical translation is often challenged due to poor aqueous solubility, low cellular uptake, and poor bioavailability. Nanoparticle-based drug delivery presents great opportunities in HCC therapy by increasing selectivity and transferring sufficient doses of bioactives to tumor areas with minimal damage to adjacent healthy cells. In fact, many phytochemicals encapsulated in FDA-approved nanocarriers have demonstrated the ability to modulate the tumor microenvironment. In this review, information about the mechanisms of promising plant bioactives against HCC is discussed and compared. Their benefits and risks as future nanotherapeutics are underscored. Nanocarriers that have been employed to encapsulate both pure bioactives and crude extracts for application in various HCC models are examined and compared. Finally, the current limitations in nanocarrier design, challenges related to the HCC microenvironment, and future opportunities are also discussed for the clinical translation of plant-based nanomedicines from bench to bedside.

Bone cancer has traditionally been treated using surgery, radiotherapy, and/or chemotherapy. The nonspecific distribution of chemotherapy and implantable infections are significant risk factors for the failure of the bone to heal. Multifunctional zinc and silver co-doped bioactive glass nanoparticles (yAg–xZn-BGNPs) with a diameter of 150 ± 30 nm were successfully synthesized using modified sol–gel and two-step post-functionalization processes, tailored to provide antibacterial and anticancer activity whilst maintaining osteogenesis ability. Co-doped BGNPs with Zn and Ag did not significantly alter physicochemical properties, including size, morphology, glass network, and amorphous nature. Apatite-like layer was observed on the surface of yAg–xZn-BGNPs and resorbed in the simulated body fluid solution, which could increase their bioactivity. Human fetal osteoblast cell line (hFOB 1.19) treated with particles showed calcified tissue formation and alkaline phosphatase activity in the absence of osteogenic supplements in vitro, especially with 0.5Ag–1Zn-BGNPs. Moreover, these particles preferentially disrupted the metabolic activity of bone cancer cells (MG-63) and had an antibacterial effect against B. subtilis, E. coli, and S. aureus via the disc diffusion method. This novel 0.5Ag–1Zn-BGNP and 1Ag–1Zn-BGNPs, with wide-ranging ability to stimulate bone regeneration, to inhibit bone cancer cell proliferation, and to prevent bacterial growth properties, may provide a feasible strategy for bone cancer treatment. The 0.5Ag–1Zn-BGNPs and 1Ag–1Zn-BGNPs can be applied for the preparation of scaffolds or filler composites using in bone tissue engineering.

To overcome the scarcity of primary human alveolar epithelial cells for lung research, and the limitations of current cell lines to recapitulate the phenotype, functional and molecular characteristics of the healthy human alveolar epithelium, we have developed a new method to immortalise primary human alveolar epithelial lung cells using a non-viral vector to transfect the telomerase catalytic subunit (hTERT) and the simian virus 40 large-tumour antigen (SV40). Twelve strains of immortalised cells (ICs) were generated and characterised using molecular, immunochemical and morphological techniques. Cell proliferation and sensitivity to polystyrene nanoparticles (PS) were evaluated. ICs expressed caveolin-1, podoplanin and receptor for advanced glycation end-products (RAGE), and most cells were negative for alkaline phosphatase staining, indicating characteristics of AT1-like cells. However, most strains also contained some cells that expressed pro-surfactant protein C, classically described to be expressed only by AT2 cells. Thus, the ICs mimic the cellular heterogeneity in the human alveolar epithelium. These ICs can be passaged, replicate rapidly and remain confluent beyond 15 days. ICs showed differential sensitivity to positive and negatively charged PS nanoparticles, illustrating their potential value as an in vitro model to study respiratory bioreactivity. These novel ICs offer a unique resource to study human alveolar epithelial biology.

Background: The toxicity of inhaled silver nanoparticles on contractile and pro-inflammatory airway smooth muscle cells (ASMCs) that control airway calibre is unknown. We explored the oxidative activities and sulfidation processes of the toxic-inflammatory response. Method: Silver nanospheres (AgNSs) of 20 nm and 50 nm diameter and silver nanowires (AgNWs), short S-AgNWs, 1.5 μm and long L-AgNWs, 10 μm, both 72 nm in diameter were manufactured. We measured their effects on cell proliferation, mitochondrial reactive oxygen species (ROS) release and membrane potential, and also performed electron microscopic studies. Main results and findings: The greatest effects were observed for the smallest particles with the highest specific surface area and greatest solubility that were avidly internalised. ASMCs exposed to 20 nm AgNSs (25 μg mL-1) for 72 hours exhibited a significant decrease in DNA incorporation (-72.4%; p < 0.05), whereas neither the 50 nm AgNSs nor the s-AgNWs altered DNA synthesis or viability. There was a small reduction in ASMC proliferation for the smaller AgNS, although Ag+ at 25 μL mL-1 reduced DNA synthesis by 93.3% (p < 0.001). Mitochondrial potential was reduced by both Ag+ (25 μg mL-1) by 47.1% and 20 nm Ag NSs (25 μg mL-1) by 40.1% (*both at p < 0.05), but was not affected by 50 nm AgNSs and the AgNWs. None of the samples showed a change in ROS toxicity. However, malondialdehyde release, associated with greater total ROS, was observed for all AgNPs, to an extent following the geometric size (20 nm AgNS: 213%, p < 0.01; 50 nm AgNS: 179.5%, p < 0.01 and L-AgNWs by 156.2%, p < 0.05). The antioxidant, N-acetylcysteine, prevented the reduction in mitochondrial potential caused by 20 nm AgNSs. The smaller nanostructures were internalised and dissolved within the ASMCs with the formation of non-reactive silver sulphide (Ag2S) on their surface, but with very little uptake of L-AgNWs. When ASMCs were incubated with H2S-producing enzyme inhibitors, the spatial extent of Ag2S formation was much greater. Conclusion: The intracellular toxicity of AgNPs in ASMCs is determined by the solubility of Ag+ released and the sulfidation process, effects related to particle size and geometry. Passivation through sulfidation driven by biogenic H2S can outcompete dissolution, thus reducing the toxicity of the smaller intracellular Ag nanostructures.

Endoscopy is the gold standard investigation in the diagnosis of gastrointestinal cancers and the management of early and pre-malignant lesions either by resection or ablation. Recently gold nanoparticles have shown promise in cancer diagnosis and therapeutics (theranostics). The combination of multifunctional gold nanoparticles with near infrared fluorescence endoscopy for accurate mapping of early or pre-malignant lesions can potentially enhance diagnostic efficiency while precisely directing endoscopic near infrared photothermal therapy for established cancers. The integration of endoscopy with near infrared fluorescence imaging and photothermal therapy was aided by the accumulation of our multifunctionalized PEG-GNR-Cy5.5-anti-EGFR-antibody gold nanorods within gastrointestinal tumor xenografts in BALB/c mice. Control mice (with tumors) received either gold nanorods or photothermal therapy, while study mice received both treatment modalities. Local (tumor-centric) and systemic effects were examined for 30 days. Clear endoscopic near infrared fluorescence signals were observed emanating specifically from tumor sites and these corresponded precisely to the tumor margins. Endoscopic fluorescence-guided near infrared photothermal therapy successfully induced tumor ablations in all 20 mice studied, with complete histological clearance and minimal collateral damage. Multi-source analysis from histology, electron microscopy, mass spectrometry, blood, clinical evaluation, psychosocial and weight monitoring demonstrated the inherent safety of this technology. The combination of this innovative nanotechnology with gold standard clinical practice will be of value in enhancing the early optical detection of gastrointestinal cancers and a useful adjunct for its therapy.

There are no methods sensitive enough to detect enzymes within cells, without the use of analyte labeling. Here we show that it is possible to detect protein ion signals of three different H2S-synthesizing enzymes inside microglia after pretreatment with silver nanowires (AgNW) using time-of-flight secondary ion mass spectrometry (TOF-SIMS). Protein fragment ions, including the fragment of amino acid (C4H8N+ = 70 amu), fragments of the sulfur-producing cystathionine-containing enzymes, and the Ag+ ion signal could be detected without the use of any labels; the cells were mapped using the C4H8N+ amino acid fragment. Scanning electron microscopy imaging and energy-dispersive X-ray chemical analysis showed that the AgNWs were inside the same cells imaged by TOF-SIMS and transformed chemically into crystalline Ag2S within cells in which the sulfur-producing proteins were detected. The presence of these sulfur-producing cystathionine-containing enzymes within the cells was confirmed by Western blots and confocal microscopy images of fluorescently labeled antibodies against the sulfur-producing enzymes. Label-free TOF-SIMS is very promising for the label-free identification of H2S-contributing enzymes and their cellular localization in biological systems. The technique could in the future be used to identify which of these enzymes are most contributory.

Sensitive detection of disease biomarkers expressed by human cells is critical to the development of novel diagnostic and therapeutic methods. Here we report that plasmonic arrays based on gold nanostar (AuNS) monolayers enable up to 19-fold fluorescence enhancement for cellular imaging in the near-infrared (NIR) biological window, allowing the application of low quantum yield fluorophores for sensitive cellular imaging. The high fluorescence enhancement together with low autofluorescence interference in this wavelength range enable higher signal-to-noise ratio compared to other diagnostic modalities. Using AuNSs of different geometries and therefore controllable electric field enhancement, cellular imaging with tunable enhancement factors is achieved, which may be useful for the development of multicolour and multiplexed platforms for a panel of biomarkers, allowing to distinguish different subcell populations at the single cell level. Finally, the uptake of AuNSs within HeLa cells and their high biocompatibility, pave the way for novel high-performance in vitro and in vivo diagnostic platforms.

There is a need for novel strategies to treat aggressive breast cancer subtypes and overcome drug resistance. ZnO nanoparticles (NPs) have potential in cancer therapy due to their ability to potently and selectively induce cancer cell apoptosis. Here, we tested the in vitro chemotherapeutic efficacy of ZnONPs loaded via a mesoporous silica nanolayer (MSN) towards drug-sensitive breast cancer cells (MCF-7: estrogen receptor-positive, CAL51: triple-negative) and their drug-resistant counterparts (MCF-7TX, CALDOX). ZnO-MSNs were coated on to gold nanostars (AuNSs) for future imaging capabilities in the NIR-II range. Electron and confocal microscopy showed that MSN-ZnO-AuNSs accumulated close to the plasma membrane and were internalized by cells. High-resolution electron microscopy showed that MSN coating degraded outside the cells, releasing ZnONPs that interacted with cell membranes. MSN-ZnO-AuNSs efficiently reduced the viability of all cell lines, and CAL51/CALDOX cells were more susceptible than MCF7/MCF-7-TX cells. MSN-ZnO-AuNSs were then conjugated with the antibody to Frizzled-7 (FZD-7), the receptor upregulated by several breast cancer cells. We used the disulphide (S-S) linker that could be cleaved with a high concentration of glutathione normally observed within cancer cells, releasing Zn2+ into the cytoplasm. FZD-7 targeting resulted in approximately three-fold amplified toxicity of MSN-ZnO-AuNSs towards the MCF-7TX drug-resistant cell line with the highest FZD-7 expression. This study shows that ZnO-MSs are promising tools to treat triple-negative and drug-resistant breast cancers and highlights the potential clinical utility of FZD-7 for delivery of nanomedicines and imaging probes specifically to these cancer types.

Gold nanorods (GNRs) are increasingly being investigated for cancer theranostics as they possess features which lend themselves in equal measures as contrast agents and catalysts for photothermal therapy. Their optical absorption spectral peak wavelength is determined by their size and shape. Photothermal therapy using GNRs is typically established using near infrared light as this allows sufficient penetration into the tumour matrix. Continuous wave (CW) lasers are the most commonly applied source of near infrared irradiation on GNRs for tumour photothermal therapy. It is perceived that large tumours may require fractionated or prolonged irradiation. However the true efficacy of repeated or protracted CW irradiation on tumour sites using the original sample of GNRs remains unclear. In this study spectroscopy and transmission electron microscopy are used to demonstrate that GNRs reshape both in vitro and in vivo after CW irradiation, which reduces their absorption efficiency. These changes were sustained throughout and beyond the initial period of irradiation, resulting from a spectral blue-shift and a considerable diminution in the absorption peak of GNRs. Solid subcutaneous tumours in immunodeficient BALB/c mice were subjected to GNRs and analysed with electron microscopy pre- and post-CW laser irradiation. This phenomenon of thermally induced GNR reshaping can occur at relatively low bulk temperatures, well below the bulk melting point of gold. Photoacoustic monitoring of GNR reshaping is also evaluated as a potential clinical aid to determine GNR absorption and reshaping during photothermal therapy. Aggregation of particles was coincidentally observed following CW irradiation, which would further diminish the subsequent optical absorption capacity of irradiated GNRs. It is thus established that sequential or prolonged applications of CW laser will not confer any additional photothermal effect on tumours due to significant attenuations in the peak optical absorption properties of GNRs following primary laser irradiation.