Biosynthesis of palladium, platinum, and their bimetallic nanoparticles using rosemary and ginseng herbal plants: evaluation of anticancer activity.

In this research, palladium (II) and platinum (II), as well as their bimetallic nanoparticles were synthesized using medicinal plants in an eco-friendly manner. Rosemary and Ginseng extracts were chosen due to their promising anticancer potential. The synthesized nanoparticles underwent characterization through FT-IR spectroscopy, DLS, XRD, EDX, SEM, and TEM techniques. Once the expected structures were confirmed, the performance of these nanoparticles, which exhibited an optimal size, was evaluated as potential anticancer agents through in vitro method on colon cancer cell lines (Ls180, SW480). MTT assay studies showed that the synthesized nanoparticles induced cell death. Moreover, real-time PCR was employed to investigate autophagy markers and the effect of nanoparticles on the apoptosis process, demonstrating a significant effect of the synthesized compounds in this regard.

Antitumor potential of platinum(II) complexes of selenium donor ligands.

Platinum(II) coordination compounds are widely applied in clinics as anticancer drugs. In this review, we provide a summary of the reports on cytotoxic properties of platinum(II) complexes of selenium donor ligands along with a brief description of their structural features. It has been observed that the platinum(II) complexes of selenones and selenoethers display reasonable antitumor properties and in some cases their cytotoxic activity is greater than cisplatin. The complexes containing NH3 ligands along with selenones were found to exhibit better cytotoxicity compared to the binary Pt-selenone complexes. The mechanistic insights showed that these complexes exert antitumor activity through reactive oxygen species (ROS) generation and induction of apoptosis. The platinum-selenoether coordination compounds can self-assemble into spherical aggregates capable of self-delivery. The self-assembled Pt-selenium aggregates induce cell apoptosis via ROS, which leads to high selectivity between cancer cells and normal cells in cytotoxicity assays.

Targeting critical pathways in ferroptosis and enhancing antitumor therapy of Platinum drugs for colorectal cancer.

Colorectal cancer (CRC) can be resistant to platinum drugs, possibly through ferroptosis suppression, albeit the need for further work to completely understand this mechanism. This work aimed to sum up current findings pertaining to oxaliplatin resistance (OR) or resistance to ascertain the potential of ferroptosis to regulate oxaliplatin effects. In this review, tumor development relating to iron homeostasis, which includes levels of iron that ascertain cells' sensitivity to ferroptosis, oxidative stress, or lipid peroxidation in colorectal tumor cells that are connected with ferroptosis initiation, especially the role of c-Myc/NRF2 signaling in regulating iron homeostasis, coupled with NRF2/GPX4-mediated ferroptosis are discussed. Importantly, ferroptosis plays a key role in OR and ferroptotic induction may substantially reverse OR in CRC cells, which in turn could inhibit the imbalance of intracellular redox induced by oxaliplatin and ferroptosis, as well as cause chemotherapeutic resistance in CRC. Furthermore, fundamental research of small molecules, ferroptosis inducers, GPX4 inhibitors, or natural products for OR coupled with their clinical applications in CRC have also been summarized. Also, potential molecular targets and mechanisms of small molecules or drugs are discussed as well. Suggestively, OR of CRC cells could significantly be reversed by ferroptosis induction, wherein this result is discussed in the current review. Prospectively, the existing literature discussed in this review will provide a solid foundation for scientists to research the potential use of combined anticancer drugs which can overcome OR via targeting various mechanisms of ferroptosis. Especially, promising therapeutic strategies, challenges ,and opportunities for CRC therapy will be discussed.

Albumin-templated platinum (II) sulfide nanodots for size-dependent cancer theranostics.

Transition-metal chalcogenides, such as noble metal chalcogenides, hold tremendous potential as efficient agents for photo-induced cancer theranostics due to their unique physicochemical properties. However, a critical bottleneck still lies in exploring simple and controllable methods to synthesize noble metal chalcogenides especially PtS for in vivo photo-induced cancer imaging and simultaneous therapy. Herein, we proposed the albumin-templated synthesis of size-controllable platinum (II) sulfide nanodots (PtS-NDs) for multimodal cancer imaging and potent photothermal therapy. PtS-NDs were precisely synthesized with a tunable size ranging from 2.1 nm to 4.5 nm through a thermodynamically controlled growth inside albumin nanocages. PtS-NDs yielded significant near-infrared (NIR) absorbance and outstanding photothermal conversion under NIR laser irradiation, as well as effective resistance to photobleaching, thereby generating remarkable in vivo photoacoustic signals and distinct hyperthermia at tumor site. Moreover, these nanodots possessed efficient cellular uptake and tumor targeting capabilities in a size-dependent manner, thus leading to controllable diagnostic and thermo-therapeutic efficacy. Specifically, PtS-NDs with core diameter of 4.5 nm displayed preferable in vivo photoacoustic and CT imaging with high sensitivity, spatially and anatomically enhanced imaging contrast, together with hyperthermia mediated tumor ablation. Thus, the albumin-templated biomimetic synthesis provided an insightful strategy on fabricating theranostic PtS-NDs for potential clinical applications. STATEMENT OF SIGNIFICANCE: Noble metal chalcogenides especially PtS are of particular importance in the field of precise nanomedicine to improve both accuracy of cancer diagnosis and efficiency of tumor treatment. However, the intensively preclinical investigation of PtS was limited due to the lack of simple and controllable synthetic methods. Here, we report an albumin-templated biomineralization synthesis of platinum (II) sulfide nanodots (PtS-NDs). Specifically, albumin-templated biomineralization of PtS-NDs was induced by the electrostatic interactions between albumin and Pt2+, followed by the nucleation and growth inside the albumin nanocages. The resulting PtS-NDs showed good dispersibility and biosafety, as well as size-dependent photophysical properties and biological behaviors. Therefore, albumin-based biomineralization is a promising and safe strategy to facilely fabricate Pt-based chalcogenide for tumor theranostics.

Yolk-shell Fe3O4@Carbon@Platinum-Chlorin e6 nanozyme for MRI-assisted synergistic catalytic-photodynamic-photothermal tumor therapy.

HYPOTHESIS: Tumor treatments based on phototherapy, such as photodynamic therapy (PDT) and photothermal therapy (PTT), are promising anticancer strategies. However, their dependence on light also poses several limitations for their application. Therefore, the establishment of a multifunctional nanotheranostic platform based on light therapy is needed to improve applicability of the technology. EXPERIMENTS: We designed yolk-shell magnetic Fe3O4@Carbon@Platinum-Chlorin e6 nanoparticles (MCPtCe6), which may be used for Magnetic resonance imaging (MRI) and synergistic catalytic-photodynamic-photothermal (catalytic-PDT-PTT) tumor therapy. FINDINGS: We designed to compound multiple nanozymes and solve the drawbacks of single nanozyme and give additional functionalization to nanozymes for tumor therapy. Fe3O4 has T2 weighted MRI ability. The designed yolk-shell structure can disperse Fe3O4 in the carbon shell layer, which in turn can act as a carrier for PtNPs and improve the dispersion of both Fe3O4 and Pt. Pt nanoparticles attached to the surface of N-doped carbon spheres enhanced the catalytic ability of the nanozyme to generate reactive oxygen species (ROS). The covalently linked photosensitizer chlorin e6 (Ce6) on the Fe3O4@C@Pt (MCPt) nanozyme is essential for the therapeutic effects of PDT. MCPtCe6 can be specifically activated by the microenvironment through an enzyme-like catalytic process and extend PDT/PTT in acidic and H2O2-rich microenvironments. The results showed that MCPtCe6 had a high photothermal conversion efficiency (η = 28.28%), indicating its feasibility for PTT. Further cellular and animal studies have revealed that catalytic-PDT-PTT therapy can effectively inhibit tumors both in vitro and in vivo.

Alantolactone-Loaded Pegylated Prodrug Nanocarriers for Synergistic Treatment of Cisplatin-Resistant Ovarian Cancer via Reactivating Mitochondrial Apoptotic Pathway.

Ovarian cancer (OV) seriously damages women's health because of refractory OV and the development of platinum (Pt) resistance. New treatment strategies are urgently needed to deal with the treatment of cisplatin-resistant OV. Here, a reduction-sensitive pegylated Pt(IV) prodrug was synthesized by amidation of methoxy polyethylene glycol amine (PEG750-NH2) with monocarboxylic Pt(IV) prodrug (Pt(IV)-COOH). Then alantolactone (AL) loaded PEG-Pt(IV) nanocarriers (NP(Pt)@AL) were prepared. In the cisplatin-resistant model of OV, cancer cells actively ingest NP(Pt)@AL through endocytosis, and AL and Pt(II) were disintegrated and released under high intracellular reductant condition. The activity of thioredoxin reductase 1 (TrxR1) inhibited by AL and the adducts of Pt(II) with mitochondrial DNA (mDNA) can costimulate reactive oxygen species (ROS) and reactivate the mitochondrial pathway of apoptosis. Meanwhile, Pt(II) binds with nuclear DNA (nDNA) to jointly promote cell apoptosis. Both in vitro and in vivo results demonstrated that NP(Pt)@AL could effectively reverse the drug resistance and displayed excellent synergistic therapeutic efficacy on platinum-resistant OV with high safety. Therefore, reactivation of the mitochondrial pathway of apoptosis would be a potential strategy to improve the therapeutic effect of Pt-based chemotherapy and even reverse drug resistance.

Safety and efficacy of the tumor-selective adenovirus enadenotucirev with or without paclitaxel in platinum-resistant ovarian cancer: a phase 1 clinical trial.

BACKGROUND: Treatment outcomes remain poor in recurrent platinum-resistant ovarian cancer. Enadenotucirev, a tumor-selective and blood stable adenoviral vector, has demonstrated a manageable safety profile in phase 1 studies in epithelial solid tumors. METHODS: We conducted a multicenter, open-label, phase 1 dose-escalation and dose-expansion study (OCTAVE) to assess enadenotucirev plus paclitaxel in patients with platinum-resistant epithelial ovarian cancer. During phase 1a, the maximum tolerated dose of intraperitoneally administered enadenotucirev monotherapy (three doses; days 1, 8 and 15) was assessed using a 3+3 dose-escalation model. Phase 1b included a dose-escalation and an intravenous dosing dose-expansion phase assessing enadenotucirev plus paclitaxel. For phase 1a/b, the primary objective was to determine the maximum tolerated dose of enadenotucirev (with paclitaxel in phase 1b). In the dose-expansion phase, the primary endpoint was progression-free survival (PFS). Additional endpoints included response rate and T-cell infiltration. RESULTS: Overall, 38 heavily pretreated patients were enrolled and treated. No dose-limiting toxicities were observed at any doses. However, frequent catheter complications led to the discontinuation of intraperitoneal dosing during phase 1b. Intravenous enadenotucirev (1×1012 viral particles; days 1, 3 and 5 every 28-days for two cycles) plus paclitaxel (80 mg/m2; days 9, 16 and 23 of each cycle) was thus selected for dose-expansion. Overall, 24/38 (63%) patients experienced at least 1 Grade ≥3 treatment-emergent adverse event (TEAE); most frequently neutropenia (21%). Six patients discontinued treatment due to TEAEs, including one patient due to a grade 2 treatment-emergent serious AE of catheter site infection (intraperitoneal enadenotucirev monotherapy). Among the 20 patients who received intravenous enadenotucirev plus paclitaxel, 4-month PFS rate was 64% (median 6.2 months), objective response rate was 10%, 35% of patients achieved stable disease and 65% of patients had a reduction in target lesion burden at ≥1 time point. Five out of six patients with matched pre-treatment and post-treatment biopsies treated with intravenous enadenotucirev plus paclitaxel had increased (mean 3.1-fold) infiltration of CD8 +T cells in post-treatment biopsies. CONCLUSIONS: Intravenously dosed enadenotucirev plus paclitaxel demonstrated manageable tolerability, an encouraging median PFS and increased tumor immune-cell infiltration in platinum-resistant ovarian cancer. TRIAL REGISTRATION NUMBER: NCT02028117.

Traditional herbal medicine combined with first-line platinum-based chemotherapy for advanced non-small-cell lung cancer: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is a major health burden in many countries. This review aimed to evaluate the efficacy of traditional herbal medicine (THM) combined with first-line platinum-based chemotherapy (PBCT) for the treatment of advanced NSCLC. METHODS: From inception to April 2021, relevant studies were retrieved from 9 electronic databases. Randomized controlled trials (RCTs) comparing survival outcomes of THM + PBCT treatment with PBCT treatment in patients with advanced NSCLC were reviewed. The risk of bias was evaluated using the Cochrane Risk of Bias Tool. Overall survival, 1-year survival, progression-free survival or time to progression, tumor response rate, and adverse effects were analyzed. RESULTS: Sixteen RCTs comprising 1445 patients were included. The meta-analysis indicated that THM + PBCT treatment, compared to PBCT alone, could improve overall survival (median survival ratio = 1.24, 95% confidence intervals [CI] [1.11, 1.39], P < .001), progression-free survival/time to progression (median survival ratio = 1.22, 95% CI [1.09, 1.37], P < .001), and the 1-year survival rate (risk ratio [RR] = 1.56, 95% CI [1.31, 1.86], P < .001). THM + PBCT also led to a higher tumor response rate (RR = 1.39, 95% CI [1.22, 1.59], P < .001) and lower incidence of thrombocytopenia (RR = 0.72, 95% CI [0.56, 0.92], P = .009) and nausea/vomiting (RR = 0.35, 95% CI [0.21, 0.57], P < .001), while there was no significant effect observed on leukopenia (RR = 0.68, 95% CI [0.34, 1.36], P = .27). CONCLUSION: THM, when used in combination with PBCT, might increase survival and the tumor response rate while decreasing the side effects caused by chemotherapy in patients with advanced NSCLC. However, considering the limited methodological qualities of the included trials, more rigorous RCTs are needed.

Carcinostatic effects of alkanoyl ascorbate plus platinum nano-colloid and stabilization of the esterolytically resultant ascorbate by hydrogen.

Carcinostatic effects of combined use of ascorbic acid (Asc), 2-O-phospho- or 6-O-palmitoyl ascorbate (Asc2Phos, Asc6Palm) or diverse alkanoyl Asc, and nano-sized platinum-poly(N-vinyl-pyrrolidone) colloid (PVP-Pt; 2-nm diameter) were examined on human esophagus carcinoma-derived cells KYSE70. Cell viability was repressed by 'Asc6Palm + PVP-Pt' mixture more markedly than by Asc6Palm or PVP-Pt alone, together with cell shrinkage and fragmentation, in contrast to no additive carcinostatic effect of 'Asc + PVP-Pt' or 'Asc2Phos + PVP-Pt'. The effects might be partly due to efficiency for intracellular uptake of PVP-Pt, as previously shown by our studies that Pt atoms composed of PVP-Pt were incorporated into human tongue carcinoma cells by 9.6-fold compared to normal human tongue epitheliocytes. Asc6Palm was advantageous for intracellular uptake, in terms of the proper balance for molecular hydrophilicity-lipophilicity (BMHL), whereas 6-O-stearoyl (C18) Asc or 2,6-O-dipalmitoyl (2 × C16) was demonstrated to be less carcinostatic owing to a lower BMHL. Although esterolytically converted from Asc6Palm, Asc was necessitated to be retained for efficient carcinostasis, and demonstrated by HPLC-coulometric ECD analysis to be appreciably stabilized in electrolytically generated hydrogen (dissolved hydrogen: 0.575 mg/L)-water, but scarcely in hydrogen-gas-bubbled water (0.427 mg/L), Mg stick-derived hydrogen (0.044 mg/L) water, or tap water, suggesting that hydrogen-rich water suppresses oxidative decomposition of Asc. Thus, Asc6Palm plus PVP-Pt with hydrogen-rich water supplement might be applicable for carcinostatic therapy.

Anticancer Properties of Platinum Nanoparticles and Retinoic Acid: Combination Therapy for the Treatment of Human Neuroblastoma Cancer.

Neuroblastoma is the most common extracranial solid tumor in childhood. The different treatments available for neuroblastoma are challenged by high rates of resistance, recurrence, and progression, most notably in advanced cases and highly malignant tumors. Therefore, the development of more targeted therapies, which are biocompatible and without undesired side effects, is highly desirable. The mechanisms of actions of platinum nanoparticles (PtNPs) and retinoic acid (RA) in neuroblastoma have remained unclear. In this study, the anticancer effects of PtNPs and RA on neuroblastoma were assessed. We demonstrated that treatment of SH-SY5Y cells with the combination of PtNPs and RA resulted in improved anticancer effects. The anticancer effects of the two compounds were mediated by cytotoxicity, oxidative stress (OS), mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and apoptosis-associated networks. Cytotoxicity was confirmed by leakage of lactate dehydrogenase (LDH) and intracellular protease, and oxidative stress increased the level of reactive oxygen species (ROS), 4-hydroxynonenal (HNE), malondialdehyde (MDA), and nitric oxide (NO), and protein carbonyl content (PCC). The combination of PtNPs and RA caused mitochondrial dysfunction by decreasing the mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content, number of mitochondria, and expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Endoplasmic reticulum-mediated stress and apoptosis were confirmed by upregulation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), activating transcription factor 4 (ATF4), p53, Bax, and caspase-3 and down regulation of B-cell lymphoma 2 (BCl-2). PtNPs and RA induced apoptosis, and oxidative DNA damage was evident by the accumulation of 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-hydroxyguanosine (8-OHG). Finally, PtNPs and RA increased the differentiation and expression of differentiation markers. Differentiated SH-SY5Y cells pre-treated with PtNPs or RA or the combination of both were more sensitive to the cytotoxic effect of cisplatin than undifferentiated cells. To our knowledge, this is the first study to demonstrate the effect of the combination of PtNPs and RA in neuroblastoma cells. PtNPs may be a potential preconditioning or adjuvant compound in chemotherapeutic treatment. The results of this study provide a rationale for clinical evaluation of the combination of PtNPs and RA for the treatment of children suffering from high-risk neuroblastoma.

A novel theranostic nano-platform (PB@FePt-HA-g-PEG) for tumor chemodynamic-photothermal co-therapy and triple-modal imaging (MR/CT/PI) diagnosis.

The construction of multi-functional oncotherapy nano-platforms combining diagnosis and therapy remains a tough challenge. Prussian blue nano-cubes with optimized particle size were applied as photothermal agents and loaded with FePt NPs, effective ferroptosis agents, on the surface via an in situ reduction strategy. To attain the goal of precise medicine, hyaluronic acid was wrapped around the surface of the nanocomposites (PB@FePt NCs) for highly specific recognition of tumor cells. Finally, we successfully designed and fabricated a nano-agent (PB@FePt-HA-g-PEG NCs) to serve as a versatile nano-platform with both highly specific targeting ability for chemodynamic-photothermal co-therapy and triple-modal imaging (magnetic resonance/computed tomography/photothermal imaging) capability. Via intravenous injection, the as-constructed oncotherapy nano-platform could effectively ablate 4T1 tumor xenografts with excellent biocompatibility for chemodynamic-photothermal co-therapy. In this study we conducted a reasonable exploration to design multi-functional oncotherapy nano-platforms combining multiplexed imaging diagnosis and high therapeutic performance, which provides an innovative paradigm for precision cancer treatment.

A Photocaged, Water-Oxidizing, and Nucleolus-Targeted Pt(IV) Complex with a Distinct Anticancer Mechanism.

Targeted anticancer prodrugs that can be controllably activated are highly desired for personalized precision medicine in cancer therapy. Such prodrugs with unique action modes are also promising to overcome drug resistance. Herein, we report coumaplatin, an oxaliplatin-based and photocaged Pt(IV) prodrug, to realize nuclear accumulation along with "on-demand" activation. This prodrug is based on a Pt(IV) complex that can be efficiently photoactivated via water oxidation without the requirement of a reducing agent. Coumaplatin accumulates very efficiently in the nucleoli, and upon photoactivation, this prodrug exhibits a level of photocytotoxicity up to 2 orders of magnitude higher than that of oxaliplatin. Unexpectedly, this prodrug presents strikingly enhanced tumor penetration ability and utilizes a distinct action mode to overcome drug resistance; i.e., coumaplatin but not oxaliplatin induces cell senescence, p53-independent cell death, and immunogenic cell death along with T cell activation. Our findings not only provide a novel strategy for the rational design of controllably activated and nucleolus-targeted Pt(IV) anticancer prodrugs but also demonstrate that accumulating conventional platinum drugs to the nucleus is a practical way to change its canonical mechanism of action and to achieve reduced resistance.

Platinum-loaded, selenium-doped hydroxyapatite nanoparticles selectively reduce proliferation of prostate and breast cancer cells co-cultured in the presence of stem cells.

Chemotherapeutic treatment of patients with bone tumors or bone metastases often leads to severe side effects such as high drug toxicity, lack of tumor specificity and induced drug resistance. A novel strategy to treat early stages of bone metastases involves local co-delivery of multiple chemotherapeutic agents to synergistically improve the curative effect and overcome shortcomings of traditional chemotherapy. Herein we show that selenite-doped hydroxyapatite nanoparticles loaded with a hydroxyapatite-binding anti-tumor platinum complex (PtPP-HASe) selectively reduce proliferation of cancer cells without reducing proliferation of bone marrow stem cells. These PtPP-HASe particles were nanocrystalline with selenium (Se) and platinum (Pt) contents ranging between 0-10 and 1.5-3 wt%, respectively. Release kinetics of Se and Pt from PtPP-HASe nanoparticles resulted in a cumulative release of ∼10 and ∼66 wt% after 7 days, respectively. At a Pt/Se ratio of 8, released Pt and Se species selectively reduced cell number of human prostate (PC3) and human breast cancer cells (MDA-MB-231) by a factor of >10 with limited effects on co-cultured human bone marrow stem cells (hBMSc). These novel nanoparticles demonstrate high anti-cancer selectivity, which offers ample opportunities for the design of novel biomaterials with potent and selective chemotherapeutic efficacy against cancer cells.

Novel Silver-Platinum Nanoparticles for Anticancer and Antimicrobial Applications.

BACKGROUND: Cancer is a disease with an enormous worldwide impact. One of the fatal complications in cancer patients are bacterial opportunistic infections. The use of chemotherapeutic drugs made cancer remission more frequent and prolonged patient survival, but, increased the risk of infections. PURPOSE: Address the current problem with growing pandemic cancer and considering high risks of complications with bacterial infections, the present study synthesized novel dendritic assembly of silver (Ag)-platinum (Pt) nanoparticles. METHODS: Nanoparticles were characterized by TEM analysis, and the composition was confirmed by EDX. Bacterial studies were performed for Gram-positive Staphylococcus aureus, Gram-negative Pseudomonas aeruginosa and Gram-negative multi-drug resistant Escherichia coli. Cell experiments were performed with two different cancer cell lines, glioblastoma and melanoma to determine anticancer activity. Finally, cytotoxicity with fibroblast was tested. RESULTS: The TEM analysis of silver-platinum (AgPt) nanoparticles showed dendrimer shape nanoparticles with a mean size of 42 ± 11nm. Elemental composition was analyzed by EDX, confirming the presence of both Ag and Pt metals. The synthesized nanoparticles significantly inhibited the growth of medically important pathogenic, Gram-positive Staphylococcus aureus, Gram-negative Pseudomonas aeruginosa and Gram-negative multi-drug resistant Escherichia coli. Bactericidal effect of AgPt nanoparticles had greater effectiveness than silver nanoparticles. MTS assay revealed a selective and dose-dependent anticancer activity of AgPt nanoparticles over cancer cell lines glioblastoma and melanoma in the 10-250 µg/mL concentration range. Cytotoxicity experiments with fibroblast cells showed no side effects of nanoparticles against healthy cells at a range of concentrations from 10-50 µg/mL. CONCLUSION: The newly synthesized AgPt nanoparticles have a promising future as a potent anticancer agent with antibacterial properties.

Ultrasound-Switchable Nanozyme Augments Sonodynamic Therapy against Multidrug-Resistant Bacterial Infection.

Ultrasound (US)-driven sonodynamic therapy (SDT) has demonstrated wide application prospects in the eradication of deep-seated bacterial infections due to its noninvasiveness, site-confined irradiation, and high-tissue-penetrating capability. However, the ineffective accumulation of sonosensitizers at the infection site, the hypoxic microenvironment, as well as rapid depletion of oxygen during SDT greatly hamper the therapeutic efficacy of SDT. Herein, an US-switchable nanozyme system was proposed for the controllable generation of catalytic oxygen and sonosensitizer-mediated reactive oxygen species during ultrasound activation, thereby alleviating the hypoxia-associated barrier and augmenting SDT efficacy. This nanoplatform (Pd@Pt-T790) was easily prepared by bridging enzyme-catalytic Pd@Pt nanoplates with the organic sonosensitizer meso-tetra(4-carboxyphenyl)porphine (T790). It was really interesting to find that the modification of T790 onto Pd@Pt could significantly block the catalase-like activity of Pd@Pt, whereas upon US irradiation, the nanozyme activity was effectively recovered to catalyze the decomposition of endogenous H2O2 into O2. Such "blocking and activating" enzyme activity was particularly important for decreasing the potential toxicity and side effects of nanozymes on normal tissues and has potential to realize active, controllable, and disease-loci-specific nanozyme catalytic behavior. Taking advantage of this US-switchable enzyme activity, outstanding accumulation in infection sites, as well as excellent biocompatibility, the Pd@Pt-T790-based SDT nanosystem was successfully applied to eradicate methicillin-resistant Staphylococcus aureus (MRSA)-induced myositis, and the sonodynamic therapeutic progression was noninvasively monitored by photoacoustic imaging and magnetic resonance imaging. The developed US-switchable nanoenzyme system provides a promising strategy for augmenting sonodynamic eradication of deep-seated bacterial infection actively, controllably, and precisely.

The assembly and antitumor activity of lycium barbarum polysaccharide-platinum-based conjugates.

In this work, the new polysaccharide-platinum conjugates of 5-aminosalicylic acid modified lycium barbarum polysaccharide linking platinum compounds were designed in order to construct an anticancer metal drug delivery system. The multiple analysis methods were used to describe the chemical structure and physical properties of the polysaccharide-metal conjugates. The results showed that 5-aminosalicylic acid successfully acted as linker which was covalently bound between polysaccharide and platinum compound. The morphology and rheological properties of polysaccharide have been changed by the formation of conjugates, which exhibited certain inhibition specificity to A549 (human lung cancer cell line). The agarose gel electrophoresis and fluorescence microscopy results demonstrated that such conjugates promoted the unwinding of DNA and could significantly damage the nucleus of A549 cells. Cell cycle analyzing the Pt complex of conjugates could cause intracellular DNA damage and induced G2 phase arrest. So, polysaccharide-platinum conjugates might find a range of applications, for example in metal anticancer drug delivery.

Platinum-gold nanoraspberries as effective photosensitizer in anticancer photothermal therapy.

BACKGROUND: New nanophotosensitizers for photothermal cancer therapy (PTT) are still sought. In this paper we propose fancy shaped, non agglomerated core/shell PtAu NRs nanoraspberries (PtAu NRs) as potential nanophotosensitizers in PTT. RESULTS: Light microscopy images of two colon cancer cell lines (SW480, SW620) showed, that the laser irradiation combined with PtAu NRs caused visible changes in the cell morphology. Fourier Transform InfraRed (FTIR) and Raman spectroscopies showed chemical changes in the DNA, phospholipids, lipids and protein structures caused by laser irradiation in the presence of PtAu NRs. The MTS assay showed ~ 25% mortality of cancer cells due to the addition of PtAu NRs to the cell culture, while for laser irradiation combined with nanoparticles, the mortality of cancer cells increased to 65% for the 650 nm laser and to 60% for the 808 nm laser. The calculated photothermal conversion efficiency reached 62% and 51% for the 650 nm and 808 nm lasers, respectively. CONCLUSIONS: PtAu NRs could be applied as effective light-absorbers in the PTT anticancer therapy.

Enhanced melanoma cell-killing by combined phototherapy/radiotherapy using a mesoporous platinum nanostructure.

BACKGROUND: Metal nanomaterials have a significant potential as photosensitizer and radiosensitizer. The purpose of this study was to evaluate the cytotoxicity of a platinum mesoporous nanostructure (Pt MN) toward a melanoma cancer cell line upon combined laser radiation (808 nm, 1 and 1.5 W cm-2) and X-ray irradiation (6 MV, 2, 4, and 6 Gy). METHODS: Pt MN was synthesized by a simple procedure and characterized by field emission scanning and transmission electron microscopy. A mouse malignant melanoma cell line C540 (B16/F10) was treated with Pt MN, laser light and/or X-ray. RESULTS: Pt MN had a mesoporous structure with a sponge-resemble shape comprised of ensembles of very small adhered particles of <11 nm and about 5-nm pores. While Pt MN represented a low toxicity toward and considerable uptake into the cell line in a concentration range of 10-100 µg mL-1, laser light radiation alone was also not toxic, and X-ray irradiation alone induced a limited toxicity, Pt MN was toxic against the cells in a dose dependent manner upon laser light radiation, X-ray irradiation, or their combined exposure. The killing efficacy of Pt MN upon X-ray irradiation was more obvious at 72 h post-treatment. The combined exposure (laser radiation followed by X-ray irradiation) led to a deep cell killing and a very low melanoma cell viability (∼1%). Significant melanoma cancer cell killing of Pt MN was due to reactive oxygen species (ROS) production upon combined exposure of laser and X-ray, while cell killing upon laser light radiation was due to heat generation. CONCLUSION: Pt MN was introduced as a supreme laser/X-ray sensitizer for treatment of cancer with a high ability to produce ROS and a potent impact on decreasing cell viability.

Tumor microenvironment responsive FePt/MoS2 nanocomposites with chemotherapy and photothermal therapy for enhancing cancer immunotherapy.

The metastasis and recurrence of tumors are the main reasons for cancer death. In this work, a promising therapy for tumor treatment that can eliminate primary tumors and prevent tumor relapses is introduced by combining chemotherapy, photothermal therapy (PTT) and immunotherapy. Multifunctional FePt/MoS2-FA nanocomposites (FPMF NCs) were obtained via anchoring FePt nanoparticles and folic acid (FA) on MoS2 nanosheets. As an efficient ferroptosis agent, FePt nanoparticles could catalyze the Fenton reaction to produce the reactive oxygen species (ROS). Through the highly effective photothermal conversion of MoS2 nanosheets, the primary tumor cells could be ablated by photothermal therapy (PTT). Moreover, the metastatic tumors were eliminated effectively with the help of oligodeoxynucleotides containing cytosine-guanine (CpG ODNs) combined with systemic checkpoint blockade therapy using an anti-CTLA4 antibody. Even more intriguingly, a strong immunological memory effect was obtained by this synergistic therapy. Taking all these results into consideration, we anticipate that the photo-chemo-immunotherapy strategies show great promise toward the development of a multifunctional platform for anticancer therapeutic applications.

Melanin-dot-mediated delivery of metallacycle for NIR-II/photoacoustic dual-modal imaging-guided chemo-photothermal synergistic therapy.

Discrete Pt(II) metallacycles have potential applications in biomedicine. Herein, we engineered a dual-modal imaging and chemo-photothermal therapeutic nano-agent 1 that incorporates discrete Pt(II) metallacycle 2 and fluorescent dye 3 (emission wavelength in the second near-infrared channel [NIR-II]) into multifunctional melanin dots with photoacoustic signal and photothermal features. Nano-agent 1 has a good solubility, biocompatibility, and stability in vivo. Both photoacoustic imaging and NIR-II imaging in vivo confirmed that 1 can effectively accumulate at tumor sites with good signal-to-background ratio and favorable distribution. Guided by precise dual-modal imaging, nano-agent 1 exhibits a superior antitumor performance and less severe side effects compared with a single treatment because of the high efficiency of the chemo-photothermal synergistic therapy. This study shows that nano-agent 1 provides a promising multifunctional theranostic platform for potential applications in biomedicine.