Preparation, characterization, and in vitro tumor-suppressive effect of anti-miR-21-equipped RNA nanoparticles.

MicroRNAs play an irreplaceable role in gene expression regulation. Upregulation of several miRNAs increases the risk of invasion and metastasis of breast cancer cells. An oncogenic miRNA, miR-21, is highly expressed in triple-negative breast cancer (TNBC) and is associated with tumor proliferation, invasion, carcinogenesis, prognosis, and therapeutic resistance. However, targeted delivery of therapeutic anti-miRNAs into cancer cells remains challenging, especially for TNBC. In this study, we report the application of an RNA nanotechnology-based platform for the targeted delivery of anti-miR-21 by epidermal growth factor receptor (EGFR) aptamer in vitro to TNBC and chemical-resistant breast cancer cells. RNA nanoparticles reduced cell viability and sensitized breast cancer cells to doxorubicin (DOX) treatment in vitro. Inhibition of miR-21 by RNA nanoparticles suppressed TNBC cell invasion, migration, and colony formation. The results indicate the potential application of nanotechnology-based delivery platforms in clinical anti-cancer therapeutics.

Development of targeted therapy therapeutics to sensitize triple-negative breast cancer chemosensitivity utilizing bacteriophage phi29 derived packaging RNA.

BACKGROUND: To date, triple-negative breast cancer (TNBC) treatment options are limited because of the loss of target receptors and, as a result, are only managed with chemotherapy. What is worse is that TNBC is frequently developing resistance to chemotherapy. By using small interfering RNA (siRNA)-based therapeutics, our recent work demonstrated X-box-binding protein 1 (XBP1) was linked to human epidermal growth factor receptor 2 positive (HER2+) breast cancer development and chemoresistance. Given the instability, off-target effects, net negative charge, and hydrophobicity of siRNA in vivo utilization and clinical transformation, its use in treatment is hampered. Thus, the development of a siRNA-based drug delivery system (DDS) with ultra-stability and specificity is necessary to address the predicament of siRNA delivery. RESULTS: Here, we assembled RNase resistant RNA nanoparticles (NPs) based on the 3WJ structure from Phi29 DNA packaging motor. To improved targeted therapy and sensitize TNBC to chemotherapy, the RNA NPs were equipped with an epidermal growth factor receptor (EGFR) targeting aptamer and XBP1 siRNA. We found our RNA NPs could deplete XBP1 expression and suppress tumor growth after intravenous administration. Meanwhile, RNA NPs treatment could promote sensitization to chemotherapy and impede angiogenesis in vivo. CONCLUSIONS: The results further demonstrate that our RNA NPs could serve as an effective and promising platform not only for siRNA delivery but also for chemotherapy-resistant TNBC therapy.

One-Pot Generating Subunit Vaccine with High Encapsulating Efficiency and Fast Lysosome Escape for Potent Cellular Immune Response.

Utilizing nanoparticles to deliver subunit vaccine is considered to be a promising strategy to improve immune response. However, currently reported systems suffered from one or more points, for example, delicate design on molecular structures and elaborate synthesis process, low antigen and/or adjuvant encapsulation efficiency, involvement of toxic materials, and denaturing of bioactivity of antigen and/or adjuvant. To address these issues, here, for the first time, we developed a one-pot method to produce a subunit vaccine by using hexa-histidine metal assembly (HmA) to codeliver tumor-associated antigens (GP100, a peptide KTWGQYWQV) and adjuvant (CpG). The generation of subunit vaccines was detailedly characterized by various techniques, including dynamic scatter, scanning electron microscopy, transmission electron microscopy, UV-visible spectroscopy, agarose gel electrophoresis, etc. HmA displayed high efficiency on encapsulating both subunits (GP100 and CpG) under mild conditions, and the generated subunit vaccine showed a pH-dependent release profile of loaded subunits. In the cellular tests, these subunit vaccines behaved with a quick endocytosis into immune cells and a fast endo/lysosomes escape, inducing maturation of antigen presentative cells and stimulating a potent cellular immune response. These results suggested that HmA is a robust platform for fabricating subunit vaccine, with immense potential for the immunotherapy of various diseases.

Hexahistidine-Metal Assemblies: A Facile and Effective Codelivery System of Subunit Vaccines for Potent Humoral and Cellular Immune Responses.

Fully effective vaccines must induce both potent humoral and cellular immunities. Nanoparticles coencapsulating antigens and adjuvants have shown promising advantages as subunit vaccines in many aspects. However, the low loading efficiency and complicated synthesis process of these nanomaterials need to be improved. Here, we utilized hexahistidine (His6)-metal assembly (HmA) particles as carriers to codeliver ovalbumin peptides and cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs). We found that antigen/adjuvant-carrying HmA can efficiently enter into antigen-presenting cells and help the antigens escape from lysosomes to induce the maturation of these cells in vitro, characterized by increasing expression levels of costimulatory molecules and cytokines. More importantly, the vaccines with high biocompatibility can elicit strong humoral and cellular immunities by improving secretion of specific antibodies and cytokines, enhancing activation of DCs and T cells in vivo. Our results suggest that HmA provides a new approach for subunit vaccines by codelivery of antigens and adjuvants.

Phosphatase Cdc25A Negatively Regulates the Antiviral Immune Response by Inhibiting TBK1 Activity.

The phosphatase Cdc25A plays an important role in cell cycle regulation by dephosphorylating its substrates, such as cyclin-dependent kinases. In this study, we demonstrate that Cdc25A negatively regulates RIG-I-mediated antiviral signaling. We found that ectopic expression of Cdc25A in 293T cells inhibits the activation of beta interferon (IFN-ß) induced by Sendai virus and poly(I·C), while knockdown of Cdc25A enhances the transcription of IFN-ß stimulated by RNA virus infection. The inhibitory effect of Cdc25A on the antiviral immune response is mainly dependent on its phosphatase activity. Data from a luciferase assay indicated that Cdc25A can inhibit TBK1-mediated activation of IFN-ß. Further analysis indicated that Cdc25A can interact with TBK1 and reduce the phosphorylation of TBK1 at S172, which in turn decreases the phosphorylation of its downstream substrate IRF3. Consistently, knockdown of Cdc25A upregulates the phosphorylation of both TBK1-S172 and IRF3 in Sendai virus-infected or TBK1-transfected 293T cells. In addition, we confirmed that Cdc25A can directly dephosphorylate TBK1-S172-p. These results demonstrate that Cdc25A inhibits the antiviral immune response by reducing the active form of TBK1. Using herpes simplex virus 1 (HSV-1) infection, an IFN-ß reporter assay, and reverse transcription-quantitative PCR (RT-qPCR), we demonstrated that Cdc25A can also inhibit DNA virus-induced activation of IFN-ß. Using a vesicular stomatitis virus (VSV) infection assay, we confirmed that Cdc25A can repress the RIG-I-like receptor (RLR)-mediated antiviral immune response and influence the antiviral status of cells. In conclusion, we demonstrate that Cdc25A negatively regulates the antiviral immune response by inhibiting TBK1 activity.IMPORTANCE The RLR-mediated antiviral immune response is critical for host defense against RNA virus infection. However, the detailed mechanism for balancing the RLR signaling pathway in host cells is not well understood. We found that the phosphatase Cdc25A negatively regulates the RNA virus-induced innate immune response. Our studies indicate that Cdc25A inhibits the RLR signaling pathway via its phosphatase activity. We demonstrated that Cdc25A reduces TBK1 activity and consequently restrains the activation of IFN-ß transcription as well as the antiviral status of nearby cells. We showed that Cdc25A can also inhibit DNA virus-induced activation of IFN-ß. Taken together, our findings uncover a novel function and mechanism for Cdc25A in regulating antiviral immune signaling. These findings reveal Cdc25A as an important negative regulator of antiviral immunity and demonstrate its role in maintaining host cell homeostasis following viral infection.

Shape Effect of Nanoparticles on Tumor Penetration in Monolayers Versus Spheroids.

The physical properties of nanoparticles (NPs), such as size, surface chemistry, elasticity, and shape, have exerted a profound influence on tumor penetration. However, the effect of shape on cellular uptake and tumor penetration is still unclear because of the different chemical compositions and shapes of tested particles and the use of inapposite cellular models. To discover the effect of NP shapes on cellular uptake and tumor penetration and bridge the gap between models in vivo and in vitro, elongated polystyrene (PS) NPs with a fixed volume, an identical chemical composition, and the same zeta potential, but with different aspect ratios (ARs), were generated. The physical properties, cellular uptake, tumor penetration, and corresponding mechanisms of these NPs were thoroughly investigated. We discovered that the elongated PS particles with higher ARs had lower uptake rates in the 2-dimensional cell monolayer culture model in vitro, but they showed optimal ARs in the evaluated three-dimensional spheroid model. Although the elongated PS particles had a similar tumor penetration mechanism (mainly through extracellular pathways), the percentage of penetration using these mechanisms was strongly dependent on the ARs. As an alternative model for studies in vivo, spheroids were used instead of the cell monolayer for the development of drug delivery systems. In addition, the physicochemical properties of NPs must be delicately balanced and adjusted to achieve the best therapeutic outcomes.

MicroRNA-33a disturbs influenza A virus replication by targeting ARCN1 and inhibiting viral ribonucleoprotein activity.

In order to explore the roles of microRNA(s) [miRNA(s)] in the influenza A virus life cycle, we compared the miRNA profiles of 293T and HeLa cell lines, as influenza A virus can replicate efficiently in 293T cells but only poorly in HeLa cells. We analysed differentially expressed miRNAs and identified five, including miR-33a, that could disturb influenza A virus replication significantly. Using TargetScan analysis, we found that ARCN1 could be a potential target of miR-33a. To confirm whether miR-33a could truly target ARCN1, we generated a luciferase reporter for the ARCN1 3' untranslated region (UTR) and performed a luciferase assay. The data indicated that miR-33a could suppress the luciferase activity of the reporter for the ARCN1 3' UTR but not a reporter in which the predicted miR-33a targeting sites on ARCN1 3' UTR were mutated. We performed immunoblotting to confirm that miR-33a could downregulate the protein level of ARCN1. Consistently, the level of ARCN1 protein in HeLa cells was significantly lower than that in 293T cells. We also demonstrated that ectopic expression of ARCN1 could partially rescue the inhibitory effect of miR-33a on virus replication. Furthermore, we demonstrated that miR-33a could impede virus replication at the stage of virus internalization, which was similar to the pattern for knockdown of ARCN1, indicating that miR-33a inhibits influenza virus infection by suppressing ARCN1 expression. In addition, we found that miR-33a could also weaken the viral ribonucleoprotein activity in an ARCN1-independent manner. In conclusion, we found that miR-33a is a novel inhibitory factor for influenza A virus replication.

Mulched Drip Fertigation with Growth Inhibitors Reduces Bundle-Sheath Cell Leakage and Improves Photosynthesis Capacity and Barley Production in Semi-Arid Regions.

A better understanding of the factors that reduce bundle-sheath cell leakage to CO2 (Փ), enhance 13C carbon isotope discrimination, and enhance the photosynthetic capacity of barley leaves will be useful to develop a nutrient- and water-saving strategy for dry-land farming systems. Therefore, barley plants were exposed to a novel nitrification inhibitor (NI) (3,4-dimethyl-1H-pyrazol-1-yl succinic acid) (DMPSA) and a urease inhibitor (UI) (N-butyl thiophosphorictriamide (NBPT)) with mulched drip fertigation treatments, which included HF (high-drip fertigation (370 mm) under a ridge furrow system), MF (75% of HF, moderate-drip fertigation under a ridge furrow system), LF (50% of HF, low-drip fertigation under a ridge furrow system), and TP (traditional planting with no inhibitors or drip fertigation strategies). The results indicated that the nitrification inhibitor combined with mulched drip fertigation significantly reduced bundle-sheath cell leakage to CO2 (Փ) as a result of increased soil water content; this was demonstrated by the light and CO2 response curves of the photosynthesis capacity (An), the apparent quantum efficiency (α), and the 13C-photosynthate distribution. In the inhibitor-based strategy, the use of the urease and nitrification inhibitors reduced Փ by 35% and 39% compared with TP. In the NI-HF strategy, it was found that barley could retain the maximum photosynthesis capacity by increasing the leaf area index (LAI), An, rubisco content, soluble protein, dry matter per plant, and productivity. The CO2 and light response curves were considerably improved in the NI-HF and NI-MF treatments due to a higher 13C carbon isotope (Δ‱), respiration rate (Rd), and Ci/Ca, therefore obtaining the minimum Փ value. With both inhibitors, there was a significant difference between HF and LF drip fertigation. The NI-MF treatment significantly increased the grain yield, total chlorophyll content, WUE, and NUE by 52%, 47%, 57%, and 45%, respectively. Collectively, the results suggest that the new nitrification inhibitor (DMPSA) with HF or MF mulched drip fertigation could be promoted in semi-arid regions in order to mitigate bundle-sheath cell leakage to CO2 (Փ), without negatively affecting barley production and leading to the nutrient and water use efficiency of barley.

Circular RNAs in vascular diseases.

Vascular diseases are the leading cause of morbidity and mortality worldwide and are urgently in need of diagnostic biomarkers and therapeutic strategies. Circular RNAs (circRNAs) represent a unique class of RNAs characterized by a circular loop configuration and have recently been identified to possess a wide variety of biological functions. CircRNAs exhibit exceptional stability, tissue specificity, and are detectable in body fluids, thus holding promise as potential biomarkers. Their encoding function and stable gene expression also position circRNAs as an excellent alternative to gene therapy. Here, we briefly review the biogenesis, degradation, and functions of circRNAs. We summarize circRNAs discovered in major vascular diseases such as atherosclerosis and aneurysms, with a particular focus on molecular mechanisms of circRNAs identified in vascular endothelial cells and smooth muscle cells, in the hope to reveal new directions for mechanism, prognosis and therapeutic targets of vascular diseases.

One-step electrodeposition preparation of boron nitride and samarium co-modified Ti/PbO2 anode with ultra-long lifetime: highly efficient degradation of lincomycin wastewater.

Lincomycin (LC) is an extensively applied broad-spectrum antibiotic, and its considerable residues in wastewater have caused a series of environmental problems, which makes degradation of LC wastewater extremely urgent. In this work, we have constructed a novel boron nitride (BN) and samarium (Sm) co-modified Ti/PbO2 as anode for high-performance degradation of LC wastewater. Compared with Ti/PbO2, Ti/PbO2-Sm, and Ti/PbO2-BN electrodes, Ti/PbO2-BN-Sm electrode with smaller pyramidal particles possesses higher oxygen evolution potential (2.32 V), excellent accelerated service life (103 h), and outstanding electrocatalytic activity. The single-factor experiments demonstrate that under optimized conditions (current density of 20 mA.cm-2, 6.0 g L-1 Na2SO4, pH 9, and temperature of 30°C), removal rate and COD degradation rate of LC at 3 h have reached 92.85% and 89.11%, respectively. At the same time, degradation of LC is in accordance with the primary kinetic model. Based on the analysis of high-performance liquid chromatography-mass spectrometry (HPLC-MS), four possible degradation pathways are hypothesized. Therefore, efficient electrochemical degradation of LC by using an extremely long-life Ti/PbO2 electrode with high catalytic activity may be a promising method.

MicroRNA-200 Loaded Lipid Nanoparticles Promote Intestinal Epithelium Regeneration in Canonical MicroRNA-Deficient Mice.

Intestinal epithelium undergoes regeneration after injuries, and the disruption of this process can lead to inflammatory bowel disease and tumorigenesis. Intestinal stem cells (ISCs) residing in the crypts are crucial for maintaining the intestinal epithelium's homeostasis and promoting regeneration upon injury. However, the precise role of DGCR8, a critical component in microRNA (miRNA) biogenesis, in intestinal regeneration remains poorly understood. In this study, we provide compelling evidence demonstrating the indispensable role of epithelial miRNAs in the regeneration of the intestine in mice subjected to 5-FU or irradiation-induced injury. Through a comprehensive pooled screen of miRNA function in Dgcr8-deficient organoids, we observe that the loss of the miR-200 family leads to the hyperactivation of the p53 pathway, thereby reducing ISCs and impairing epithelial regeneration. Notably, downregulation of the miR-200 family and hyperactivation of the p53 pathway are verified in colonic tissues from patients with active ulcerative colitis (UC). Most importantly, the transient supply of miR-200 through the oral delivery of lipid nanoparticles (LNPs) carrying miR-200 restores ISCs and promotes intestinal regeneration in mice following acute injury. Our study implies the miR-200/p53 pathway as a promising therapeutic target for active UC patients with diminished levels of the miR-200 family. Furthermore, our findings suggest that the clinical application of LNP-miRNAs could enhance the efficacy, safety, and acceptability of existing therapeutic modalities for intestinal diseases.

GE11-antigen-loaded hepatitis B virus core antigen virus-like particles efficiently bind to TNBC tumor.

Purpose: This study aimed to explore the possibility of utilizing hepatitis B core protein (HBc) virus-like particles (VLPs) encapsulate doxorubicin (Dox) to reduce the adverse effect caused by its off-target and toxic side effect. Methods: Here, a triple-negative breast cancer (TNBC) tumor-targeting GE11-HBc VLP was constructed through genetic engineering. The GE11 peptide, a 12-amino-acid peptide targeting epidermal growth factor receptor (EGFR), was inserted into the surface protein loops of VLPs. The Dox was loaded into HBc VLPs by a thermal-triggered encapsulation strategy. The in vitro release, cytotoxicity, and cellular uptake of TNBC tumor-targeting GE11-HBc VLPs was then evaluated. Results: These VLPs possessed excellent stability, DOX loading efficiency, and preferentially released drug payload at high GSH levels. The insertion of GE11 targeting peptide caused improved cellular uptake and enhanced cell viability inhibitory in EGFR high-expressed TNBC cells. Conclusion: Together, these results highlight DOX-loaded, EGFR-targeted VLPs as a potentially useful therapeutic choice for EGFR-overexpressing TNBC.

High-efficient removal of U(VI) from aqueous solution by self-assembly pomelo peel/palygorskite composite.

The efficient separation of low-concentration radionuclides by the eco-friendly adsorbent is a compelling requirement in the development of nuclear industry. Hence, a novel composite consisted of one-dimensional palygorskite (Pal) and three-dimensional pomelo peel (PP) is prepared by self-assembly approach (PP/Pal) and coupling agent approach (PP/KPal) for removing uranium (U(VI)) from aqueous solution. Moreover, the mass ratio (PP/Pal), adsorbent dosage, pH, contact time, temperature, and ionic strength are investigated. Two adsorption kinetic models and isotherm models are used to investigate the kinetic behaviors and adsorption capacity, respectively. The maximum adsorption capacities were 370.5 mg·g-1 on PP/Pal and 357.3 mg·g-1 on PP/KPal at pH 6.0, contact time 150 min and 25 °C. Meanwhile, the composite can be easily separated from water via a simple filtering. Furthermore, thermodynamic parameters indicate that adsorption is an endothermic and spontaneous process. And the surface complexation, ion exchange, and electrostatic attraction play a vital role. This work shows that the PP/Pal composite with high efficiency, low cost, and green has a further application in the treatment of wastewater containing U(VI).

Lactic dehydrogenase-lymphocyte ratio for predicting prognosis of severe COVID-19.

ABSTRACT: To develop a useful score for predicting the prognosis of severe corona virus disease 2019 (COVID-19) patients.We retrospectively analyzed patients with severe COVID-19 who were admitted from February 10, 2020 to April 5, 2020. First, all patients were randomly assigned to a training cohort or a validation cohort. By univariate analysis of the training cohort, we developed combination scores and screened the superior score for predicting the prognosis. Subsequently, we identified the independent factors influencing prognosis. Finally, we demonstrated the predictive efficiency of the score in validation cohort.A total of 145 patients were enrolled. In the training cohort, nonsurvivors had higher levels of lactic dehydrogenase than survivors. Among the 7 combination scores that were developed, lactic dehydrogenase-lymphocyte ratio (LLR) had the highest area under the curve (AUC) value for predicting prognosis, and it was associated with the incidence of liver injury, renal injury, and higher disseminated intravascular coagulation (DIC) score on admission. Univariate logistic regression analysis revealed that C-reactive protein, DIC score ≥2 and LLR >345 were the factors associated with prognosis. Multivariate analysis showed that only LLR >345 was an independent risk factor for prognosis (odds ratio [OR] = 9.176, 95% confidence interval [CI]: 2.674-31.487, P < .001). Lastly, we confirmed that LLR was also an independent risk factor for prognosis in severe COVID-19 patients in the validation cohort where the AUC was 0.857 (95% CI: 0.718-0.997).LLR is an accurate predictive score for poor prognosis of severe COVID-19 patients.

Preparation of graphene oxide-modified palygorskite nanocomposites for high-efficient removal of Co(II) from wastewater.

Removing Co(II) from wastewater is urgent due to the threat to the environment and human health. In the work, the nanocomposite of graphene oxide-modified palygorskite (mPal-GO) is synthesized by cross-linking one-dimensional palygorskite (Pal) with two-dimensional material graphene oxide (GO), and used to remove Co(II) from wastewater. Its structure is characterized by Fourier transformed infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and Brunauer-Emmett-Teller (BET) surface area measurement. The parameters, such as mass ratio (GO:mPal), temperature, pH, and contact time, are carefully investigated. The results indicate that pseudo-second-order equation and Langmuir isotherm model are the best fitting one in the adsorption process of Co(II) onto mPal-GO. The maximum adsorption capacity achieves 16.9 mg/g at pH = 6.0 and T = 298 K according to the Langmuir model analysis. Furthermore, mPal-GO can be reused more than 5 times with a slight decrease according to the adsorption-desorption cycle experiments. Finally, mPal-GO with the low-cost and easy separation is a promising candidate for removing of Co(II) from wastewater.

A Strategy to Fight against Triple-Negative Breast Cancer: pH-Responsive Hexahistidine-Metal Assemblies with High-Payload Drugs.

Triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer, is difficult to be targeted therapeutically due to negative expression of the bioreceptor, which leads to the poorest overall four-year survival rate among all cancer subtypes. We proposed that the nanomedicine featuring high payload and pH-responsive release of the loaded drugs could assist the TNBC treatment. In the present study, the His6-metal assemblies (HmA) were employed to encapsulate the doxorubicin (Dox), and the effect of HmA loaded with Dox (HmA@Dox) on treating TNBC was evaluated in vitro and in vivo. We found that the participation of Dox in the formation of HmA leads to high loading efficiency (99.4% for concentration ≤ 1 mg/mL) and the loading capacity (50.7% for concentration ≥ 10 mg/mL) of Dox encapsulated into HmA. HmA@Dox exhibited a narrow size distribution on the nanoscale, a pH-responsive release of loaded Dox, a quick endocytosis process, and fast lysosome escape. Most importantly, the HmA@Dox showed high efficacy in killing various breast cancer cells (MCF-7, MDA-MB-231, and MDA-MB-453) in vitro and depressing the development of TNBC in vivo. Our results demonstrated that such a strategy for designing a nanomedicine with high payload and responsive release of drugs to the environment around the tumor was of great importance to treat TNBC.

Systemic Delivery of Aptamer-Conjugated XBP1 siRNA Nanoparticles for Efficient Suppression of HER2+ Breast Cancer.

siRNA therapeutics as an emerging class of drug development is successfully coming to clinical utilization. The RNA-based therapy is widely utilized to explore the mechanism and cure a variety of gene-specific diseases. Tumor is an oncogene-driven disease; many genes are related to tumor progression and chemoresistance. Although human epidermal growth factor receptor 2 (HER2)-targeted monoclonal antibody therapy has dramatically improved the survival rate, chemotherapy remains essential to HER2-positive (HER2+) breast cancer patients. Recently, X-box binding protein 1 (XBP1) has been involved in triple-negative breast cancer (TNBC) chemoresistance and progression, but its function in HER2+ breast cancer is poorly explored. Here, we silenced XBP1 expression using RNase-resistant RNA nanoparticles (NPs). Intravenous injection of RNA NPs with HER2-specific aptamers resulted in strong binding to tumors but not to healthy tissues. XBP1 deletion by RNA NPs impaired angiogenesis and inhibited cell proliferation, significantly suppressed breast cancer growth, and promoted the sensitization of chemotherapy in an HER2+ breast cancer mouse model. Overall, these results reveal the function of XBP1 in HER2+ breast cancer development and chemoresistance and imply that targeting XBP1 by RNA NPs may offer an easy and promising strategy for a combination treatment of breast cancer in the future.

A Facile and Universal Method to Efficiently Fabricate Diverse Protein Capsules for Multiple Potential Applications.

Proteins are considered to be one of the most important highly reproducible and monodisperse building blocks with specific functions in life sciences and material science. Protein capsules and their hybrids composed of protein-polymer conjugates have been intensively explored in drug delivery, catalysis, and cell-mimicking functions. Herein, we present a facile, universal, and efficient method to fabricate the diverse protein capsules, independent of the molecular weight (Mw), isoelectric points (IEP), wettability, amino acid sequence, and functional domains of enumerated proteins. The protein capsules were well characterized by various techniques. Furthermore, their ability to store the original protein functionality was demonstrated, which was mainly embodied in their enzyme responsiveness and good biocompatibility in vitro and in vivo. We believe that these protein capsules have multiple potential applications such as in drug delivery, tissue engineering, catalysis, and other application fields.

Hexahistidine-metal assemblies: A promising drug delivery system.

It is of considerable interest to construct an ideal drug delivery system (i.e., high drug payload, minimal cytotoxicity, rapid endocytosis, and lysosomal escape) under mild conditions for disease treatment, tissue engineering, bioimaging, etc. Inspired by the coordinative interactions between histidine and metal ions, we present the facile synthesis of hexahistidine (His6)-metal assembly (HmA) particles under mild conditions for the first time. The HmA particles presented a high loading capacity, a wide variety of loadable drugs, minimal cytotoxicity, quick internalization, the ability to bypass the lysosomes, and rapid intracellular drug release. In addition, HmA encapsulation largely improved the antitumor ability of camptothecin (CPT) relative to free CPT. By capitalizing on these promising features in drug delivery, HmA will have great potential in various biomedical fields. STATEMENT OF SIGNIFICANCE: It is of considerable interest to construct an ideal drug delivery system (i.e., high drug payload, minimal cytotoxicity, rapid endocytosis, and lysosomal escape) under mild conditions. Inspired by the coordinative interactions between histidine and metal ions, we present for the first time the facile synthesis of Hexahistidine (His6)-metal assembly (HmA) particles under mild conditions. The HmA particles exhibited a high loading capacity, a wide variety of loadable drugs, minimal cytotoxicity, quick internalization, the ability to bypass the lysosomes, and rapid intracellular drug release. By capitalizing on these promising features in drug delivery, HmA will have great potential in various biomedical fields.

Designing nanoparticles with improved tumor penetration: surface properties from the molecular architecture viewpoint.

Cancer is the second most common cause of death, and nanomedicine is regarded as one of the strategies that may revolutionize cancer treatments. However, the tumor microenvironment (e.g., increased interstitial fluid pressure and dense extracellular matrix) hinders the penetration of nanomedicine into tumor cells, which leads to a short acting time and low drug concentration with tumors, eventually leading to a high recurrence rate and therapeutic failure in clinics. Developing a delivery system with deep penetration ability into the tumor has always been pursued and highly desirable for cancer treatments. Inspired by the high cellular uptake efficiency of enveloped viruses with rough and nanoscale surfaces, we constructed polystyrene nanoparticles (NPs) with similar sizes and charges, but with different surface topologies at the molecular level, by conjugating poly(propylene imine) (PPI) dendrimers with different generations onto the NPs. We found that subtle changes made to the surficial chemical properties led to changes in surface roughness and wettability, which considerably influenced the cellular internalization, endocytosis mechanism, and penetration into the tumor model both in vitro and in vivo. This will shed light on the future design of drug delivery vehicles and facilitate understanding the interactions between NP surfaces and cells, as well as tumor penetration.