Hippophae Rhamnoides-derived Phytomedicine Nano-System Modulates Bax/Fas Pathways to Reduce Proliferation in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most common primary tumor of the breast with limited effectual drug availability. Therefore, the aim of the study is to develop an innovative phyto-nanomedicine (PNM) to cure TNBC with the least genotoxicity. Hereinafter, the sea buckthorn' extracted polyphenols (SBP), combine with metformin (MET), are synthesized as a novel PNM to evaluate its anti-tumor properties, effectiveness, and mechanism of action in TNBC in vitro and in vivo models. The SBP exhibits 16 new kinds of polyphenols that are been reported earlier which regulated cell development, proliferation, and programmed cell death (PCD) effectively. SBP-MET PNM inhibits MDA-MB-231 (47%), MDA-MB-436 (46%), and 4T1 (46%) cell proliferation but does not affect L929 normal murine cell development and successfully induce PCD (73.19%) in MDA-MB-231 cells. Mechanistically, in vivo SBP-MET proteome expression profiling reveals upregulation of proapoptotic Bax protein and activation of Fas signaling pathways convince downstream Daxx and FADD proteins, which further triggers Caspase-3 that prompts apoptosis in human TNBC cells by cleaving PARP-1 protein. Current findings establish innovative highly biocompatible phyto-nanomedicine that has significant potential to inhibit TNBC cell growth and induce regulated cell death (RCD) in vivo model, thereby opening a new arena for TNBC therapy.

Nitroxide radical conjugated ovalbumin theranostic nanosystem for enhanced dendritic cell-based immunotherapy and T1-magnetic resonance imaging.

Melanoma, known for its aggressive metastatic nature, presents a formidable challenge in cancer treatment, where conventional therapies often fall short. This study introduces a pioneering approach utilizing metal-free nanosystem as tumor vaccines, spotlighting their potential in revolutionizing melanoma treatment. This work employed organic nitroxides, specifically 4-carboxy-TEMPO, in combination with chitosan (CS), to create a novel nanocomposite material - the CS-TEMPO-OVA nanovaccines. This composition not only improves biocompatibility and extends blood circulation time of TEMPO but also marks a significant departure from traditional gadolinium-based contrast agents in MRI technology, addressing safety concerns. CS-TEMPO-OVA nanovaccines demonstrate excellent biocompatibility at both the cellular and organoid level. They effectively stimulate bone marrow-derived dendritic cells (BMDCs), which in turn promote the maturation and activation of T cells. This ultimately leads to a strong production of essential cytokines. These nanovaccines serve a dual purpose as both therapeutic and preventive. By inducing an immune response, activating cytotoxic T cells, and promoting macrophage M1 polarization, they effectively inhibit melanoma growth and enhance survival in mouse models. When combined with αPD-1, the CS-TEMPO-OVA nanovaccines significantly bolster the infiltration of cytotoxic T lymphocytes (CTLs) within tumors, sparking a powerful systemic antitumor response that effectively curbs tumor metastasis. The ability of these nanovaccines to control both primary (subcutaneous) and metastatic B16-OVA tumors highlights their remarkable efficacy. Furthermore, the CS-TEMPO-OVA nanovaccine can be administered in vivo via both intravenous and intramuscular routes, both of which effectively enhance the T1 contrast of magnetic resonance imaging in tumor tissue. This study offers invaluable insights into the integrated application of these nanovaccines in both clinical diagnostics and treatment, marking a significant stride in cancer research and patient care.

Near-infrared-II responsive ovalbumin functionalized gold-genipin nanosystem cascading photo-immunotherapy of cancer.

Synergistic cancer therapies have attracted wide attention owing to their multi-mode tumor inhibition properties. Especially, photo-responsive photoimmunotherapy demonstrates an emerging cancer treatment paradigm that significantly improved treatment efficiency. Herein, near-infrared-II responsive ovalbumin functionalized Gold-Genipin nanosystem (Au-G-OVA NRs) was designed for immunotherapy and deep photothermal therapy of breast cancer. A facile synthesis method was employed to prepare the homogeneous Au nanorods (Au NRs) with good dispersion. The nanovaccine was developed further by the chemical cross-linking of Au-NRs, genipin and ovalbumin. The Au-G-OVA NRs outstanding aqueous solubility, and biocompatibility against normal and cancer cells. The designed NRs possessed enhanced localized surface plasmon resonance (LSPR) effect, which extended the NIR absorption in the second window, enabling promising photothermal properties. Moreover, genipin coating provided complimentary red fluorescent and prepared Au-G-OVA NRs showed significant intracellular encapsulation for efficient photoimmunotherapy outcomes. The designed nanosystem possessed deep photothermal therapy of breast cancer and 90% 4T1 cells were ablated by Au-G-OVA NRs (80µg ml-1concentration) after 1064 nm laser irradiation. In addition, Au-G-OVA NRs demonstrated outstanding vaccination phenomena by facilitating OVA delivery, antigen uptake, maturation of bone marrow dendritic cells, and cytokine IFN-γsecretion for tumor immunosurveillance. The aforementioned advantages permit the utilization of fluorescence imaging-guided photo-immunotherapy for cancers, demonstrating a straightforward approach for developing nanovaccines tailored to precise tumor treatment.

Engineering Titanium-Hydroxyapatite Nanocomposite Hydrogels for Enhanced Antibacterial and Wound Healing Efficacy.

External factors often lead to predictable damage, such as chemical injuries, burns, incisions, and wounds. Bacterial resistance to antibiotics at wound sites underscores the importance of developing hydrogel composite systems with inorganic nanoparticles possessing antibacterial properties to treat infected wounds and expedite the skin regeneration process. In this study, a promising TiO2-HAp@PF-127@CBM inorganic and organic integrated hydrogel system was designed to address challenges associated with bacterial resistance and wound healing. The synthesized TiO2-hydroxyapatite (HAp) nanocomposites were coated with an FDA-approved PluronicF-127 polymer and combined with a carbomer hydrogel (CBM) to accomplish the final product. The synthesized nanoparticles exhibit enhanced biocompatibility against L929 and HUVECs and cell proliferation effects. To mitigate oxidative stress caused by TiO2-induced reactive oxygen species in dark environments for effective antibacterial effects, HAp promotes cell proliferation, expediting wound skin layer formation. CBM binds to inorganic nanoparticles, facilitating their gradual release and promoting wound healing. The reduced inflammation and enhanced tissue regeneration observed in the TiO2-HAp@PF-127@CBM group suggest a favorable environment for wound repair. These results align with prior findings highlighting the biocompatibility and wound-healing properties of titanium-HAp-based materials. The ability of the TiO2-HAp@PF-127@CBM hydrogel dressing to promote granulation tissue formation and facilitate epidermal regeneration underscores its potential for promoting antibacterial effects and wound healing applications.

Spike structure of gold nanobranches induces hepatotoxicity in mouse hepatocyte organoid models.

BACKGROUND: Gold nanoparticles (GNPs) have been extensively recognized as an active candidate for a large variety of biomedical applications. However, the clinical conversion of specific types of GNPs has been hindered due to their potential liver toxicity. The origin of their hepatotoxicity and the underlying key factors are still ambiguous. Because the size, shape, and surfactant of GNPs all affect their properties and cytotoxicity. An effective and sensitive platform that can provide deep insights into the cause of GNPs' hepatotoxicity in vitro is therefore highly desired. METHODS: Here, hepatocyte organoid models (Hep-orgs) were constructed to evaluate the shape-dependent hepatotoxicity of GNPs. Two types of GNPs with different nanomorphology, gold nanospheres (GNSs) and spiny gold nanobranches (GNBs), were synthesized as the representative samples. Their shape-dependent effects on mice Hep-orgs' morphology, cellular cytoskeletal structure, mitochondrial structure, oxidative stress, and metabolism were carefully investigated. RESULTS: The results showed that GNBs with higher spikiness and tip curvature exhibited more significant cytotoxicity compared to the rounded GNSs. The spike structure of GNBs leads to a mitochondrial damage, oxidative stress, and metabolic disorder in Hep-orgs. Meanwhile, similar trends can be observed in HepG2 cells and mice models, demonstrating the reliability of the Hep-orgs. CONCLUSIONS: Hep-orgs can serve as an effective platform for exploring the interactions between GNPs and liver cells in a 3D perspective, filling the gap between 2D cell models and animal models. This work further revealed that organoids can be used as an indispensable tool to rapidly screen and explore the toxic mechanism of nanomaterials before considering their biomedical functionalities.

Facile synthesis of manganese-hafnium nanocomposites for multimodal MRI/CT imaging and in vitro photodynamic therapy of colon cancer.

Precise diagnosis of complex and soft tumors is challenging, which limits appropriate treatment options to achieve desired therapeutic outcomes. However, multifunctional nano-sized contrast enhancement agents based on nanoparticles improve the diagnosis accuracy of various diseases such as cancer. Herein, a facile manganese-hafnium nanocomposites (Mn3O4-HfO2 NCs) system was designed for bimodal magnetic resonance imaging (MRI)/computed tomography (CT) contrast enhancement with a complimentary function of photodynamic therapy. The solvothermal method was used to fabricate NCs, and the average size of Mn3O4 NPs and Mn3O4-HfO2 NCs was about 7 nm and 15 nm, respectively, as estimated by TEM. Dynamic light scattering results showed good dispersion and high negative (-33 eV) zeta potential, indicating excellent stability in an aqueous medium. Mn3O4-HfO2 NCs revealed negligible toxic effects on the NCTC clone 929 (L929) and mouse colon cancer cell line (CT26), demonstrating promising biocompatibility. The synthesized Mn3O4-HfO2 NCs exhibit significant enhancement in T1-weighted magnetic resonance imaging (MRI) and X-ray computed tomography (CT), indicating the appropriateness for dual-modal MRI/CT molecular imaging probes. Moreover, ultra-small Mn3O4-HfO2 NCs show good relaxivities for MRI/CT. These nanoprobes Mn3O4-HfO2 NCs further possessed outstanding reactive oxygen species (ROS) generation ability under minute ultraviolet light (6 mW·cm-2) to ablate the colon cancer cells in vitro. Therefore, the designed multifunctional Mn3O4-HfO2 NCs were ideal candidates for cancer diagnosis and photodynamic therapy.

Dumbbell-shaped bimetallic AuPd nanoenzymes for NIR-II cascade catalysis-photothermal synergistic therapy.

The noble metal NPs that are currently applied to photothermal therapy (PTT) have their photoexcitation location mainly in the NIR-I range, and the low tissue penetration limits their therapeutic effect. The complexity of the tumor microenvironment (TME) makes it difficult to inhibit tumor growth completely with a single therapy. Although TME has a high level of H2O2, the intratumor H2O2 content is still insufficient to catalyze the generation of sufficient hydroxide radicals (‧OH) to achieve satisfactory therapeutic effects. The AuPd-GOx-HA (APGH) was obtained from AuPd bimetallic nanodumbbells modified by glucose oxidase (GOx) and hyaluronic acid (HA) for photothermal enhancement of tumor starvation and cascade catalytic therapy in the NIR-II region. The CAT-like activity of AuPd alleviates tumor hypoxia by catalyzing the decomposition of H2O2 into O2. The GOx-mediated intratumoral glucose oxidation on the one hand can block the supply of energy and nutrients essential for tumor growth, leading to tumor starvation. On the other hand, the generated H2O2 can continuously supply local O2, which also exacerbates glucose depletion. The peroxidase-like activity of bimetallic AuPd can catalyze the production of toxic ‧OH radicals from H2O2, enabling cascade catalytic therapy. In addition, the high photothermal conversion efficiency (η = 50.7 %) of APGH nanosystems offers the possibility of photothermal imaging-guided photothermal therapy. The results of cell and animal experiments verified that APGH has good biosafety, tumor targeting, and anticancer effects, and is a precious metal nanotherapeutic system integrating glucose starvation therapy, nano enzyme cascade catalytic therapy, and PTT therapy. This study provides a strategy for photothermal-cascade catalytic synergistic therapy combining both exogenous and endogenous processes. STATEMENT OF SIGNIFICANCE: AuPd-GOx-HA cascade nanoenzymes were prepared as a potent cascade catalytic therapeutic agent, which enhanced glucose depletion, exacerbated tumor starvation and promoted cancer cell apoptosis by increasing ROS production through APGH-like POD activity. The designed system has promising photothermal conversion ability in the NIR-II region, simultaneously realizing photothermal-enhanced catalysis, PTT, and catalysis/PTT synergistic therapy both in vitro and in vivo. The present work provides an approach for designing and developing catalytic-photothermal therapies based on bimetallic nanoenzymatic cascades.

Microfluidic fabrication of X-ray-visible sodium hyaluronate microspheres for embolization.

Catheter embolization is a minimally invasive technique that relies on embolic agents and is now widely used to treat various high-prevalence medical diseases. Embolic agents usually need to be combined with exogenous contrasts to visualize the embolotherapy process. However, the exogenous contrasts are quite simply washed away by blood flow, making it impossible to monitor the embolized location. To solve this problem, a series of sodium hyaluronate (SH) loaded with bismuth sulfide (Bi2S3) nanorods (NRs) microspheres (Bi2S3@SH) were prepared in this study by using 1,4-butaneglycol diglycidyl ether (BDDE) as a crosslinker through single-step microfluidics. Bi2S3@SH-1 microspheres showed the best performance among other prepared microspheres. The fabricated microspheres had uniform size and good dispersibility. Furthermore, the introduction of Bi2S3 NRs synthesized by a hydrothermal method as Computed Tomography (CT) contrast agents improved the mechanical properties of Bi2S3@SH-1 microspheres and endowed the microspheres with excellent X-ray impermeability. The blood compatibility and cytotoxicity test showed that the Bi2S3@SH-1 microspheres had good biocompatibility. In particular, the in vitro simulated embolization experiment results indicate that the Bi2S3@SH-1 microspheres had excellent embolization effect, especially for the small-sized blood vessels of 500-300 and 300 µm. The results showed the prepared Bi2S3@SH-1 microspheres have good biocompatibility and mechanical properties, as well as certain X-ray visibility and excellent embolization effects. We believe that the design and combination of this material has good guiding significance in the field of embolotherapy.

Advanced biomaterials for human glioblastoma multiforme (GBM) drug delivery.

Glioblastoma multiforme (GBM) has several distinctive characteristics linked to a poor early-stage prognosis. The crucial obstacle in the treatment of GBM is the inability of chemo drugs or other anticancer medicines to reach brain tumors due to the blood-brain tumor barrier (BBTB), leading to weak cytotoxic activity and drug resistance. Additionally, there is a limited number of clinically approved anticancer medicines for GBM because of the heterogeneity of this type of tumor. Presently, four FDA-approved drugs are available for the treatment of GBM, i.e., temozolomide, lomustine, carmustine, and bevacizumab. These drugs are primarily used to treat recurrent high-grade gliomas and their symptoms. Unfortunately, despite efforts to treat GBM over the last 60 years, no significant progress has been made in extending the overall survival (OS) of patients with this disease. Therefore, possible treatments and accessible drugs must be modified or advanced medicines developed to treat GBM. Several innovative strategies have been used to overcome these challenges, such as combining traditional therapies with emerging nanoscale-based biomaterials for multifunctional characteristics. These modified nanoscale biomaterials can cross the blood-brain barrier (BBB) and increase chemo-drug sensitivity through improved accumulation and efficiency. Herein, we review the recent developments in organic and inorganic biomaterial-based nanoparticles for GBM drug delivery. Firstly, we present a brief overview of the FDA-approved drugs and some additional chemo drugs for treating GBM, followed by a discussion on the drawbacks of the delivery of these drugs in GBM. Further, the current challenges in the field of GBM drug delivery, significant advancements in biomaterials research to overcome these obstacles, and subsequent considerations and opportunities for the application of biomaterials in the clinical treatment of GBM are highlighted.

DOX-loaded hydroxyapatite nanoclusters for colorectal cancer (CRC) chemotherapy: Evaluation based on the cancer cells and organoids.

It is meaningful to find suitable in vitro models for preclinical toxicology and efficacy evaluation of nanodrugs and nanocarriers or drug screening and promoting clinical transformation of nanocarriers. The emergence and development of organoids technology provide a great possibility to achieve this goal. Herein, we constructed an in vitro 3D organoid model to study the inhibitory effect of nanocarriers on colorectal cancer. And designed hydroxyapatite nanoclusters (c-HAP) mediated by polydopamine (PDA) formed under alkaline conditions (pH 9.0), then used c-HAP to load DOX (c-HAP/DOX) as nanocarrier for improved chemotherapy. In vitro, drug release experiments show that c-HAP/DOX has suitable responsive to pH, can be triggered to the facile release of DOX in a slightly acidic environment (pH 6.0), and maintain specific stability in a neutral pH value (7.4) environment. c-HAP/DOX showed an excellent antitumor effect in the two-dimensional (2D) cell model and three-dimensional (3D) patient-derived colon cancer organoids (PDCCOs) model. In addition, c-HAP/DOX can release a sufficient amount of DOX to produce cytotoxicity in a slightly acidic environment, entering efficiently into the colorectal cancer cells caused endocytosis and induced apoptosis. Therefore, organoids can serve as an effective in vitro model to present the structure and function of colorectal cancer tissues and be used to evaluate the efficacy of nanocarriers for tumors.

Nanomaterial-assisted CRISPR gene-engineering - A hallmark for triple-negative breast cancer therapeutics advancement.

Triple-negative breast cancer (TNBC) is the most violent class of tumor and accounts for 20-24% of total breast carcinoma, in which frequently rare mutation occurs in high frequency. The poor prognosis, recurrence, and metastasis in the brain, heart, liver and lungs decline the lifespan of patients by about 21 months, emphasizing the need for advanced treatment. Recently, the adaptive immunity mechanism of archaea and bacteria, called clustered regularly interspaced short palindromic repeats (CRISPR) combined with nanotechnology, has been utilized as a potent gene manipulating tool with an extensive clinical application in cancer genomics due to its easeful usage and cost-effectiveness. However, CRISPR/Cas are arguably the efficient technology that can be made efficient via organic material-assisted approaches. Despite the efficacy of the CRISPR/Cas@nano complex, problems regarding successful delivery, biodegradability, and toxicity remain to render its medical implications. Therefore, this review is different in focus from past reviews by (i) detailing all possible genetic mechanisms of TNBC occurrence; (ii) available treatments and gene therapies for TNBC; (iii) overview of the delivery system and utilization of CRISPR-nano complex in TNBC, and (iv) recent advances and related toxicity of CRISPR-nano complex towards clinical trials for TNBC.

pH-Responsive Au@Pd bimetallic core-shell nanorods for enhanced synergistic targeted photothermal-augmented nanocatalytic therapy in the second near-infrared window.

Nanotheranostic agents based on plasmonic nanostructures with their resonance wavelengths located in the second near-infrared window (NIR-II) have gained significant attention in profound tumor photothermal therapy. However, the modulation of localized surface plasmon resonance of gold nanomaterials from the first near-infrared (NIR-I) window to the NIR-II window is still challenging. The structures and compositions of the plasmonic nanomaterials have demonstrated promising characteristics in controlling the optical properties of plasmonic nanostructures. Here, gold nanorod (Au NR) coated with an ultrathin palladium (Pd) shell was developed for tumor-targeted NIR-II photothermal-augmented nanocatalytic therapy through the combination of compositional manipulation and structural evolution strategies. These Au@Pd core-shell hybrid NRs (HNRs) were functionalized with biocompatible chitosan (CS) to acquire lower toxicity and higher stability in physiological systems. Further, Au@Pd-CS HNRs were endowed with an excellent targeting ability by conjugating with folic acid (FA). The as-synthesized Au@Pd-CS-FA HNRs show efficient and complete photothermal ablation of tumor cells upon 1064 nm laser irradiation. The remarkable photothermal conversion efficiency of 69.0% was achieved, which is superior to many reported photothermal agents activated in the NIR-II region. Excitingly, Au@Pd-CS-FA HNRs have peroxidase and catalase activities, simultaneously producing ˙OH for catalytic therapy and O2 for relieving tumor hypoxia and photodynamic therapy. Additionally, in vivo tumor photothermal therapy was carried out, where the biocompatible Au@Pd-CS-FA HNRs penetrate intensely into the tumor cells and consequently show remarkable therapeutic effects. The idea about plasmonic modulation behind the bimetallic core-shell nanostructure in this report can be extended to construct new classes of metal-based nanotheranostic agents with dual-modal combined therapy as an alternative to traditional chemotherapy.

Antiviral effects of coinage metal-based nanomaterials to combat COVID-19 and its variants.

The world has been suffering from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, and millions of people have been infected through human-to-human transmission and lost their lives within months. Although multidisciplinary scientific approaches have been employed to fight against this deadly pandemic, various mutations and diverse environments keep producing constraints in treating SARS-CoV-2. Indeed, the efficacy of the developed vaccines has been limited, and inoculation with the vaccines does not guarantee complete protection even though multiple doses are required, which is a frustrating process. Historically, coinage metals (Cu, Ag, and Au) have been well-known for their effectiveness in antiviral action as well as good biocompatibility, binding receptor inhibition, reactive oxygen species, and phototherapy properties. Thus, this review highlights the diagnostic and therapeutic mechanisms of SARS-CoV-2 using the antivirus ability and mode of action of coinage metals such as viral entry mechanisms into host cells and the NP-inhibition process, which are explained in detail. This article also draws attention to coinage metal nanomaterial-based approaches to treat other contagious viruses. In addition, coinage metal-based biosensors and an overview of some other biocompatible metal-based nanomaterials to fight against SARS-CoV-2 variants are discussed. Finally, the advantages, perspectives and challenges of coinage metal nanoparticles are given to fight against viral infections in the future.

A biomineralized Prussian blue nanotherapeutic for enhanced cancer photothermal therapy.

Photothermal therapy is a promising tumor ablation technique that converts light into heat energy to kill cancer cells. Prussian blue (PB), a biocompatible photothermal reagent, has been widely explored for cancer treatment. However, the translational potential of PB is severely hampered by its low photothermal conversion efficiency (PCE) and poor stability. To tackle these issues, we adopted the biomineralization modality where PB was integrated with calcium phosphate (CaP) through the binding between calcium ions and PB. The mineralized PB (CaP&PB) demonstrated significantly improved PCE (40.2%), resulting from a calcium-induced bandgap-narrowing effect, and exhibited superior suspension stability. Using a 4T1 orthotopic breast cancer BALB/c mouse model, we observed that mineralized PB showed a significant temperature increase within the tumor, which led to better tumoricidal activity compared with CaP and PB when identical NIR treatment was applied. These achievements demonstrated the success of introducing calcium phosphate into Prussian blue by biomineralization to improve the PCE and stability of photothermal reagents, suggesting an alternative translational strategy for enhanced cancer photothermal therapy.

Chemotherapeutic nanomaterials in tumor boundary delineation: Prospects for effective tumor treatment.

Accurately delineating tumor boundaries is key to predicting survival rates of cancer patients and assessing response of tumor microenvironment to various therapeutic techniques such as chemotherapy and radiotherapy. This review discusses various strategies that have been deployed to accurately delineate tumor boundaries with particular emphasis on the potential of chemotherapeutic nanomaterials in tumor boundary delineation. It also compiles the types of tumors that have been successfully delineated by currently available strategies. Finally, the challenges that still abound in accurate tumor boundary delineation are presented alongside possible perspective strategies to either ameliorate or solve the problems. It is expected that the information communicated herein will form the first compendious baseline information on tumor boundary delineation with chemotherapeutic nanomaterials and provide useful insights into future possible paths to advancing current available tumor boundary delineation approaches to achieve efficacious tumor therapy.

Manganese Phosphate-Doxorubicin-Based Nanomedicines Using Mimetic Mineralization for Cancer Chemotherapy.

Inorganic nanomaterials showed great potential as drug carriers for chemotherapeutics molecules due to their biocompatible physical and chemical properties. A manganese-based inorganic nanomaterial manganese phosphate (MnP) had become a new drug carrier in cancer therapy. However, the approach for manganese phosphate preparation and drug integration is still confined in complex methods. Inspired by mimetic mineralization, we proposed a "one-step" method for the preparation of manganese phosphate-doxorubicin (DOX) nanomedicines (MnP-DOX) by manganese ion and DOX complexation. The structural characterization results revealed that the prepared MnP-DOX nanocomplexes were homogeneous with controlled sizes and shapes. More importantly, the MnP-DOX nanocomposites could significantly induce cancer inhibition in vitro and in vivo. The results indicated that the drug molecules were integrated into MnP nanocarriers by mimetic mineralization, which not only prevented the premature release of the drug but also reduced excessive modification. Moreover, the designed MnP-DOX complex showed high loading efficacy and pH-dependent degradation leading to drug release, achieving high efficiency for cancer chemotherapy in vitro and in vivo via a facile process. These achievements presented an approach to construct the manganese phosphate-based chemotherapy nanomedicines by mimetic mineralization for cancer therapy.

Silk Fibroin/Collagen Blended Membrane Fabricated via a Green Papermaking Method for Potential Guided Bone Regeneration Application: In Vitro and In Vivo Evaluation.

Guided bone regeneration (GBR) technology is a commonly used surgical procedure for the repair of damaged periodontal tissues. Poor mechanical property and rapid degradation rate are the major reasons for GBR membrane failure in clinical applications. Herein, we applied a green papermaking method to fabricate silk fibroin (SF) membranes blended with collagen and tested their performance. The results showed that the blended SF75 (SF and collagen in a weight ratio of 75:25) membranes are biocompatible with good mechanical properties in the wet condition and appropriate biodegradation rate. MC3T3-E1 osteoblast cell adhesion and proliferation on the membranes were improved by the hybrid biological functions of SF and collagen. Subcutaneous implantation in rats for 9 weeks demonstrated that the membranes induced a less severe inflammatory response. The biodegradation time of the SF75 membranes was appropriate for tissue regeneration. This research, for the first time, reports a blended membrane prepared from silk fibroin and collagen with an ecofriendly method, which shows promise for application in guided bone regeneration.

siRNA-Loaded Hydroxyapatite Nanoparticles for KRAS Gene Silencing in Anti-Pancreatic Cancer Therapy.

Pancreatic carcinoma (PC) is greatly induced by the KRAS gene mutation, but effective targeted delivery for gene therapy has not existed. Small interfering ribonucleic acid (siRNA) serves as an advanced therapeutic modality and holds great promise for cancer treatment. However, the development of a non-toxic and high-efficiency carrier system to accurately deliver siRNA into cells for siRNA-targeted gene silencing is still a prodigious challenge. Herein, polyethylenimine (PEI)-modified hydroxyapatite (HAp) nanoparticles (HAp-PEI) were fabricated. The siRNA of the KRAS gene (siKras) was loaded onto the surface of HAp-PEI via electrostatic interaction between siRNA and PEI to design the functionalized HAp-PEI nanoparticle (HAp-PEI/siKras). The HAp-PEI/siKras was internalized into the human PC cells PANC-1 to achieve the maximum transfection efficiency for active tumor targeting. HAp-PEI/siKras effectively knocked down the expression of the KRAS gene and downregulated the expression of the Kras protein in vitro. Furthermore, the treatment with HAp-PEI/siKras resulted in greater anti-PC cells' (PANC-1, BXPC-3, and CFPAC-1) efficacy in vitro. Additionally, the HAp-PEI exhibited no obvious in vitro cytotoxicity in normal pancreatic HPDE6-C7 cells. These findings provided a promising alternative for the therapeutic route of siRNA-targeted gene engineering for anti-pancreatic cancer therapy.

Facile synthesis of biocompatible magnetic titania nanorods for T1-magnetic resonance imaging and enhanced phototherapy of cancers.

Cancer treatment has been recently energized by nanomaterials that simultaneously offer diagnostic and therapeutic effects. Among the imaging and treatment modalities in frontline research today, magnetic resonance imaging (MRI) and phototherapy have gained significant interest due to their noninvasiveness among other intriguing benefits. Herein, Fe(iii) was adsorbed on titanium dioxide to develop magnetic Fe-TiO2 nanocomposites (NCs) which leverage the Fe moiety in a double-edge-sword approach to: (i) achieve T1-weighted MRI contrast enhancement, and (ii) improve the well-established photodynamic therapeutic efficacy of TiO2 nanoparticles. Interestingly, the proposed NCs exhibit classic T1 MRI contrast agent properties (r1 = 1.16 mM-1 s-1) that are comparable to those of clinically available contrast agents. Moreover, the NCs induce negligible cytotoxicity in traditional methods and show remarkable support to the proliferation of intestine organoids, an advanced toxicity evaluation system based on three-dimensional organoids, which could benefit their potential safe application for in vivo cancer theranostics. Aided by the Fenton reaction contribution of the Fe component of the Fe-TiO2 NCs, considerable photo-killing of cancer cells is achieved upon UV irradiation at very low (2.5 mW cm-2) intensity in typical cancer PDT. It is therefore expected that this study will guide the engineering of other biocompatible magnetic titania-based nanosystems with multi-faceted properties for biomedical applications.

A Hybrid Organo-Nanotheranostic Platform of Superlative Biocompatibility for Near-Infrared-Triggered Fluorescence Imaging and Synergistically Enhanced Ablation of Tumors.

The quest for an all-organic nanosystem with negligible cytotoxicity and remarkable in vivo tumor theranostic capability is inescapably unending. Hitherto, the landscape of available photothermal agents is dominated by metal-based nanoparticles (NPs) with attendant in vivo negatives. Here, an all-organic-composed theranostic nanosystem with outstanding biocompatibility for fluorescence image-guided tumor photothermal therapy, and as a potential alternative to metal-based photothermal agents is developed. This is rationally achieved by compartmentalizing indocyanine green (ICG) in glycol chitosan (GC)-polypyrrole (PP) nanocarrier to form hybrid ICG@GC-PP NPs (≈65 nm). The compartmentalization strategy, alongside the high photothermal conversion ability of PP jointly enhances the low photostability of free ICG. Advantageously, ICG@GC-PP is endowed with an impeccable in vivo performance by the well-known biocompatibility track records of its individual tri organo-components (GC, PP, and ICG). As a proof of concept, ICG@GC-PP NPs enables a sufficiently prolonged tumor diagnosis by fluorescence imaging up to 20 h post-injection. Furthermore, owing to the complementary heating performances of PP and ICG, ICG@GC-PP NPs-treated mice by one-time near-infrared irradiation exhibit total tumor regression within 14 days post-treatment. Therefore, leveraging the underlying benefits of this study will help to guide the development of new all-organic biocompatible systems in synergism, for safer tumor theranostics.