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Improving the performance of nanocarriers remains a major challenge in the clinical translation of nanomedicine. Efforts to optimize nanoparticle formulations typically rely on tuning the surface density and thickness of stealthy polymer coatings such as poly(ethylene glycol) (PEG). Here, we show that modulating the surface topography of PEGylated nanoparticles using bottlebrush block copolymer (BBCP) significantly enhances circulation and tumor accumulation providing an alternative strategy to improve nanoparticle coatings. Specifically, nanoparticles with rough surface topography achieve high tumor cell uptake in vivo due to superior tumor extravasation and distribution compared to conventional smooth-surfaced nanoparticles. Furthermore, surface topography profoundly impacts the interaction with serum proteins resulting in the adsorption of fundamentally different proteins onto the surface of rough-surfaced nanoparticles formed from BBCPs. We envision that controlling the nanoparticle surface topography of PEGylated nanoparticles will enable the design of improved nanocarriers in various biomedical applications.

Few studies have investigated whether dual sensory impairment (DSI) adversely affects the deterioration of physical function in older adults compared to single sensory impairment (SSI, visual or auditory). We studied the association between DSI and declining physical function by analyzing the data of 2780 Korean community-dwelling adults aged 70–84 years. Sensory impairment was assessed through pure tone audiometry and visual acuity testing. Muscle strength (handgrip strength) and physical performance (timed up and go test and short physical performance battery (SPPB)) were evaluated. In the cross-sectional analysis, DSI was associated with higher odds of having low muscle strength (odds ratio (OR), 1.78; 95% confidence interval (CI), 1.27–2.48) and poor physical performance (SPPB: OR, 2.04; 95% CI, 1.38–3.00) than SSI. Among all sensory impairment groups in the longitudinal analysis, DSI at baseline increased the risk of deteriorating physical performance during the follow-up period (OR, 1.94; 95% CI, 1.31–2.88; p < 0.01) the most. DSI showed a more severe adverse effect on the decline in physical function among community-dwelling older adults than SSI. More comprehensive care is needed to prevent the deterioration of physical function in older adults due to DSI.

Understanding the rationale of combining immunotherapy and other anticancer treatment modalities is of great interest because of interpatient variability in single-agent immunotherapy. Here, we demonstrated that topoisomerase I inhibitors, a class of chemotherapeutic drugs, can alter the tumor immune landscape, corroborating their antitumor effects combined with immunotherapy. We observed that topotecan-conditioned TC-1 tumors were occupied by a vast number of monocytic cells that highly express CD11c, CD64, and costimulatory molecules responsible for the favorable changes in the tumor microenvironment. Ly6C+MHC-II+CD11chiCD64hi cells, referred to as topotecan-induced monocyte-derived dendritic cells (moDCs), proliferate and activate antigen-specific CD8+ T cells to levels equivalent to those of conventional DCs. Phenotypic changes in Ly6C+ cells towards moDCs were similarly induced by exposure to topotecan in vitro, which was more profoundly facilitated in the presence of tumor cells. Notably, anti-M-CSFR reversed the acquisition of DC-like properties of topotecan-induced moDCs, leading to the abolition of the antitumor effect of topotecan combined with a cancer vaccine. In short, topoisomerase I inhibitors generate monocyte-derived antigen-presenting cells in tumors, which could be mediated by M-CSF-M-CSFR signaling.

Smart home to provide various automated services based on the Internet of Things for residents should design a new value of residential space by connecting various services through an integrated platform. However, there are few studies highlighting the value-based network in the smart home industry yet. Therefore, this study finds determinants of a value-based network (rather than an actor-based network) within smart home industries, conducting logistic and negative binomial regressions with survey data of 300 firms in the Korean SHOME industry. This study proposes an evolved innovation system for SHOME industry, based on a value-based innovation system. The results of this study suggest the effects of each value group network and value network on open innovation in SHOME industry and their implications.

The photoluminescence (PL) of metal nanoclusters (NCs), originating from their molecule-like electronic structure, is one of the most intriguing properties of NCs. Although various strategies such as tailoring the size, structure, and chemical environment of NCs have shown to improve the PL, their quantum yields (QYs) are still lagging far behind those of conventional luminescent materials, including quantum dots and organic fluorophores. Herein, we report the synthesis of highly luminescent gold cluster assembly (GCA) from Zn2+-ion-mediated assembly of Au4(SRCOO-)4 clusters using mercaptocarboxylic acid as a protective ligand and reductant as well as a growth suppressor. The synergetic combination of unique aurophilic interactions among Au4 clusters and the rigidified chemical environment induced by metal ion chelation through carboxylate groups is responsible for the ultrabright greenish-blue fluorescence with a QY up to 90%. Furthermore, the unique flexibility of dis/reassembly and the aggregation-dependent strong fluorescence of GCA offer a great potential for applications in biodegradable and trackable drug delivery systems.

An inhalable platform for mRNA therapeutics would enable minimally invasive and lung targeted delivery for a host of pulmonary diseases. Development of lung targeted mRNA therapeutics has been limited by poor transfection efficiency and risk of vehicle-induced pathology. Here we report an inhalable polymer-based vehicle for delivery of therapeutic mRNAs to the lung. We optimized biodegradable poly(amine-co-ester) polyplexes for mRNA delivery using end group modifications and polyethylene glycol. Our polyplexes achieved high transfection of mRNA throughout the lung, particularly in epithelial and antigen-presenting cells. We applied this technology to develop a mucosal vaccine for SARS-CoV-2. Intranasal vaccination with spike protein mRNA polyplexes induced potent cellular and humoral adaptive immunity and protected K18-hACE2 mice from lethal viral challenge.One-sentence summaryInhaled polymer nanoparticles (NPs) achieve high mRNA expression in the lung and induce protective immunity against SARS-CoV-2.

Poly(ethylene glycol) (PEG) is widely employed for passivating nanoparticle (NP) surfaces to prolong blood circulation and enhance localization of NPs to target tissue. However, the immune response of PEGylated NPs-including anti-PEG antibody generation, accelerated blood clearance (ABC), and loss of delivery efficacy-is of some concern, especially for treatments that require repeat administrations. Although polyglycerol (PG), which has the same ethylene oxide backbone as PEG, has received attention as an alternative to PEG for NP coatings, the pharmacokinetic and immunogenic impact of PG has not been studied systematically. Here, linear PG, hyperbranched PG (hPG), and PEG-coated polylactide (PLA) NPs with varying surface densities were studied in parallel to determine the pharmacokinetics and immunogenicity of PG and hPG grafting, in comparison with PEG. We found that linear PG imparted the NPs a stealth property comparable to PEG, while hPG-grafted NPs needed a higher surface density to achieve the same pharmacokinetic impact. While linear PG-grafted NPs induced anti-PEG antibody production in mice, they exhibited minimal accelerated blood clearance (ABC) effects due to the poor interaction with anti-PEG immunoglobulin M (IgM). Further, we observed no anti-polymer IgM responses or ABC effects for hPG-grafted NPs.

Extracellular potassium concentration affects the membrane potential of neurons, and, thus, neuronal activity. Indeed, alterations of potassium levels can be related to neurological disorders, such as epilepsy and Alzheimer's disease, and, therefore, selectively detecting extracellular potassium would allow the monitoring of disease. However, currently available optical reporters are not capable of detecting small changes in potassium, in particular, in freely moving animals. Furthermore, they are susceptible to interference from sodium ions. Here, we report a highly sensitive and specific potassium nanosensor that can monitor potassium changes in the brain of freely moving mice undergoing epileptic seizures. An optical potassium indicator is embedded in mesoporous silica nanoparticles, which are shielded by an ultrathin layer of a potassium-permeable membrane, which prevents diffusion of other cations and allows the specific capturing of potassium ions. The shielded nanosensor enables the spatial mapping of potassium ion release in the hippocampus of freely moving mice.

Myeloid progenitor cells have generally been considered the predominant source of myeloid cells under steady-state conditions. Here we show that NK cells contributed to a myeloid cell lineage pool in naive and tumor-bearing mice. Using fate tracing of NKp46+ cells, we found that myeloid cells could be derived from NK cells. Notably, among mature CD11b+ CD27+ NK cells, c-Kit+ CD24+ NK cells were capable of differentiating into a range of myeloid lineages in vitro and produced neutrophils and monocytes in vivo. The differentiation was completely inhibited by NK-stimulating cytokines. In addition to the potential for differentiation into myeloid cells, c-Kit+ CD24+ NK cells retained NK cell phenotypes and effector functions. Mechanistically, GATA-2 was necessary for the differentiation of c-Kit+ CD24+ NK cells. Therefore, we discovered that GATA-2-dependent differentiation of c-Kit+ CD24+ NK cells contributes to myeloid cell development and identified a novel pathway for myeloid lineage commitment under physiological conditions.

Although poly(ethylene glycol) (PEG) is commonly used in nanoparticle design, the impact of surface topography on nanoparticle performance in biomedical applications has received little attention, despite showing significant promise in the study of inorganic nanoparticles. Control of the surface topography of polymeric nanoparticles is a formidable challenge due to the limited conformational control of linear polymers that form the nanoparticle surface. In this work, we establish a straightforward method to precisely tailor the surface topography of PEGylated polymeric nanoparticles based on tuning the architecture of shape-persistent amphiphilic bottlebrush block copolymer (BBCP) building blocks. We demonstrate that nanoparticle formation and surface topography can be controlled by systematically changing the structural parameters of BBCP architecture. Furthermore, we reveal that the surface topography of PEGylated nanoparticles significantly affects their performance. In particular, the adsorption of a model protein and the uptake into HeLa cells were closely correlated to surface roughness and BBCP terminal PEG block brush width. Overall, our work elucidates the importance of surface topography in nanoparticle research as well as provides an approach to improve the performance of PEGylated nanoparticles.

As the aging population increases, the need for new product development (NPD) for elderly-friendly food packaging is also increasing. Through the use of consumer research, this study derived the following problems when elderly people use food packaging: “The contents easily overflow when holding the container”, “It is hard to pour”, “Remnant remains after pouring”, and “It is hard to use a straw”. To address these problems, this study applied the following principles of TRIZ: principle 1 (segmentation) and principle 22 (blessing in disguise). In order to materialize the improvement plan, this study developed an elderly-friendly pouch-based packaging from the perspective of universal design. This study shows that it is possible to use the TRIZ technique in the NPD of food packaging, and that it is possible to secure commercial competitiveness from the view of universal design. This study is expected to serve as a starting point for further study on the NPD of elderly-friendly food packaging.

Since small and medium enterprises (SMEs) play an important role in economic development, the government implements various supports. Nevertheless, SMEs have difficulties in gaining a competitive advantage in the market owing to lack of capital and capacity. Accordingly, SMEs try to secure a competitive advantage through innovation. Government support is necessary for the innovation of SMEs, and it is essential for food SMEs as well. Whether government support for firms can affect firm’s innovation is still a matter of debate. In particular, it is necessary to empirically investigate the relationship between government support and innovation for SMEs in latecomers to the food industry such as Korea. Therefore, this study conducted an empirical study on the factors that determine the innovation performance of food SMEs by government support. This study used a two-stage regression model. The government support does not unilaterally affect innovation performance, but rather, an endogeneity problem occurs through the interaction between them. This study examined the interrelationships between variables for a clear estimate of government support. Before two-stage regression, this study used the ordered logistic regression to determine the instrumental variables. Each instrumental variable was estimated for the seven types of government support that are normally implemented. The result suggests that the government certification support is effective in improving the innovation performance of food SMEs. This study is useful to establish innovation strategies for supporting food SMEs’ innovation in late-coming countries.

Due to the high risk in development process, the bio-pharmaceutical industry has transformed itself into an open innovation framework in order to overcome economic risk. This study examines the relationship between outbound open innovation and financial performance in bio-pharmaceutical industry. Specifically, this study extends knowledge-based view to link the open innovation performance and licensor’s sustainability. In order to provide empirical evidence, this study uses econometric methodology with several databases including bio-pharmaceutical firms. The analysis shows firm’s desorptive capabilities have a significant effect on financial performance, confirming the application of knowledge capacity framework. The result of the study can suggest the way how the licensors can maintain the sustainability of competitiveness in bio-pharmaceutical industry.

GM-CSF as an adjuvant has been shown to promote antitumor immunity in mice and humans; however, the underlying mechanism of GM-CSF–induced antitumor immunity remains incompletely understood. In this study, we demonstrate that GM-CSF potentiates the efficacy of cancer vaccines through IL9-producing Th (Th9) cells. GM-CSF selectively enhanced Th9 cell differentiation by regulating the COX2–PGE2 pathway while inhibiting the differentiation of induced regulatory T (iTreg) cells in vitro and in vivo. GM-CSF–activated monocyte-derived dendritic cells converted tumor-specific naïve Th cells into Th9 cells, and delayed tumor growth by inducing antitumor CTLs in an IL9-dependent manner. Our findings reveal a mechanism for the adjuvanticity of GM-CSF and provide a rationale for the use of GM-CSF in cancer vaccines.

Neuropathic pain is a chronic and pathological pain caused by injury or dysfunction in the nervous system. Pro-inflammatory microglial activation with aberrant reactive oxygen species (ROS) generation in the spinal cord plays a critical role in the development of neuropathic pain. However, the efficacy of current therapeutic methods for neuropathic pain is limited because only neurons or neural circuits involved in pain transmission are targeted. Here, an effective strategy to treat pain hypersensitivity using microglia-targeting ceria-zirconia nanoparticles (CZ NPs) is reported. The CZ NPs are coated with microglia-specific antibodies to promote their delivery to microglia, and thus to improve their therapeutic efficacy. The targeted delivery facilitates the elimination of both pro-inflammatory cytokines and ROS in microglia, enabling the rapid and effective inhibition of microglial activation. As a result, greatly ameliorated mechanical allodynia is achieved in a spinal nerve transection (SNT)-induced neuropathic pain mouse model, proving the potent analgesic effect of the microglia-targeting CZ NPs. Given the generality of the approach used in this study, the microglia-targeting CZ NPs are expected to be useful for the treatment of not only neuropathic pain but also other neurological diseases associated with the vicious activation of microglia.

There is growing interest in PEGylation of cationic polymeric vehicles for gene delivery in order to improve vehicle stability and reduce toxicity, but little is known about the effects of PEG coatings on transfection. We used a polymer from the poly(amine-co-ester) (PACE) family blended with PEG-conjugated PACE at different ratios in order to explore the effects of polyplex PEGylation on the transfection efficiency of plasmid DNA, mRNA, and siRNA in vitro and mRNA in vivo. We discovered that concentrations of PACE-PEG as low as 0.25% by weight improved polyplex stability but also inhibited transfection in vitro. In vivo, the effect of PACE-PEG incorporation on mRNA transfection varied by delivery route; the addition of PACE-PEG improved local delivery to the lung, but PEGylation had little effect on intravenous systemic delivery. By both delivery routes, transfection was inhibited at concentrations higher than 5 wt% PACE-PEG. These results demonstrate that excess PEGylation can be detrimental to vehicle function, and suggest that PEGylation of cationic vehicles must be optimized by PEG content, cargo type, and delivery route.

This study examines the influence of government support, research and development (R&amp, D) investment and cooperation networks on sustainable innovation performance of the medium-sized food firms in South Korea. Climate change, population growth, lifestyle change and consumer demands for new products allow firms to explore innovation for sustainable growth. In the food industry, where various stakeholders are involved in the value chain, government support, R&amp, D investment and cooperation are affecting firms&rsquo, sustainable performance. However, there are few empirical studies that examine the relationship among them, especially regarding medium-sized food firms. This study aimed to analyze data regarding Korean food firms through a structural equation model. To overcome data scarcity, this study collected new data for 67 medium-sized food firms. The data is matched with the firms&rsquo, 10-year data on management, innovation performance, and cooperation networks. This study can contribute to filling the literature gap by exploring what innovation strategies should be used to improve food SMEs&rsquo, innovation performance in the latecomer countries, which have developed their food industries relatively recently.

This study aims to explore whether a firm&rsquo, s financial sustainability is enhanced by open innovation especially after a global financial crisis. There are few studies on the relationship between open innovation and financial sustainability. This study aimed to fill the literature gap by analyzing the change in the financial ratio according to the increase or decrease in open innovation. We used a case study method regarding large Korean food firms. Korea is a latecomer in the food industry, which is driven by large companies. This study is meaningful for financial sustainability studies of countries with a lack of resources and small market size, which require open innovation. The findings of this study are as follows: The most preferred alliance strategy of large food firms is joint research. In order to secure raw materials and markets, open innovation was actively conducted abroad, which increased growth and profitability. However, a firm which rarely adopts open innovation could grow steadily through internal strategies. On the other hand, although relatively many open innovations have been used, growth and profitability could decrease. Firms with sufficient absorptive capacity strengthen financial sustainability through open innovation.

In order to improve the health status of adolescents, studies are needed to illuminate the essence of their general and dietary lifestyle. Thus, we conducted this study to verify meaningful relationships between adolescent usage of social media (USM), which plays an important role in their life, their food consumption behavior (FCB), and their dietary satisfaction. This study used two analysis methods: t-tests and structural equation modeling (SEM). This study verified whether there was a significant difference in adolescent FCB depending on their USM using t-tests. This study proposes that the following FCBs showed significant differences between users and non-users of social media in adolescents: a tendency to try new types of food (t = 2.134, p < 0.05), a tendency to avoid foods with harmful risks such as suspected spoilage (t = 3.513, p < 0.001), a tendency to eat bread or fruit for a simple breakfast (t = −3.893, p < 0.001), and a tendency to often use home meal replacements (HMR), eat out or have food delivered (t = −3.245, p < 0.01). Furthermore, this study used SEM to verify the causal relationship between adolescent USM and their dietary satisfaction. According to the results of SEM, adolescents’ USM mediated by the FCB of preferring convenience fully mediates the negative relationship between adolescent USM and their dietary satisfaction (p < 0.01). It is necessary to reverse the situation in which adolescent dietary satisfaction decreases as their FCB of preferring convenience increases. Government regulations for food companies and autonomous efforts for quality improvements on their part are needed.

With the rapid development of information and communications technology (ICT), smart society has arrived. The emergence of smart media has changed the user&rsquo, s role. Broader communication coverage, faster Internet speeds, and an expanding application market promote user participation. Therefore, the role of users in innovation has become more important than ever. In this rapidly changing environment, it has become important for firms to consider the role of users when developing innovation strategies. It is hard for a firm to maintain all abilities and resources amid this sudden change, therefore, firms have to develop their strategy considering the user&rsquo, s role. For that reason, firms need to network with universities, researchers, firms, and users from the open innovation perspective. This study divides firm strategy into exploitation and exploration strategies in the value chain and identifies the effects of utilization strategy, exploration strategy, and the role of users in the smart media industry on firm performance.

Cell surface modification has been extensively studied to enhance the efficacy of cell therapy. Still, general accessibility and versatility are remaining challenges to meet the increasing demand for cell-based therapy. Herein, we present a facile and universal cell surface modification method that involves mild reduction of disulfide bonds in cell membrane protein to thiol groups. The reduced cells are successfully coated with biomolecules, polymers, and nanoparticles for an assortment of applications, including rapid cell assembly, in vivo cell monitoring, and localized cell-based drug delivery. No adverse effect on cellular morphology, viability, proliferation, and metabolism is observed. Furthermore, simultaneous coating with polyethylene glycol and dexamethasone-loaded nanoparticles facilitates enhanced cellular activities in mice, overcoming immune rejection.

Liquid embolic agents are considered the most promising for various embolization procedures because they enable deep penetration. For realizing effective procedures, the delivery of liquid embolic agents should be guided under X-ray imaging systems and the solidification time should be optimized for the specific indication. The biocompatibility of embolic agents is also crucial because they remain in the vessel after embolization. In this study, we synthesized new biocompatible embolic agents based on tantalum ethoxide. Tantalum alkoxide liquid embolics (TALE) possess the radiopacity for fluoroscopy and can control the penetration depth by modifying the sol-gel kinetics. Furthermore, TALE can serve as drug carriers for synergistic treatment. Using these excellent characteristics, we demonstrated that TALE agents can be used in various situations including the transarterial chemoembolization of hepatocellular carcinoma and embolotherapy of massive bleeding from the femoral artery. This article is protected by copyright. All rights reserved.

Current heterogeneous cell assembly techniques in coculture systems rely on irreversible cell layering or a cell separation membrane. However, the techniques possess major drawbacks of inefficiency in direct interactions of the assembled cell layers and cell separation following coculture, which hamper characterization and therapeutic applications of the cells following coculture. Here, we develop a reversible cell layering platform for assembly of heterogeneous cells that allows both active direct cell–cell interactions and facile cell separation. Anionic maleimide-chondroitin-sulfate is grafted onto the surface membrane of myogenic C2C12 cells and human mesenchymal stem cells (hMSCs) to modify the surface charge of the cells without cytotoxicity. A highly porous chitosan thin film is formed in situ interspacing between the heterogeneous cell layers via ionic cross-linking of cationic chitosan and anionic functionalized cells, forming compactly assembled double-layered cell constructs. The chitosan film ...

During cancer immunoediting, loss of major histocompatibility complex class I (MHC-I) in neoplasm contributes to the evasion of tumours from host immune system. Recent studies have demonstrated that most natural killer (NK) cells that are found in advanced cancers are defective, releasing the malignant MHC-I-deficient tumours from NK-cell-dependent immune control. Here, we show that a natural killer T (NKT)-cell-ligand-loaded tumour-antigen expressing antigen-presenting cell (APC)-based vaccine effectively eradicates these advanced tumours. During this process, we find that the co-expression of Tim-3 and PD-1 marks functionally exhausted NK cells in advanced tumours and that MHC-I downregulation in tumours is closely associated with the induction of NK-cell exhaustion in both tumour-bearing mice and cancer patients. Furthermore, the recovery of NK-cell function by IL-21 is critical for the anti-tumour effects of the vaccine against advanced tumours. These results reveal the process involved in the induction of NK-cell dysfunction in advanced cancers and provide a guidance for the development of strategies for cancer immunotherapy., Loss of major histocompatibility complex MHC-I expression contributes to cancer immune evasion. Here, the authors show that, in both mice and humans, MHC-I downregulation is associated with the induction of NK-cell exhaustion and that IL-21 restores NK-cell function and inhibits tumours progression.

Although treatment with the glucocorticoid-induced tumor necrosis factor receptor–related protein (GITR) agonistic antibody (DTA-1) has shown antitumor activity in various tumor models, the underlying mechanism is not fully understood. Here, we demonstrate that interleukin (IL)-21–producing follicular helper T (Tfh) cells play a crucial role in DTA-1–induced tumor inhibition. The administration of DTA-1 increased IL21 expression by Tfh cells in an antigen-specific manner, and this activation led to enhanced antitumor cytotoxic T lymphocyte (CTL) activity. Mice treated with an antibody that neutralizes the IL21 receptor exhibited decreased antitumor activity when treated with DTA-1. Tumor growth inhibition by DTA-1 was abrogated in Bcl6fl/flCd4Cre mice, which are genetically deficient in Tfh cells. IL4 was required for optimal induction of IL21-expressing Tfh cells by GITR costimulation, and c-Maf mediated this pathway. Thus, our findings identify GITR costimulation as an inducer of IL21-expressing Tfh cells and provide a mechanism for the antitumor activity of GITR agonism.

Given high business risks and interdependency with various organizations in biopharmaceutical industry, business model has become a key element for firms that aim to be more sustainable and profitable. Despite its growing importance, research on the business model design in biopharmaceutical industry is limited. In particular, there is a lack of research dealing with business models or strategies for latecomers. In the face of drastic changes such as market expansion and patent expiration, there has been growing interest in latecomer&rsquo, s business model in the biopharmaceutical industry. This study identifies different types of business model designs using hierarchical clustering. Based on an empirical study of 313 biopharmaceutical firms in Korea, we find three types of business models: business diversified research firm, non-diversified research firm, and mature firm. We then compare the general characteristics and performances of each cluster. The findings indicate that business diversification of biopharmaceutical firms is beneficial in terms of profit. This implies that the biopharmaceutical firms in latecomer countries such as Korea are recommended to consider business diversification for sustainable management.

Nanoparticles have been extensively used to deliver therapeutic drugs to tumor tissues through the extravasation of a leaky vessel via enhanced permeation and retention effect (EPR, passive targeting) or targeted interaction of tumor-specific ligands (active targeting). However, the therapeutic efficacy of drug-loaded nanoparticles is hampered by its heterogeneous distribution owing to limited penetration in tumor tissue. Inspired by the fact that cancer cells can recruit inflammatory immune cells to support their survival, we developed a click reaction-assisted immune cell targeting (CRAIT) strategy to deliver drug-loaded nanoparticles deep into the avascular regions of the tumor. Immune cell-targeting CD11b antibodies are modified with trans-cyclooctene to enable bioorthogonal click chemistry with mesoporous silica nanoparticles functionalized with tetrazines (MSNs-Tz). Sequential injection of modified antibodies and MSNs-Tz at intervals of 24 h results in targeted conjugation of the nanoparticles onto CD11b+ myeloid cells, which serve as active vectors into tumor interiors. We show that the CRAIT strategy allows the deep tumor penetration of drug-loaded nanoparticles, resulting in enhanced therapeutic efficacy in an orthotopic 4T1 breast tumor model. The CRAIT strategy does not require ex vivo manipulation of cells and can be applied to various types of cells and nanovehicles.

The financial valuation of a drug that is still under development is required for various purposes. The risk-adjusted net present value (r-NPV) method, which recently emerged in the biotech industry, uses the development attrition rate as a discount factor to reflect risk during each development phase. The r-NPV method was developed to overcome the disadvantages of the prevailing discounted cash flow and real options methods and considers drug type, as well as the stage of development in its approach. Using this method, the current study examines technology values in the biopharmaceutical industry and matches the clinical development periods and success rates of these new drugs by analyzing datasets from ClinicalTrials.gov and MedTrack DB. It thus provides support for an empirical valuation model for experts in the field. Notably, there is limited research on the attrition rate and development period of new substance drugs and the research results are not consistently presented. In addition to new substance drugs, further research is necessary to deepen understanding of the attrition rate and development period of biologically-based drugs because of their inherent physical and developmental differences. Similarly, research on performance specifics within drug class models would enable refinement of the model.

The formation of inorganic nanoparticles has been understood based on the classical crystallization theory described by a burst of nucleation, where surface energy is known to play a critical role, and a diffusion-controlled growth process. However, this nucleation and growth model may not be universally applicable to the entire nanoparticle systems because different precursors and surface ligands are used during their synthesis. Their intrinsic chemical reactivity can lead to a formation pathway that deviates from a classical nucleation and growth model. The formation of metal oxide nanoparticles is one such case because of several distinct chemical aspects during their synthesis. Typical carboxylate surface ligands, which are often employed in the synthesis of oxide nanoparticles, tend to continuously remain on the surface of the nanoparticles throughout the growth process. They can also act as an oxygen source during the growth of metal oxide nanoparticles. Carboxylates are prone to chemical reactions with different chemical species in the synthesis such as alcohol or amine. Such reactions can frequently leave reactive hydroxyl groups on the surface. Herein, we track the entire growth process of iron oxide nanoparticles synthesized from conventional iron precursors, iron-oleate complexes, with strongly chelating carboxylate moieties. Mass spectrometry studies reveal that the iron-oleate precursor is a cluster comprising a tri-iron-oxo core and carboxylate ligands rather than a mononuclear complex. A combinatorial analysis shows that the entire growth, regulated by organic reactions of chelating ligands, is continuous without a discrete nucleation step.