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In recent years, the advancement of nanoparticle-based immunotherapy has introduced an innovative strategy for combatting diseases. Compared with other types of nanoparticles, protein nanoparticles have obtained substantial attention owing to their remarkable biocompatibility, biodegradability, ease of modification, and finely designed spatial structures. Nature provides several protein nanoparticle platforms, including viral capsids, ferritin, and albumin, which hold significant potential for disease treatment. These naturally occurring protein nanoparticles not only serve as effective drug delivery platforms but also augment antigen delivery and targeting capabilities through techniques like genetic modification and covalent conjugation. Motivated by nature's originality and driven by progress in computational methodologies, scientists have crafted numerous protein nanoparticles with intricate assembly structures, showing significant potential in the development of multivalent vaccines. Consequently, both naturally occurring and de novo designed protein nanoparticles are anticipated to enhance the effectiveness of immunotherapy. This review consolidates the advancements in protein nanoparticles for immunotherapy across diseases including cancer and other diseases like influenza, pneumonia, and hepatitis.

Herein, the vitamin K 2 (VK 2 )/maleimide (MA) coloaded mesoporous silica nanoparticles (MSNs), functional molecules including folic acid (FA)/triphenylphosphine (TPP)/tetrapotassium hexacyanoferrate trihydrate (THT), as well as CaCO 3 are explored to fabricate a core-shell-corona nanoparticle (VMM FTT C) for on-demand anti-tumor immunotherapy. After application, the tumor-specific acidic environment first decomposed CaCO 3 corona, which significantly levitates the pH value of tumor tissue to convert M2 type macrophage to the antitumor M1 type. The resulting VMM FTT would then internalize in both tumor cells and macrophages via FA-assisted endocytosis and free endocytosis, respectively. These distinct processes generate different amount of VMM FTT in above two cells followed by 1) TPP-induced accumulation in the mitochondria, 2) THT-mediated effective capture of various signal ions to cut off signal transmission and further inhibit glutathione (GSH) generation, 3) ions catalyzed reactive oxygen species (ROS) production through Fenton reaction, 4) sustained release of VK 2 and MA to further enhance the ROS production and GSH depletion, which caused significant apoptosis of tumor cells and additional M2-to-M1 macrophage polarization via different processes of oxidative stress. Moreover, the primary tumor apoptosis further matures surrounding immature dendritic cells and activates T cells to continuously promote the antitumor immunotherapy., (© 2023 Wiley‐VCH GmbH.)

Background: Lines of evidence indicated that, immune checkpoints (ICs) inhibitors enhanced T cell immune response to exert anti-tumor effects. However, T cell exhaustion has been so far a major obstacle to antitumor immunotherapy in colorectal cancer patients. Our previous studies showed that ginseng-derived nanoparticles (GDNPs) inhibited the growth of various tumors by reprograming tumor-associated macrophages (TAMs) and downregulated the ICs expression on T cells in tumor microenvironment (TME), but the underlying effector mechanisms remained unclear., Methods: The correlation between arginase-1 (ARG1) and T cells was computed based on the colorectal cancer patients in TCGA database. In vitro, we observed that GDNPs reprogrammed TAMs inhibited ARG1 release and ultimately ameliorated T cell exhaustion according to several techniques including WB, PCR, ELISA and flow cytometry. We also used an in vivo MC38 tumor-bearing model and administered GDNPs to assess their anti-tumor effects through multiple indices. The mechanism that GDNPs improved T cell exhaustion was further clarified using the bioinformatics tools and flow cytometry., Results: GDNPs reprogramed TAMs via reducing ARG1 production. Moreover, normalized arginine metabolism ameliorated T cell exhaustion through mTOR-T-bet axis, resulting in reduced ICs expression and enhanced CD8 + T cells expansion., Conclusions: By regulating the mTOR-T-bet axis, GDNPs reprogramed macrophages to regulate ARG1 release, which further ameliorated T cell exhaustion in TME. These findings provided new insights into comprehending the mechanisms underlying the mitigation of T cell exhaustion, which may facilitate the development of innovative therapeutic strategies in the field of cancer treatment., (© 2023. The Author(s).)

The excessive copper in tumor cells is crucial for the growth and metastasis of malignant tumor. Herein, we fabricated a nanohybrid to capture, convert and utilize the overexpressed copper in tumor cells, which was expected to achieve copper dependent photothermal damage of primary tumor and copper-deficiency induced metastasis inhibition, generating accurate and effective tumor treatment. The nanohybrid consistsed of 3-azidopropylamine, 4-ethynylaniline and N-aminoethyl-N'-benzoylthiourea (BTU) co-modified gold nanoparticles (AuNPs). During therapy, the BTU segment would specifically chelate with copper in tumor cells after endocytosis to reduce the intracellular copper content, causing copper-deficiency to inhibit the vascularization and tumor migration. Meanwhile, the copper was also rapidly converted to be cuprous by BTU, which further catalyzed the click reaction between azido and alkynyl on the surface of AuNPs, resulting in on-demand aggregation of these AuNPs. This process not only in situ generated the photothermal agent in tumor cells to achieve accurate therapy avoiding unexpected damage, but also enhanced its retention time for sustained photothermal therapy. Both in vitro and in vivo results exhibited the strong tumor inhibition and high survival rate of tumor-bearing mice after application of our nanohybrid, indicating that this synergistic therapy could offer a promising approach for malignant tumor treatment. STATEMENT OF SIGNIFICANCE: The distinctive excessive copper in tumor cells is crucial for the growth and metastasis of tumor. Therefore, we fabricated intelligent gold nanoparticles to simultaneously response and reverse this tumorigenic physiological microenvironment for the synergistic therapy of malignant tumor. In this study, for the first time we converted and utilized the overexpressed Cu 2+ in tumor cells to trigger intracellular click chemistry for tumor-specific photothermal therapy, resulting in accurate damage of primary tumor. Moreover, we effectively manipulated the content of Cu 2+ in tumor cells to suppress the migration and vascularization of malignant tumor, resulting in effective metastasis inhibition., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Tumor recurrence caused by metastasis is a major cause of death for patients. Thus, a strategy to manipulate the circulating tumor cells (CTCs, initiators of tumor metastasis ) and eliminate them along with the primary tumor has significant clinical significance for malignant tumor therapy. In this study, a magnet-NIR-pH multi-responsive nanosheet (Fe 3 O 4 @SiO 2 -GO-PEG-FA/AMP-DOX, FGPFAD ) was fabricated to capture CTCs in circulation, then magnetically transport them to the primary tumor, and finally perform NIR-dependent photothermal therapy as well as acidic-environment-triggered chemotherapy to destroy both the CTCs and the primary tumor. The FGPFAD nanosheet consists of silica-coated ferroferric oxide nanoparticles (Fe 3 O 4 @SiO 2 , magnetic targeting agent), graphene oxide (GO, photothermal therapy agent), polyethylene glycol (PEG, antifouling agent for sustained circulation), folic acid (FA, capturer of CTCs) and antimicrobial-peptide-conjugated doxorubicin (AMP-DOX, agent for chemotherapy), in which the AMP-DOX was bound to the FGPFAD nanosheet via a cleavable Schiff base to achieve acidic-environment-triggered drug release for tumor-specific chemotherapy. Both in vitro and in vivo results indicated that the effective capture and magnetically guided transfer of CTCs to the primary tumor, as well as the multimodal tumor extermination performed by our FGPFAD nanosheet, significantly inhibited the primary tumor and its metastasis.

Magnetic resonance (MR) imaging techniques, which can provide images with excellent anatomical detail, are widely used in clinical diagnosis. However, the current clinical small molecule gadolinium (Gd) contrast agents have the defects of relatively low sensitivity and poor tumor-target specificity, preventing their adoption in biology and medicine. Herein, a facile synthetic strategy to fabricate gadolinium-hybridized mesoporous organosilica nanoparticles (MOSG) through a nanoprecipitation reaction, with the surface of nanoparticles grafted with the fluorescent dye isothiocyanate (FITC) and arginine-glycine-aspartic acid (RGD) for delivery of the antitumour drug doxorubicin hydrochloride (DOX), resulting in a high-performance nanotheranostic (RGD-MOSG-FITC/DOX) for targeted magnetic resonance imaging and chemotherapy of tumors. The prepared MOSG had a particle size of 60-80 nm and gadolinium elements were distributed in clusters that exhibited boosted longitudinal relaxivity. Routine blood tests and histopathology indicated good biocompatibility of MOSG. Furthermore, after being decorated with Arg-Gly-Asp peptide (RGD), RGD-MOSG-FITC demonstrated more preferable cellular uptake by HeLa cells (high expression of α Ⅴ β 3 ) than MOSG without RGD grafting. Additionally, the tumor growth inhibition effect of RGD-MOSG-FITC/DOX was substantially more effective than that of the other groups. Therefore, this new delivery platform has good application potential in the field of tumor diagnosis and treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The elasticity of nanoparticles plays a critical role in regulating nanoparticle-biosystem interactions. However, the elasticity of traditional organic-based carriers can only be regulated within a narrow range, and the effects of elasticity on in vivo biological processes have not been evaluated until now. Here, we construct hyaluronic acid modified mesoporous organosilica nanoparticles (MONs-HA) with a wide range of elasticity by an interior preferential etching approach and investigate the impact of their elasticity on in vitro cellular uptake, in vivo blood circulation, and tumor accumulation. The Young's moduli of the prepared MONs-HA are 1.64, 0.93, 0.78, 0.4 and 0.29 GPa (denoted as rigid MONs 0 -HA, semi-elastic MONs 20 -HA and MONs 50 -HA, elastic MONs 100 -HA and MONs 200 -HA), respectively. They all possess a similar hydrodynamic size (245-257 nm), similar surface electronegativity (-27 to -35 mV), and excellent dispersibility. In vitro experiments demonstrate that the elastic MONs 100 -HA and MONs 200 -HA (0.4 and 0.29 GPa) exhibit significantly greater cellular uptake relative to semi-elastic MONs 20 -HA and MONs 50 -HA (0.93 and 0.78 GPa) or rigid MONs 0 -HA (1.64 GPa). Simultaneously, these elastic MONs 100 -HA and MONs 200 -HA show an efficiently prolonged circulation time. In vivo results revealed that the elastic MONs 100 -HA show enhanced tumor accumulation compared to semi-elastic and rigid MONs-HA after intravenous administration. These desirable features of elasticity can direct the design of nanoplatforms, leading to an enhanced tumor delivery efficiency.

Introduction: Photodynamic therapy (PDT) has attracted increasing attention for tumor treatment because of its minimal invasiveness and specific spatiotemporal selectivity. However, insufficient tumor accumulation and low cellular uptake of photosensitizers limit its therapeutic efficacy., Methods: In this study, flexible hollow human serum albumin/catalase nanocapsules (HSA/CATs) were created using a core-assisted protein-coating method and combined with the photosensitizer chlorin e6 (HSA/CAT@Ce6) for PDT., Results and Discussion: Transmission electron microscopy (TEM) images demonstrate that HSA/CAT nanocapsules are flexible, with a uniform diameter (310 nm) and a well-defined hollow structure. Thanks to their flexibility, HSA/CAT@Ce6 nanocapsules show a higher cellular uptake than rigid nanoparticles. The nanocapsules effectively generate reactive oxygen species (ROS) in 4T1 cells because of their high cellular uptake and catalytic capacity, remarkably enhancing their in vitro PDT efficacy. In addition, the in vivo tumor accumulation of HSA/CAT@Ce6 nanocapsules is significantly larger than that of rigid nanoparticles and Ce6, meaning they are highly effective in tumor cell ablation. This demonstrates that our flexible nanoplatform holds great promise for enhancing PDT of tumor., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Shi et al.)

Petroleum-based synthetic flame-proof fiber releases toxic volatile organic compounds in thermal decomposition process and has other problems, like tickling feeling and high density. A natural polysaccharide, calcium alginate, is an intrinsic fire-resistant biodegradable material, but its limited mechanical performance prevents it from being a practical flame-retardant fabric. To address this problem, Na 2 CO 3 was doped into alginate spinning solution to obtain in situ generating CaCO 3 nanoparticle-reinforced alginate fiber by microfluidic spinning technique. Comparative analysis illustrated that incorporation of 0.50% Na 2 CO 3 into the fiber greatly improved its mechanical performance; meanwhile, in situ generated CaCO 3 nanoparticles also throttled oxygen and heat flow in burning, endowing the fiber with excellent flame retardancy. The prepared composite fiber released less heat, smoke, and toxic volatile organic compounds in burning, which reduced the fire hazard. The formed residue char and pyrolysis products functioned as the physical barrier and displayed a synergistic effect to inhibit oxygen and heat transmission and impede the further combustion. All of the results demonstrate that the obtained fiber exhibits a good mechanical and flame-retardant performance, making it an ideal candidate as a fire-protection textile.

Background: Due to their prevalence, dental caries ranks first among all diseases endangering human health. Therefore, the prevention of caries is of great significance, as caries have become a serious public health problem worldwide. Currently, using nanoscale drug delivery systems to prevent caries has received increased attention. However, the preventive efficacy of these systems is substantially limited due to the unique physiological structure of cariogenic biofilms. Thus, novel strategies aimed at combating cariogenic biofilms to improve preventive efficiency against caries are meaningful and very necessary. Herein, inspired by cell membrane coating technology and Lactobacillus strains, we coated triclosan (TCS)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TCS@PLGA-NPs) with an envelope of Lactobacillus (LA/TCS@PLGA-NPs) and investigated their potential as a nanoparticle delivery system against cariogenic biofilms and dental caries., Results: LA/TCS@PLGA-NPs were successfully prepared with favorable properties, including a coated envelope, controllable size, negative charge, sustained drug-release kinetics and so on. The LA/TCS@PLGA-NPs inherited native properties from the source cell surface, thus the LA/TCS@PLGA-NPs adhered to S. mutans, integrated into the S. mutans biofilm, and interfered with the biofilm formation of S. mutans. The nanoparticles significantly inhibited the activity, biomass and virulence gene expression of S. mutans biofilms in vitro. Additionally, LA/TCS@PLGA-NPs exhibited a long-lasting inhibitory effect on the progression of caries in vivo. The safety performance of the nanoparticles is also favorable., Conclusions: Our findings reveal that the antibiofilm effect of LA/TCS@PLGA-NPs relies not only on the inheritance of native properties from the Lactobacillus cell surface but also on the inhibitory effect on the activity, biomass and virulence of S. mutans biofilms. Thus, these nanoparticles could be considered feasible candidates for a new class of effective drug delivery systems for the prevention of caries. Furthermore, this work provides new insights into cell membrane coating technology and presents a novel strategy to combat bacterial biofilms and associated infections., (© 2022. The Author(s).)

Tumorigenic environments, especially aberrantly overexpressed oncogenic microRNAs, play a critical role in various activities of tumor progression. However, developing strategies to effectively utilize and manipulate these oncogenic microRNAs for tumor therapy is still a challenge. To address this challenge, spherical nucleic acids (SNAs) consisting of gold nanoparticles in the core and antisense oligonucleotides as the shell are fabricated. Hybridized to the oligonucleotide shell is a DNA sequence to which doxorubicin is conjugated (DNA-DOX). The oligonucleotides shell is designed to capture overexpressed miR-21/miR-155 and inhibit the expression of these oncogenic miRNAs in tumor cells after tumor accumulation to manipulate genetic environment for accurate gene therapy. This process further induces the aggregation of these SNAs, which not only generates photothermal agents to achieve on-demand photothermal therapy in situ, but also enlarges the size of SNAs to enhance the retention time in the tumor for sustained therapy. The capture of the relevant miRNAs simultaneously triggers the intracellular release of the DNA-DOX from the SNAs to deliver tumor-specific chemotherapy. Both in vivo and in vitro results indicate that this combination strategy has excellent tumor inhibition properties with high survival rate of tumor-bearing mice, and can thus be a promising candidate for effective tumor treatment., (© 2022 Wiley-VCH GmbH.)

Herein, a feasible outside-in hydrothermal self-transformation strategy is presented to fabricate hierarchically porous benzene-bridged organosilica nanoparticles (HPBONs), and detailed mechanistic investigations were performed to study the formation of hierarchically porous nanostructures. The obtained HPBONs consisted of a mesoporous core (2.3 nm) and a large mesoporous flocculent shell (12.6 nm), which corresponded to an overall diameter of ∼ 200 nm and good water dispersibility, respectively. Owing to the unique hierarchically porous structure and high surface area (877 m 2 /g), HPBONs showed a high coloading capacity for the hydrophilic drug doxorubicin (DOX) and the hydrophobic photosensitizer chlorin e6 (Ce6) (355 µg/mg, 38 µg/mg, respectively) and acid-responsive DOX drug release (42.62%), leading to precise chemo-photodynamic therapy in vitro, as the cytotoxicity assay revealed 70% killing of breast cancer (MCF-7) cells. This research provides a new method to construct hierarchically porous organosilica-based nanodelivery systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Cold tumor microenvironment (TME) marked with low effector T cell infiltration leads to weak response to immune checkpoint inhibitor (ICI) treatment. Thus, switching cold to hot TME is critical to improve potent ICI therapy. Previously, we reported extracellular vesicle (EV)-like ginseng-derived nanoparticles (GDNPs) that were isolated from Panax ginseng C.A. Mey and can alter M2 polarization to delay the hot tumor B16F10 progression. However, the cold tumor is more common and challenging in the real world. Here, we explored a combinatorial strategy with both GDNPs and PD-1 (programmed cell death protein-1) monoclonal antibody (mAb), which exhibited the ability to alter cold TME and subsequently induce a durable systemic anti-tumor immunity in multiple murine tumor models. GDNPs enhanced PD-1 mAb anti-tumor efficacy in activating tumor-infiltrated T lymphocytes. Our results demonstrated that GDNPs could reprogram tumor-associated macrophages (TAMs) to increase CCL5 and CXCL9 secretion for recruiting CD8 + T cells into the tumor bed, which have the synergism to PD-1 mAb therapy with no detected systemic toxicity. In situ activation of TAMs by GDNPs may broadly serve as a facile platform to modulate the suppressive cold TME and optimize the PD-1 mAb immunotherapy in future clinical application., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

The synergy of chemodynamic therapy (CDT) and photothermal therapy (PTT) can improve anticancer efficacy, while the limited diffusion distance and the short lifetime of • OH still greatly restrict the therapeutic efficacy of PTT-CDT. Herein, MoS 2 @PDA-Fe@PEG/TPP (MPFPT) nanosheets (NSs) with mitochondria-targeting ability were reported for enhanced PTT-CDT synergistic oncotherapy. MPFPT NSs were prepared by covalent modification of poly(ethylene glycol) (PEG) and triphenylphosphonium (TPP) on polydopamine (PDA)-Fe 3+ coated MoS 2 NSs. Co-localization experiments showed that MPFPT NSs can efficiently target mitochondria via the direction of TPP. Moreover, MPFPT NSs have good photothermal performance in the second near-infrared (NIR-II) region and can greatly accelerate the Fenton reaction from H 2 O 2 to generate more hydroxyl radicals ( • OH). In vitro experimental results showed that MPFPT NSs have improved therapeutic efficacy to cancer cells than similar MoS 2 -based nanoagents without mitochondria-targeting units, which can be attributed to the short distance between mitochondria and MPFPT NSs and the efficient damage of mitochondria by in situ generated • OH. In the 4T1 tumor-bearing mice model, MPFPT NSs demonstrated significantly enhanced therapeutic efficacy by PTT-CDT, suggesting the superiority of the mitochondria-targeting strategy. This study reveals that mitochondria-targeting MPFPT NSs are promising nanoagents for oncotherapy.

The recurrence and metastasis of tumor after surgery is the main cause of death for patients with breast cancer. Systemic chemotherapy suffered from low delivery efficiency to tumors and the side effects of chemo drugs. Localized chemotherapy using drug-containing implants is an alternative, while the reconstruction of breast tissue is generally considered after chemotherapy, resulting in a second surgery for patients. Here, we describe a strategy using implantable drug-containing polymeric scaffolds to deliver chemo drugs directly to the post-resection site, and simultaneously provide mechanical support and regenerative niche for breast tissue reconstruction. When doxorubicin was loaded in mesoporous silica nanoparticles and subsequently incorporated into polycaprolactone scaffolds (DMSN@PCL), a 9-week sustained drug release was achieved post implantation in mice. The local recurrence of residual tumor after surgery was significantly inhibited within 4 weeks in a post-surgical mouse model bearing xenograft MDA-MB-231 tumor. DMSN@PCL scaffolds exhibited good biocompatibility in mice during the treatment. We believe our strategy holds great promise as an adjuvant localized chemotherapy in clinics for combating post-resection breast cancer recurrence.

Deformable materials have garnered widespread attention in biomedical applications. Herein, a controllable, general, and simple alkaline etching strategy was used to synthesize deformable hollow mesoporous organosilica nanocapsules (DMONs), in which multiple organic moieties were homogeneously incorporated into the framework. DMONs with double-, triple-, and even quadruple-hybridized frameworks were prepared by the selective introduction of organosilica precursors in accordance with the chemical homology principle through a surfactant-directed sol-gel procedure and a subsequent etching process in alkaline solution. The triple-hybridized DMONs possessed uniform and controllable diameters (100-330 nm), and large hollow cavities (50-270 nm). Liquid cell electron microscopy images demonstrated that the DMONs were deformable in solution. Elemental mapping images suggested that the organic components were homogeneous distribution within the entire DMONs framework. Statistical analysis of cell proliferation assays showed that breast cancer MCF-7 viability exceeded 85% when the cells are incubated with the triple-hybridized DMONs (800 μg mL -1 ) for 24 h. Histological assessments of main organs indicated no tissue injury or necrosis after intravenous injection of the DMONs 7 days (5 mg kg -1 body weight). Quantitative analysis indicated that the cellular uptake of the DMONs was 6-fold higher than that of their hard counterparts when the number of nanoparticles added was 1.25 × 10 4 , and similar results were found for 4 T1 cells. Furthermore, doxorubicin (DOX) loaded triple-hybridized DMONs with a loading efficiency of 16.9 wt%, produced a strong killing effect on tumor cells. Overall, DMONs with various incorporated organic functional groups could serve as novel nanoplatforms for drug delivery in biomedical applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Inc.)

A lipase-triggered drug release nanoplatform (PGL-DPP-FLU NPs) for multi-modal antifungal therapy is developed. The lipases secreted by C. albicans can accelerate FLU release. The ROS and heat produced by PGL-DPP-FLU NPs make C. albicans more vulnerable to FLU, thereby PGL-DPP-FLU NPs exhibit high performance for combating azole-resistant C. albicans biofilms and wound infection.

Antibacterial agents with high antibacterial efficiency and bacteria-binding capability are highly desirable. Herein, we describe the successful preparation of Cu 2 WS 4 nanocrystals (CWS NCs) with excellent antibacterial activity. CWS NCs with small size (∼20 nm) achieve more than 5 log (>99.999%) inactivation efficiency of both Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) at low concentration (<2 μg mL -1 ) with or without ambient light, which is much better than most of the reported antibacterial nanomaterials (including Ag, TiO 2 , etc .) and even better than the widely used antibiotics (vancomycin and daptomycin). Antibacterial mechanism study showed that CWS NCs have both enzyme-like (oxidase and peroxidase) properties and selective bacteria-binding ability, which greatly facilitate the production of reactive oxygen species to kill bacteria. Animal experiments further indicated that CWS NCs can effectively treat wounds infected with methicillin-resistant Staphylococcus aureus (MRSA). This work demonstrates that CWS NCs have the potential as effective antibacterial nanozymes for the treatment of bacterial infection.

Background: It is unclear whether plant-derived extracellular vesicles (EVs) can mediate interspecies communication with mammalian cells. Tumor-associated macrophages (TAMs) display a continuum of different polarization states between tumoricidal M1 phenotype and tumor-supportive M2 phenotypes, with a lower M1/M2 ratio correlating with tumor growth, angiogenesis and invasion. We investigated whether EVs from ginseng can alter M2-like polarization both in vitro and in vivo to promote cancer immunotherapy., Methods: A novel EVs-liked ginseng-derived nanoparticles (GDNPs) were isolated and characterized from Panax ginseng C. A. Mey. Using GDNPs as an immunopotentiator for altering M2 polarized macrophages, we analyzed associated surface markers, genes and cytokines of macrophages treated with GDNPs. Mice bearing B16F10 melanoma were treated with GDNPs therapy. Tumor growth were assessed, and TAM populations were evaluated by FACS and IF., Results: GDNPs significantly promoted the polarization of M2 to M1 phenotype and produce total reactive oxygen species, resulting in increasing apoptosis of mouse melanoma cells. GDNP-induced M1 polarization was found to depend upon Toll-like receptor (TLR)-4 and myeloid differentiation antigen 88 (MyD88)-mediated signaling. Moreover, ceramide lipids and proteins of GDNPs may play an important role in macrophage polarization via TLR4 activation. We found that GDNPs treatment significantly suppressed melanoma growth in tumor-bearing mice with increased presence of M1 macrophages detected in the tumor tissue., Conclusions: GDNPs can alter M2 polarization both in vitro and in vivo, which contributes to an antitumor response. The polarization of macrophages induced by GDNPs is largely dependent on TLR4 and MyD88 signalling. GDNPs as an immunomodulator participate in mammalian immune response and may represent a new class of nano-drugs in cancer immunotherapy.

The size effect of mesoporous organosilica nanoparticles (MONs) on tumor penetration and accumulation remains poorly understood, which strongly affects the tumor therapeutic efficacy. Herein, four different-sized thioether-bridged MONs (20, 40, 60, and 100 nm) are synthesized; all the MONs have a spherical morphology, excellent dispersity, similar surface charge, uniform mesopores (3.2-3.5 nm), and large surface areas (709-1353 m 2 ·g -1 ). Hematology and histopathology analyses demonstrate that the four MONs do not cause pathological changes in mice even at a dose of 20 mg kg -1 for 30 d. The penetration depth of the MONs for multicellular spheroids (MCSs) decreases with increasing particle sizes, and the 20 nm MONs are uniformly distributed in the MCSs at a depth of 60 μm, while the larger MONs are mainly restricted to peripheral areas. In vivo experiments show that the 40 nm MONs possess the longest mean residence times, leading to their highest accumulation in blood and tumors. However, the 20 nm MONs reach the deepest penetration depth of 1230 μm for xenograft tumors. In contrast, the penetration depths of 40, 60, and 100 nm MONs are 783, 105, and 40 μm, respectively. Overall, this work provides an important guideline for the rational design of nanoplatforms for tumor treatment.

A versatile and straightforward strategy for the encapsulation of semiconducting polymer nanoparticles (SPNs) using biocompatible polydopamine (PDA) as both the protection and versatile bioconjugation layer is proposed. In addition to providing stable functionalized SPNs, this approach provides SPNs with a flexible surface for further modification with various functional ligands. In this study, three representative surface modifiers including a small molecule (folic acid, FA), a peptide (cRGD) and a stealth polymer (SH-PEG) were conjugated onto the surface of SPNs. Specifically, PDA encapsulation can reliably form SPNs that are uniform in size (∼65 nm) and facilitate the rapid purification of SPN bioconjugates by centrifugation which is difficult to achieve using traditional methods for preparing SPN bioconjugates. Compared to pristine PSBTBT NPs, the synthesized PSBTBT@PDA NPs simultaneously showed more excellent structural stability, significantly enhanced PA brightness and amplified PTT efficacy. Benefiting from the outstanding PA and PTT performances, it is possible for the PSBTBT@PDA NPs to ablate tumors more effectively compared to PSBTBT NPs. Our study thus demonstrates that the PDA encapsulated SPNs should be a promising theranostic agent for PA imaging and PTT.

Intracellular detection of caspase-3 activity is crucial for the study of cell apoptosis and caspase-3 related diseases. Although various nanomaterials-based biosensors have been constructed for this purpose, they often suffer from poor stability or complicated construction due to the lack of a facile and efficient biofunctionalization method, which decreases their sensing performance and limits their use in the complex physiological environments. As novel two-dimentional (2D) nanomaterials, MoS 2 nanosheets (NSs) have shown great potential for biosensing due to their unique properties. Herein, we develop a versatile yet facile covalent biofucntionalization strategy of MoS 2 NSs by utilizing polydopamine (PDA) as nano-bio interface, and construct an intracellular fluorescent biosensor (MoS 2 @PDA-PEG-Peptide, MPPP) for the determination of caspase-3 activity. This covalent biofunctionalization of MoS 2 NSs can significantly improve the conjugation efficiency of biomolecules and enhance their stability in complicated environments, which is much better than conventional biofunctionalization by using thiol-metal coordination. Furthermore, this novel caspase-3 biosensor based on peptides biofunctionalized MoS 2 NSs shows high sensitivity and selectivity for the detection of caspase-3 with a limit of detection (LOD) of 0.33 ng/mL, and can be used for high-contrast fluorescent imaging of cell apoptosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Herein, a mesoporous organosilica nanoparticle (MON) based nanodrug highly loaded with cisplatin (CDDP) and doxorubicin (DOX) (denoted as MONs/CDDP/DOX) has been successfully prepared for the first time. The MONs are characterized with core-contained double hollow shells, thioether and ethane groups separately incorporated frameworks, uniform diameter (420 nm), large surface area (592 m 2 /g), and ordered pore size (2.5 nm). The safety evaluation of the MONs based on cell viability, haemolytic activity, histological change, and serum biochemical index demonstrates that they have excellent biological compatibility. The efficient uptake of the MONs by human breast cancer MCF-7 cells is further confirmed via confocal laser scanning imaging and flow cytometry. Importantly, the contents of CDDP and DOX in the MONs/CDDP/DOX nanodrug are as high as 120 mg/g and 85 mg/g, respectively. Therefore, the MONs/CDDP/DOX shows a significant improved killing effect against human breast cancer MCF-7 cells compared with sole DOX or CDDP loaded MONs, demonstating the promise of the nanodrug for cancer treatment., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The synthesis of mesoporous nanoparticles with controllable structure and organic groups is important for their applications. In this work, yolk-shell-structured periodic mesoporous organosilica (PMO) nanoparticles simultaneously incorporated with ethane-, thioether-, and benzene-bridged moieties are successfully synthesized. The preparation of the triple-hybridized PMOs is via a cetyltrimethylammonium bromide-directed sol-gel process using mixed bridged silsesquioxanes as precursors and a following hydrothermal treatment. The yolk-shell-structured triple-hybridized PMO nanoparticles have large surface area (320 m(2) g(-1) ), ordered mesochannels (2.5 nm), large pore volume (0.59 cm(3) g(-1) ), uniform and controllable diameter (88-380 nm), core size (22-110 nm), and shell thickness (13-45 nm). In vitro cytotoxicity, hemolysis assay, and histological studies demonstrate that the yolk-shell-structured triple-hybridized PMO nanoparticles have excellent biocompatibility. Moreover, the organic groups in the triple-hybridized PMOs endow them with an ability for covalent connection of near-infrared fluorescence dyes, a high hydrophobic drug loading capacity, and a glutathione-responsive drug release property, which make them promising candidates for applications in bioimaging and drug delivery., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Photothermal therapy (PTT) is a promising cancer treatment with both high effectiveness and fewer side effects. However, an ideal PTT agent not only needs strong absorption of near-infrared (NIR) light and high photothermal conversion efficiency, but also needs good biocompatibility, stability, and small size, which makes the design and preparation of a novel PTT agent a great challenge. In this work, we developed an ultrasonication-assisted liquid exfoliation method for the direct preparation of ultrasmall (2-3 nm) MoSe2 nanodots (NDs) in aqueous solution and demonstrated their superior properties as a PTT agent. The as-prepared MoSe2 NDs have strong absorption of NIR light and high photothermal conversion efficiency of about 46.5%. In vitro cellular experiments demonstrate that MoSe2 NDs have negligible cytotoxicity and can efficiently kill HeLa cells (human cervical cell line) under NIR laser (785 nm) irradiation.

A facile and efficient strategy to prepare multicolor and surface-functionalizable conjugated polymer nanoparticles (PPVseg-COOH CPNs) was demonstrated. The CPNs with tunable photoluminescence colors and carboxylate groups were further covalently modified with a series of specific molecules such as streptavidin, IgG and poly(ethylene glycol) to show their generality for subsequent bioconjugation and biological applications. The streptavidin coating can significantly improve the photostability of the PPVseg-SA CPNs, which indicates that specific biomolecules such as streptavidin functionalization of multicolor PPVseg-COOH CPNs can be applied to achieve high optical stability of CPNs in various buffer solutions, metal ions for many biological applications. Furthermore, the resulted PPVseg-SA CPNs also show efficient labeling ability in specific cellular imaging. The synthetic methods present the feasibility and versatility for further developing surface-functionalizable CPNs probes with full-color tunability for biological imaging and bioanalytical applications.

The authors demonstrate a smart and versatile approach for preparing multi-spectral conjugated polymers from a commercial precursor MEH-PPV without tedious synthetic modification. Multi-color CPNs with small size have also been successfully prepared using a modified-reprecipitation procedure for live cell imaging.

In this work, data for the interactions between humic acid (HA) or fulvic acid (FA) with phosphate ions at the surface of goethite (alpha-FeOOH) are presented. The results show very clear differences between HA and FA in their interactions with phosphate at goethite surface. HA is strongly bound to goethite but surprisingly does not strongly affect the phosphate binding, whereas FA is less strongly bound, but these molecules have a very large effect on the phosphate adsorption, and vice versa. Phosphate adsorption to goethite in the presence of adsorbed HA or FA can be well predicted with the LCD model (ligand and charge distribution). According to the model calculations, the nature of the interactions between HA or FA with phosphate at goethite surface is mainly electrostatic. The stronger effects of FA on phosphate adsorption are caused by its spatial location which is closer to the oxide surface, and as a consequence, the electrostatic interactions between adsorbed FA particles and phosphate ions are much stronger than for HA particles. This is the first time that effects of natural organic matter (NOM) on an anion adsorption are predicted successfully using an integrated ion-binding model for oxides and for humics that accounts for chemical heterogeneity of NOM.

The composite nanoparticles and corresponding self-reinforcing composites comprising tricalcium phosphate (TCP) and alumina (Al2O3) were synthesized by simultaneous precipitation from the CaCl2, AlCl3 and (NH4)2HPO4 aqueous solutions, using aqueous NH4OH as precipitant. Influences of the precipitating media pH and the Ca/P atomic ratios on phase composition and morphology of the composites were investigated. Results showed that except for the major phases β-TCP and α-Al2O3, there was always a third minor phase in the calcined composites coprecipitated either in neutral or alkaline condition. Formation of β-TCP is, however, favored at pH 9.2, whereas more of the third phase, mainly AlPO4, is formed under neutral condition. High Ca/P ratios suppress the formation of α-Al2O3 phase under alkaline precipitating condition, but the effect is less significant in neutral condition. TEM observation showed that the ‘as prepared’ composite particles are nano-sized but interconnected to form a network-like morphology. They were changed to a core-shell-like structure after calcination, while their nano-scale dimension was retained. FEGSEM analysis revealed that the α-Al2O3 phase in the sintered composite compacts was in the form of fibrils dispersed in the phosphate phases. These in situ formed fibrils impart a unique role in self-reinforcement of the sintered composites. Mechanical measurements showed that the incorporation of alumina reinforced β-TCP effectively: the flexural strength increased from 15 MPa of the pure β-TCP to 84 MPa of the composite with 40 wt% of α-Al2O3. [ABSTRACT FROM AUTHOR]