Pregnancy outcomes following natural conception and assisted reproduction treatment in women who received COVID-19 vaccination prior to conception: a population-based cohort study in China

IntroductionThe coronavirus disease-2019 (COVID-19) pandemic has swept across the world and continues to exert serious adverse effects on vulnerable populations, including pregnant women and neonates. The vaccines available at present were designed to prevent infection from COVID-19 strains and control viral spread. Although the incidence of pregnancy cycle outcomes are not likely to increase patients vaccinated prior to pregnancy compared with unvaccinated patients based on our knowledge of vaccination safety, there is no specific evidence to support this hypothesis. Therefore, the current study aimed to investigate the association between maternal vaccination prior to conception and pregnancy outcomes.MethodsWe retrospectively analyzed 2,614 women who received prenatal care and delivered in the Obstetrical Department of The First Affiliated Hospital of Anhui Medical University between February 2022 and November 2022. Of the 1,380 eligible pregnant women, 899 women who had received preconception vaccination were assigned to a vaccine group and 481 women who were not vaccinated were control group. Of the enrolled patients, 291 women received fertility treatment (141 vaccinated women, 150 unvaccinated women). The primary outcomes were pregnancy complications (hypothyroidism, gestational diabetes mellitus, pregnancy-induced hypertension, polyhydramnios, oligohydramnios, premature rupture of membranes and postpartum hemorrhage), obstetric outcomes (preterm birth rate, cesarean section rate) and neonatal outcomes (birth-weight, body length, low-birth-weight rate, rate of congenital defects, neonatal mortality and admission to the neonatal intensive care unit).ResultsThere was no significant difference in the incidence of complications during pregnancy and delivery when compared between the vaccine group and control group in either univariate- or multivariate-models. The type of vaccine was not associated with the odds of adverse pregnancy outcome. Among the women with infertility treatment, the vaccinated group and the unvaccinated group had similar pregnancy outcomes.ConclusionWomen who received COVID-19 vaccination prior to conception had similar maternal and neonatal outcomes as women who were unvaccinated. Our findings indicate that COVID-19 vaccinations can be safely administered prior to pregnancy in women who are planning pregnancy or assisted reproductive treatment. During new waves of COVID-19 infection, women who are planning pregnancy should be vaccinated as soon as possible to avoid subsequent infections

Nanoparticle Delivery of Immunostimulatory Agents for Cancer Immunotherapy.

Immunostimulatory agents, including adjuvants, cytokines, and monoclonal antibodies, hold great potential for the treatment of cancer. However, their direct administration often results in suboptimal pharmacokinetics, vulnerability to biodegradation, and compromised targeting. More recently, encapsulation into biocompatible nanoparticulate carriers has become an emerging strategy for improving the delivery of these immunotherapeutic agents. Such approaches can address many of the challenges facing current treatment modalities by endowing additional protection and significantly elevating the bioavailability of the encapsulated payloads. To further improve the delivery efficiency and subsequent immune responses associated with current nanoscale approaches, biomimetic modifications and materials have been employed to create delivery platforms with enhanced functionalities. By leveraging nature-inspired design principles, these biomimetic nanodelivery vehicles have the potential to alter the current clinical landscape of cancer immunotherapy

Targeted gene silencing in vivo by platelet membrane-coated metal-organic framework nanoparticles.

Small interfering RNA (siRNA) is a powerful tool for gene silencing that has been used for a wide range of biomedical applications, but there are many challenges facing its therapeutic use in vivo. Here, we report on a platelet cell membrane-coated metal-organic framework (MOF) nanodelivery platform for the targeted delivery of siRNA in vivo. The MOF core is capable of high loading yields, and its pH sensitivity enables endosomal disruption upon cellular uptake. The cell membrane coating provides a natural means of biointerfacing with disease substrates. It is shown that high silencing efficiency can be achieved in vitro against multiple target genes. Using a murine xenograft model, significant antitumor targeting and therapeutic efficacy are observed. Overall, the biomimetic nanodelivery system presented here provides an effective means of achieving gene silencing in vivo and could be used to expand the applicability of siRNA across a range of disease-relevant applications

Multimodal Enzyme Delivery and Therapy Enabled by Cell Membrane-Coated Metal–Organic Framework Nanoparticles

Therapeutic enzymes used for genetic disorders or metabolic diseases oftentimes suffer from suboptimal pharmacokinetics and stability. Nanodelivery systems have shown considerable promise for improving the performance of enzyme therapies. Here, we develop a cell membrane-camouflaged metal-organic framework (MOF) system with enhanced biocompatibility and functionality. The MOF core can efficiently encapsulate enzymes while maintaining their bioactivity. After the introduction of natural cell membrane coatings, the resulting nanoformulations can be safely administered in vivo. The surface receptors on the membrane can also provide additional functionalities that synergize with the encapsulated enzyme to target disease pathology from multiple dimensions. Employing uricase as a model enzyme, we demonstrate the utility of this approach in multiple animal disease models. The results support the use of cell membrane-coated MOFs for enzyme delivery, and this strategy could be leveraged to improve the usefulness of enzyme-based therapies for managing a wide range of important human health conditions

Coating nanoparticles with gastric epithelial cell membrane for targeted antibiotic delivery against Helicobacter pylori infection.

Inspired by the natural pathogen-host interactions and adhesion, this study reports on the development of a novel targeted nanotherapeutics for the treatment of Helicobacter pylori (H. pylori) infection. Specifically, plasma membranes of gastric epithelial cells (e.g. AGS cells) are collected and coated onto antibiotic-loaded polymeric cores, the resulting biomimetic nanoparticles (denoted AGS-NPs) bear the same surface antigens as the source AGS cells and thus have inherent adhesion to H. pylori bacteria. When incubated with H. pylori bacteria in vitro, the AGS-NPs preferentially accumulate on the bacterial surfaces. Using clarithromycin (CLR) as a model antibiotic and a mouse model of H. pylori infection, the CLR-loaded AGS-NPs demonstrate superior therapeutic efficacy as compared the free drug counterpart as well as non-targeted nanoparticle control group. Overall, this work illustrates the promise and strength of using natural host cell membranes to functionalize drug nanocarriers for targeted drug delivery to pathogens that colonize on the host cells. As host-pathogen adhesion represents a common biological event for various types of pathogenic bacteria, the bioinspired nanotherapeutic strategy reported here represents a versatile delivery platform that may be applied to treat numerous infectious diseases

A Nanomotor-Based Active Delivery System for Intracellular Oxygen Transport

Active transport of gas molecules is critical to preserve the physiological functions of organisms. Oxygen, as the most essential gas molecule, plays significant roles in maintaining the metabolism and viability of cells. Herein, we report a nanomotor-based delivery system that combines the fast propulsion of acoustically propelled gold nanowire nanomotors (AuNW) with the high oxygen carrying capacity of red blood cell membrane-cloaked perfluorocarbon nanoemulsions (RBC-PFC) for active intracellular delivery of oxygen. The oxygen delivery capacity and kinetics of the AuNW nanomotors carrying RBC-PFC (denoted as "Motor-PFC") are examined under ultrasound field. Specifically, the fast movement of the Motor-PFC under an acoustic field accelerates intracellular delivery of oxygen to J774 macrophage cells. Upon entering the cells, the oxygen loaded in the Motor-PFC is sustainably released, which maintains the cell viability when cultured under hypoxic conditions. The acoustically propelled Motor-PFC leads to significantly higher cell viability (84.4%) over a 72 h period, compared to control samples with free RBC-PFC (44.4%) or to passive Motor-PFC (32.7%). These results indicate that the Motor-PFC can act as an effective delivery vehicle for active intracellular oxygen transport. While oxygen is used here as a model gas molecule, the Motor-PFC platform can be readily expanded to the active delivery of other gas molecules to various target cells

CD4+ T cell-mimicking nanoparticles encapsulating DIABLO/SMAC mimetics broadly neutralize HIV-1 and selectively kill HIV-1-infected cells.

HIV-1 is a major global health challenge. The development of an effective vaccine and a therapeutic cure are top priorities. The creation of vaccines that focus an antibody response toward a particular epitope of a protein has shown promise, but the genetic diversity of HIV-1 stymies this progress. Therapeutic strategies that provide effective and broad-spectrum neutralization against HIV-1 infection are highly desirable. Methods: We investigated the potential of nanoengineered CD4+ T cell membrane-coated nanoparticles (TNP) encapsulating the DIABLO/SMAC mimetics LCL-161 or AT-406 (also known as SM-406 or Debio 1143) to both neutralize HIV-1 and selectively kill HIV-1-infected resting CD4+ T cells and macrophages. Results: DIABLO/SMAC mimetic-loaded TNP displayed outstanding neutralizing breadth and potency, and selectively kill HIV-1-infected cells via autophagy-dependent apoptosis while having no drug-induced off-target or cytotoxic effects on bystander cells. Genetic inhibition of early stages of autophagy abolishes this effect. Conclusion: DIABLO/SMAC mimetic loaded TNP have the potential to be used as therapeutic agents to neutralize cell-free HIV-1 and to kill specifically HIV-1-infected cells as part of an HIV-1 cure strategy

Biomimetic Nanoemulsions for Oxygen Delivery In Vivo.

Blood transfusion is oftentimes required for patients suffering from acute trauma or undergoing surgical procedures in order to help maintain the bodys oxygen levels. The continued demand worldwide for blood products is expected to put significant strain on available resources and infrastructure. Unfortunately, efforts to develop viable alternatives to human red blood cells for transfusion are generally unsuccessful. Here, a hybrid natural-synthetic nanodelivery platform that combines the biocompatibility of the natural RBC membrane with the oxygen-carrying ability of perfluorocarbons is reported. The resulting formulation can be stored long-term and exhibits a high capacity for oxygen delivery, helping to mitigate the effects of hypoxia in vitro. In an animal model of hemorrhagic shock, mice are resuscitated at an efficacy comparable to whole blood infusion. By leveraging the advantageous properties of its constituent parts, this biomimetic oxygen delivery system may have the potential to address a critical need in the clinic