Fourier domain mode-locked opto-electronic oscillator with a diode-tuned bandpass filter.

We report what we believe to be the first Fourier domain mode-locked (FDML) opto-electronic oscillator (OEO) without using a tunable signal source to implement, such as a tunable laser or a tunable microwave source as described in the previous reports. We designed and fabricated a tunable microwave filter with individually packaged microwave components, in which a low cost diode-tuned phase shifter was used to rapidly tune the filter center frequency. We successfully realized Fourier domain mode-locking of an OEO using the diode-tuned filter and obtained linearly chirped microwave signals around 9 GHz with a chirp rate of 36 MHz/µs and a frequency tuning range of 0.4 GHz, which can be extended to 142 MHz/µs and 1.56 GHz, respectively, with a filter circuit using chip sized components. We found, for the first time to the best of authors' knowledge, that the phase noise of FDML OEO's delayed self-heterodyne signal is an excellent indicator for mode-locking frequency optimization, which had a "U" shape dependence on the detuning of the mode-locking frequency with a locking range of over 40 Hz. We also investigated harmonic mode-locking of the FDML up to 5th harmonics and achieved a chirp rate of 180 MHz/µs using the tunable filter of individually packaged components. Compared with the previous FDML OEO's implemented with tunable signal sources, our diode tuned FDML OEO has the advantages of low cost, compact size, excellent frequency tuning linearity, easy implemention and immunity to laser frequency drift and noise for achieving better frequency repeatability and lower phase noise.

Cinnamaldehyde: Pharmacokinetics, anticancer properties and therapeutic potential (Review).

Cancer incidence is increasing globally, presenting a growing public health challenge. While anticancer drugs are crucial in treatment, their limitations, including poor targeting ability and high toxicity, hinder effectiveness and patient safety, requiring relentless scientific research and technological advancements to develop safer and more effective therapeutics. Cinnamaldehyde (CA), an active compound derived from the natural plant cinnamon, has garnered attention in pharmacological research due to its diverse therapeutic applications. CA has potential in treating a wide array of conditions, including cardiovascular diseases, diabetes, inflammatory disorders and various forms of cancer. The present review comprehensively summarizes the physicochemical and pharmacokinetic profiles of CA, and delves into the latest advancements in elucidating its potential mechanisms and targets across various cancer types. CA and its derivatives have antitumor effects, which encompass inhibiting cell proliferation, arresting the cell cycle, inducing apoptosis, limiting cell migration and invasion, and suppressing angiogenesis. Additionally, the present review explores targeted formulations of CA, laying a scientific foundation for further exploration of its implications in cancer prevention and treatment strategies.

Anti-Toxoplasma gondii effect of tylosin in vitro and in vivo.

BACKGROUND: Toxoplasma gondii is an important protozoan pathogen with medical and veterinary importance worldwide. Drugs currently used for treatment of toxoplasmosis are less effective and sometimes cause serious side effects. There is an urgent need for the development of more effective drugs with relatively low toxicity. METHODS: The effect of tylosin on the viability of host cells was measured using CCK8 assays. To assess the inhibition of tylosin on T. gondii proliferation, a real-time PCR targeting the B1 gene was developed for T. gondii detection and quantification. Total RNA was extracted from parasites treated with tylosin and then subjected to transcriptome analysis by RNA sequencing (RNA-seq). Finally, murine infection models of toxoplasmosis were used to evaluate the protective efficacy of tylosin against T. gondii virulent RH strain or avirulent ME49 strain. RESULTS: We found that tylosin displayed low host toxicity, and its 50% inhibitory concentration was 175.3 µM. Tylsoin also inhibited intracellular T. gondii tachyzoite proliferation, with a 50% effective concentration of 9.759 µM. Transcriptome analysis showed that tylosin remarkably perturbed the gene expression of T. gondii, and genes involved in "ribosome biogenesis (GO:0042254)" and "ribosome (GO:0005840)" were significantly dys-regulated. In a murine model, tylosin treatment alone (100 mg/kg, i.p.) or in combination with sulfadiazine sodium (200 mg/kg, i.g.) significantly prolonged the survival time and raised the survival rate of animals infected with T. gondii virulent RH or avirulent ME49 strain. Meanwhile, treatment with tylosin significantly decreased the parasite burdens in multiple organs and decreased the spleen index of mice with acute toxoplasmosis. CONCLUSIONS: Our findings suggest that tylosin exhibited potency against T. gondii both in vitro and in vivo, which offers promise for treatment of human toxoplasmosis.

Gold Nanorods and Polymer Micelles Mediated Dual TLR Stimulators Delivery System CPG@Au NRs/M-R848 Regulate Macrophages Reprogramming and DC Maturation for Enhanced Photothermal Immunotherapy of Melanoma.

Synergistic photothermal immunotherapy has emerged as a favorable therapeutic approach to fight cancer. However, design of an effective photothermal immunotherapy system to suppress tumor growth and simultaneously inhibit tumor metastases continues to be a challenge. Here a dual toll-like receptor agonists delivery system CPG@Au NRs/m-R848 for combined photothermal immunotherapy of melanoma is developed. CPG@Au NRs/m-R848 displays strong antitumor effects by promoting maturation of dendritic cells (DCs) and reprogramming of M2 macrophages into M1 phenotype. Moreover, immunogenic cell death (ICD) induced by photothermal ablation of Au NRs could synergistically produce in situ vaccination effect with CPG ODN and R848, generating systemic and lasting antitumor immunity. It is further proved that CPG@Au NRs/m-R848 treatment inhibits tumor growth in bilateral B16F10 tumors model by eliciting CD8+ T cell response. Overall, this work suggests that this strategy hold great potential in tumor immunotherapy by regulating tumor-associated macrophage polarization, triggering DCs maturation and inducing ICD.

Sustained co-delivery of 5-fluorouracil and cis-platinum via biodegradable thermo-sensitive hydrogel for intraoperative synergistic combination chemotherapy of gastric cancer.

Gastric cancer is the fifth most common cancer and the third leading cause of cancer death worldwide, posing a severe threat to human health. Surgical resection remains the most preferred option for gastric cancer treatment. However, for advanced gastric cancer, the curative effect of surgical resection is usually limited by the local recurrence, peritoneal carcinomatosis, or distal metastasis. Intraoperative chemotherapy is an attractive in situ adjuvant treatment strategy to reduce the recurrence and metastasis after surgical resection. Here, we designed a 5-fluorouracil (5-FU) and cis-platinum (DDP) co-delivery system based on a biodegradable temperature-sensitive hydrogel (PDLLA-PEG-PDLLA, PLEL) for intraoperative adjuvant combination chemotherapy of gastric cancer. This 5-FU + DDP/PLEL hydrogel system characterized by a special sol-gel phase transition in response to physiological temperature and presented sustained drug release in vitro and in vivo. A strong synergistic cell proliferation inhibition and apoptosis promotion of 5-FU + DDP/PLEL were observed against gastric cancer MKN45-luc cells. After intraperitoneal injection, the dual-drug loaded hydrogel formulation showed superior anti-tumor effects than the single-drug carrying hydrogels and combination of free 5-FU and DDP on the gastric cancer peritoneal carcinomatosis model. The use of hydrogel for dual-drug delivery had benefited to fewer side effects as well. What's more, we established a mouse model for postsurgical residual tumors and peritoneal carcinomatosis of gastric cancer, in which the intraoperative administration of 5-FU + DDP/PLEL also remarkably inhibited the local recurrence of the orthotopic tumors and the growth of the abdominal metastatic tumors, resulting in an extended lifetime. Hence, this developed dual-drug loaded hydrogel system has great potential in the intraoperative chemotherapy of gastric cancer, that suggests a clinically-relevant and valuable option for postsurgical management of gastric cancer.

RGD peptide modified platinum nanozyme Co-loaded glutathione-responsive prodrug nanoparticles for enhanced chemo-photodynamic bladder cancer therapy.

Bladder cancer is one of the most common malignant tumors in the urinary system worldwide. The poor permeability and uncontrollable release of drug and hypoxia of tumor tissues were the main reasons leading to poor therapeutic effect of chemo-photodynamic therapy for bladder cancer. To solve the above problems, a tumor-targeting peptide Arg-Gly-Asp (RGD) modified platinum nanozyme (PtNP) co-loaded glutathione (GSH)-responsive prodrug nanoparticles (PTX-SS-HPPH/Pt@RGD-NP) was constructed. Firstly, a GSH-responsive prodrug (PTX-SS-HPPH) was prepared by introducing a disulfide bond between paclitaxel (PTX) and photosensitizer 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH), which could realize the GSH-responsive release of the drug at the tumor sites. Also, the distearoylphosphoethanolamine-poly (ethylene glycol)-RGD peptide (DSPE-PEG-RGD) modified the prodrug to enhance the targeting and permeability ability to bladder cancer cells. Besides, to alleviate the hypoxia of tumor tissues, PtNP was introduced to produce oxygen (O2) and improve photodynamic therapy efficiency. The results showed that the PTX-SS-HPPH/Pt@RGD-NP could achieve GSH-responsive drug release in tumor microenvironment, enhance the drug accumulation time and permeability at tumor sites in T24 subcutaneous tumor model and T24 orthotopic bladder tumor model, and alleviate hypoxia in tumor tissues, thus realizing enhanced chemo-photodynamic therapy for bladder cancer, and providing new strategies and methods for clinical treatment of bladder cancer.

Tumor microenvironment-responsive Ag2S-PAsp(DOX)-cRGD nanoparticles-mediated photochemotherapy enhances the immune response to tumor therapy.

Chemotherapy drugs play important roles in clinical treatment, and most first-line regimens of cancer therapy contain chemotherapy drugs. In particular, some chemotherapeutic drugs can also produce ICD effect and enhance the immune response of the body. However, most chemotherapy drugs do not specifically target tumors or the complex tumor microenvironment, which renders their curative effect insufficient. Therefore, we constructed a tumor microenvironment-responsive drug delivery system (Ag2S-PAsp-cRGD) combined with doxorubicin (DOX) for tumor therapy. Firstly, Ag2S nanoparticles (NPs) were modified with polymer aspartic acid (PAsp) to construct the drug-loading platform. Then, an active targeting ligand (cRGD) was coupled through an amide reaction to enhance the functional targeting ability of the drug delivery system. In vivo imaging of the system showed that the nanoparticles accumulated in the tumor site, which facilitated the delivery of the chemotherapy drug DOX to the targeted tumor site. Furthermore, the photothermal effect of Ag2S NPs can effectively killed tumor cells, and also helped the release of DOX from nanoparticles into tumor tissue, thus enhancing the chemotherapeutic effect. Moreover, combined with the ICD effect jointly induced by photothermal therapy (PTT) and DOX, the treatment further activated the host immune response against tumors by enhancing the presentation of antigens and promoting the differentiation of T cells. This strategy of photo-chemo-immunotherapy showed excellent antitumor effect, not only eliminating the primary tumor but also preventing recurrence and inhibiting metastasis.

Review of a new bone tumor therapy strategy based on bifunctional biomaterials.

Bone tumors, especially those in osteosarcoma, usually occur in adolescents. The standard clinical treatment includes chemotherapy, surgical therapy, and radiation therapy. Unfortunately, surgical resection often fails to completely remove the tumor, which is the main cause of postoperative recurrence and metastasis, resulting in a high mortality rate. Moreover, bone tumors often invade large areas of bone, which cannot repair itself, and causes a serious effect on the quality of life of patients. Thus, bone tumor therapy and bone regeneration are challenging in the clinic. Herein, this review presents the recent developments in bifunctional biomaterials to achieve a new strategy for bone tumor therapy. The selected bifunctional materials include 3D-printed scaffolds, nano/microparticle-containing scaffolds, hydrogels, and bone-targeting nanomaterials. Numerous related studies on bifunctional biomaterials combining tumor photothermal therapy with enhanced bone regeneration were reviewed. Finally, a perspective on the future development of biomaterials for tumor therapy and bone tissue engineering is discussed. This review will provide a useful reference for bone tumor-related disease and the field of complex diseases to combine tumor therapy and tissue engineering.

Curcumin-Microsphere/IR820 Hybrid Bifunctional Hydrogels for In Situ Osteosarcoma Chemo-co-Thermal Therapy and Bone Reconstruction.

Conventional biomaterial-mediated osteosarcoma therapy mainly focuses on its antitumor effect yet often fails to overcome the problem of post-treatment bone tissue defect repair. Simultaneously, minimally invasive drug delivery methods are becoming spotlights for normal tissue preservation. Herein, an injectable curcumin-microsphere/IR820 coloaded hybrid methylcellulose hydrogel (Cur-MP/IR820 gel) platform was designed for osteosarcoma therapy and bone regeneration. In vitro, the K7M2wt osteosarcoma cells were eradicated by hyperthermia and curcumin. Later, the sustained release of curcumin promoted alkaline phosphatase expression and calcium deposition of bone mesenchymal stem cells. In vivo, this hybrid hydrogel could reach tumor site via injection and turned into hydrogel due to heat sensitivity. Under the irradiation of an 808 nm laser, localized hyperthermia (∼51 °C) generated in 5 min to ablate the tumor. Meanwhile, the thermal-accelerated curcumin release and thermal-increased cell membrane permeability led to tumor cell apoptosis. Tumors in photothermal-co-chemotherapy group were successfully restrained from day 2 after treatment. After that, bone reconstruction was promoted because of sustained released curcumin. The chemo-co-thermal efficacy and osteogenic capacity of Cur-MP/IR820 hydrogel suggest a promising approach to the treatment of osteosarcoma and provide provoking inspiration for treating bone tumors and repairing bone tissue.

Upregulation of lncRNA147410.3 in the Brain of Mice With Chronic Toxoplasma Infection Promoted Microglia Apoptosis by Regulating Hoxb3.

Toxoplasma gondii is neurotropic and affects the function of nerve cells, while the mechanism is unclear. LncRNAs are abundantly enriched in the brain and participated in the delicate regulation of the central nervous system (CNS) development. However, whether these lncRNAs are involved in the regulation of microglia activation during the process of T. gondii infection is largely unknown. In this study, the upregulation of a novel lncRNA147410.3 (ENSMUST00000147410.3) was identified as a key factor to influence this process. The target gene of lncRNA147410.3 was predicted and identified as Hoxb3. The localization of lncRNA147410.3 in the brain and cells was proved in the nucleus of neuroglia through FISH assay. Furthermore, the function of lncRNA147410.3 on neuronal cell was confirmed that lncRNA147410.3 could affect proliferation, differentiation, and apoptosis of mouse microglia by positively regulating Hoxb3. Thus, our study explored the modulatory action of lncRNA147410.3 in T. gondii infected mouse brain, providing a scientific basis for using lncRNA147410.3 as a therapeutic target to treat neurological disorder induced by T. gondii.

Intracellular aggregation of peptide-reprogrammed small molecule nanoassemblies enhances cancer chemotherapy and combinatorial immunotherapy.

The intracellular retention of nanotherapeutics is essential for their therapeutic activity. The immobilization of nanotherapeutics inside target cell types can regulate various cell behaviors. However, strategies for the intracellular immobilization of nanoparticles are limited. Herein, a cisplatin prodrug was synthesized and utilized as a glutathione (GSH)-activated linker to induce aggregation of the cisplatin prodrug/IR820/docetaxel nanoassembly. The nanoassembly has been reprogrammed with peptide-containing moieties for tumor-targeting and PD-1/PD-L1 blockade. The aggregation of the nanoassemblies is dependent on GSH concentration. Evaluations in vitro and in vivo revealed that GSH-induced intracellular aggregation of the nanoassemblies enhances therapeutic activity in primary tumors by enhancing the accumulation and prolonging the retention of the chemotherapeutics in the tumor site and inducing reactive oxygen species (ROS) generation and immunogenic cell death. Moreover, the nanoassemblies reinvigorate the immunocytes, especially the systemic immunocytes, and thereby alleviate pulmonary metastasis, even though the population of immunocytes in the primary tumor site is suppressed due to the enhanced accumulation of chemotherapeutics. This strategy provides a promising option for the intracellular immobilization of nanoparticles in vitro and in vivo.

Effects of Docetaxel Injection and Docetaxel Micelles on the Intestinal Barrier and Intestinal Microbiota.

Increasing evidence has suggested that chemotherapeutics affect the integrity of the intestinal barrier and alter the intestinal microbiota, thus limiting the therapeutic outcomes of cancer chemotherapy. Docetaxel (DTX) is used for breast cancer treatment and has gastrointestinal side effects, but the influence of DTX formulations on the intestinal barrier and intestinal microbiota remains unknown. Therefore, in this work, the influence of DTX injection (free DTX, commercial formulation) and DTX/methoxy poly(ethylene glycol)-block-poly(D,L-lactide) (mPEG-PDLLA) (DTX micelles, nanoformulation) on the integrity of the intestinal barrier and the intestinal microbiota is investigated. It is found that the free DTX causes significantly greater intestinal barrier damage than the DTX micelles. The diversity of the intestinal microbiota, and the relative abundance of Akkermansia muciniphila and Ruminococcus gnavus in the DTX micelle-treated group is significantly higher than that in the free DTX-treated group. Moreover, the tumor growth rate is elevated in antibiotic mixture-pretreated mice, demonstrating that the diversity and composition of the intestinal microbiota may be associated with tumor progression. This work demonstrates that different formulations of chemotherapeutics have different effects on the integrity of the intestinal barrier and the intestinal microbiota.

Erratum to "Near-infrared responsive 5-fluorouracil and indocyanine green loaded MPEG-PCL nanoparticle integrated with dissolvable microneedle for skin cancer therapy" [Bioact. Mater. 5 (2020) 542-552].

[This corrects the article DOI: 10.1016/j.bioactmat.2020.04.002.].

Ag2S nanoparticle-mediated multiple ablations reinvigorates the immune response for enhanced cancer photo-immunotherapy.

Photothermal therapy (PTT) has been widely used in cancer treatment in recent years. However, it is difficult to completely eliminate tumors by single PTT, and the effects of single dose of PTT frequency on the therapeutic outcome of PTT and the multiple PTT-induced immune response in cancer therapy also remain unclear. Here, water-soluble Ag2S nanoparticles (NPs) with optimal particle size (~15 nm) were synthesized and used as the PTT agents. The in vitro and in vivo results demonstrated that Ag2S NPs had good photothermal conversion in response to the irradiation of an 808 nm laser, and the results indicated that the NPs have potential as contrast agents for photoacoustic imaging as well as good biocompatibility. The in vivo results further revealed that the frequency of the Ag2S NP-mediated PTT affected the cancer therapeutic outcome. The increase of frequency efficiently reduced the primary tumor recurrence and alleviated metastasis. The present study suggested that the mechanism involves multiple PTT cycles inhibiting the proliferation of primary tumor cells and stimulating the systematic immune response in the mouse breast cancer model. Therefore, frequency optimization in photothermal ablation may provide a promising strategy to enhance the therapeutic outcome in cancer therapy.

Rapid Electrochemical Screening of Phenylketonuria Maker Depending on Dehydrogenase Attached to the Pt-Doped Reduced Graphene Oxide Nanocomposites.

Phenylketonuria (PKU) is a common disease associated with amino acid metabolism, and usually occurs in newborns. It can cause serious neurological diseases and even death. However, owing to inadequate-effective treatment, it can only be slowed by a low-phenylalanine (Phe) diet. In addition, PKU screening is essential for newborns in many countries. Therefore, rapid screening is crucial for preventing damage and meeting the large sample diagnosis demand. For confirmed patients, a convenient method to monitor their regular Phe levels is required. However, current clinical methods do not meet the rapid screening and convenient monitoring requirements. Herein, a rapid and facile electrochemical device based on platinum-doped reduced graphene oxide nanocomposites was developed to detect PKU biomarker-Phe. The results demonstrated that the developed electrode has great sensitivity, selectivity, and stability. The detection range was 0.0001 mM to 6 mM with a limit of detection of 0.01 µM. Therefore, this work offers a simple and rapid method for point-of-care PKU screening and daily monitoring.

A Nonenzymatic Hydrogen Peroxide Electrochemical Sensing and Application in Cancer Diagnosis.

The diagnosis of malignant tumors is essential for informing clinical decisions regarding therapeutic options. Current imaging and pathological diagnostic methods do not provide quantitative molecular information that is important in tumor identification. Moreover, pathological tissue analysis is dependent on unevenly distributed pathological features. The tumor microenvironment has been documented to have hydrogen peroxide (H2 O2 ). This study presents a biologically sensitive and efficient H2 O2 electrochemical sensor based on PtNi nanoparticle-doped N-reduced graphene oxide (PtNi-N-rGO) with a low detection limit (2.8 × 10-9 m), a fast response time (<6 s) and desirable anti-interference characteristics. Herein, H2 O2 is used as molecular biomarker. The sensor successfully captures H2 O2 from cancer cells. In addition, it efficiently detects tumor tissues, adjacent tissues, and normal tissues. This study demonstrates the H2 O2 sensor potential to rapidly detect tumor tissues. This technique provides a complementary method for pathological tumor diagnosis that is independent of the traditional pathology labs.

Polymeric Nanoparticles with ROS-Responsive Prodrug and Platinum Nanozyme for Enhanced Chemophotodynamic Therapy of Colon Cancer.

The combination of chemotherapy and photodynamic therapy (PDT) has promising potential in the synergistic treatment of cancer. However, chemotherapy and photodynamic synergistic therapy are impeded by uncontrolled chemotherapeutics release behavior, targeting deficiencies, and hypoxia-associated poor PDT efficacy in solid tumors. Here, a platinum nanozyme (PtNP) loaded reactive oxygen species (ROS)-responsive prodrug nanoparticle (CPT-TK-HPPH/Pt NP) is created to overcome these limitations. The ROS-responsive prodrug consists of a thioketal bond linked with camptothecin (CPT) and photosensitizer-2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH). The PtNP in CPT-TK-HPPH/Pt NP can efficiently catalyze the decomposition of hydrogen peroxide (H2O2) into oxygen to relieve hypoxia. The production of oxygen can satisfy the consumption of HPPH under 660 nm laser irradiation to attain the on-demand release of CPT and ensure enhanced photodynamic therapy. As a tumor diagnosis agent, the results of photoacoustic imaging and fluorescence imaging for CPT-TK-HPPH/Pt NP exhibit desirable long circulation and enhanced in vivo targeting. CPT-TK-HPPH/Pt NPs effectively inhibit tumor proliferation and growth in vitro and in vivo. CPT-TK-HPPH/Pt NP, with its excellent ROS-responsive drug release behavior and enhanced PDT efficiency can serve as a new cancer theranostic agent, and will further promote the research of chemophotodynamic synergistic cancer therapy.

Near-infrared responsive 5-fluorouracil and indocyanine green loaded MPEG-PCL nanoparticle integrated with dissolvable microneedle for skin cancer therapy.

The prevalence of skin cancer is rising along with the rapid population aging in recent years. Traditional therapies, such as surgical treatment, radiotherapy, chemotherapy, photodynamic therapy, and immunotherapy, may accompany serious side effects, limiting their clinical benefits. According to the biological characteristics of skin cancer, we have already established two kinds of synergetic systems of photothermal therapy (microneedle) and chemotherapy, containing gold nanorods (GNR). Although the microneedle system exhibited great potential for skin cancer treatment, the system could be still improved further. So, we designed a near-infrared light-responsive 5-fluorouracil (5-Fu) and indocyanine green (ICG) loaded monomethoxy-poly (ethylene glycol)-polycaprolactone (MPEG-PCL) nanoparticle (5-Fu-ICG-MPEG-PCL), and then 5-Fu-ICG-MPEG-PCL was integrated with a hyaluronic acid dissolvable microneedle system (HA MN) to get 5-Fu-ICG-MPEG-PCL loaded HA MN for treating skin cancers, including human epidermoid cancer and melanoma. In this system, hyaluronic acid, the microneedle carrier, possesses good skin penetration ability and is approved by FDA as a pharmaceutical adjuvant; 5-Fu is recommended by FDA for skin cancer treatment; ICG, a photothermal agent, possesses a strong photothermal ability and is approved by FDA for its use in the human body. We hypothesized that 5-Fu-ICG-MPEG-PCL could be delivered by the dissolvable microneedle through the skin, and the release behavior of the drug in the nanoparticle could be controlled by near-infrared light for achieving a single-dose cure of skin cancer, improving the cure rate of skin cancer and providing a new idea and possibility for the clinical treatment of skin cancer.

Ultrasmall CuS@BSA nanoparticles with mild photothermal conversion synergistically induce MSCs-differentiated fibroblast and improve skin regeneration.

Mesenchymal stem cell (MSC)-based therapies have been used in skin regeneration due to their ability to differentiate into many cells, promote cytokine secretion and participate in collagen deposition. In this study, we concluded that a CuS@BSA nanoparticles exhibited similar potential in inducing MSCs differentiation to fibroblasts as Cu ions for wound healing. Methods: First, we verified the photothermal efficiency of CuS@BSA in vivo and vitro and had no cytotoxicity for MSCs when the temperature was controlled at 42 °C by adjusting the power of irradiation at 980 nm. And then we detected the expression of vimentin in MSCs, which further directed the MSCs to fibroblasts through Western blotting and Immunofluorescence when treated with CuS@BSA or pre-heat at 42 °C. In addition, we implanted MSCs into the Matrigel or electrospun PLA nanofiber membrane in vitro to evaluating the effect of heating or CuS@BSA on the morphological change of MSCs by SEM. Finally, we evaluated improving skin regeneration by the combination of preheated-MSCs and CuS@BSA nanoparticles that were encapsulated in Matrigel. Results: The CuS@BSA nanoparticles have good photothermal conversion efficiency. Not only CuS nanoparticles itself or after irradiation at 980 nm stimulated the expressioin of vimentin in MSCs. Besides, the CuS@BSA can promote cell proliferation as Cu ion through the expression of ERK. The combination of the CuS@BSA nanoparticles and thermal treatment synergistically improved the closure of an injured wound in an injured wound model. Conclusions: MSCs combined with CuS@BSA are a promising wound dressing for the reconstruction of full-thickness skin injuries.

Rationally designed peptide-conjugated gold/platinum nanosystem with active tumor-targeting for enhancing tumor photothermal-immunotherapy.

Because of the tumor heterogeneity, poor therapeutic outcome is obtained while the conventional treatments, such as surgery, radiotherapy, or chemotherapy are utilized alone. Herein, combinational therapy strategies have been introduced to solve this problem. Photothermal therapy (PTT) as a non-invasive thermal therapeutic manner has attracting enormous attentions not only for the effective inhibition in primary tumors, but also for producing tumor-associated antigens from ablated tumor cell residues which exhibit the feasibility to enhance the therapeutic outcome of immunotherapy. Here, we report the construction and application of Au@Pt-based nanosystem with rationally designed peptide (LyP-1-PLGVRG-DPPA-1, LMDP) conjugation for cancer photothermal-immunotherapy. The obtained Au@Pt-LMDP nanosystem can serve as a matrix metalloproteinase (MMP) activated tumor targeting agents for effective photothermal therapy together with immune checkpoint blockade immunotherapy by the on-demand release of a D-peptide antagonist of programmed cell death-ligand 1 (PD-L1). The PA imaging demonstrates its effective accumulation in the tumor region by the activated tumor targeting moiety derived from the LMDP. Moreover, in vivo anti-tumor studies reveal that Au@Pt-LMDP nanosystem can effectively eliminate primary tumors via PTT, and further stimulate the activation of cytotoxic T lymphocytes by PD-L1 immune checkpoint blockage, result in inhibiting the growth of distal tumors and alleviating tumor metastasis. The present study provides a promising strategy for the combination treatment of advanced cancer and obtains a valuable therapeutic outcome in tumor photothermal-immunotherapy.