Lipid-based nanoparticles (LBNPs) are biocompatible and biodegradable vesicles that are considered to be one of the most efficient drug delivery platforms. Due to the prominent advantages, such as long circulation time, slow drug release, reduced toxicity, high transfection efficiency, and endosomal escape capacity, such synthetic nanoparticles have been widely used for carrying genetic therapeutics, particularly nucleic acids that can be applied in the treatment for various diseases, including congenital diseases, cancers, virus infections, and chronic inflammations. Despite great merits and multiple successful applications, many extracellular and intracellular barriers remain and greatly impair delivery efficacy and therapeutic outcomes. As such, the current state of knowledge and pitfalls regarding the gene delivery and construction of LBNPs will be initially summarized. In order to develop a new generation of LBNPs for improved delivery profiles and therapeutic effects, the modification strategies of LBNPs will be reviewed. On the basis of these developed modifications, the performance of LBNPs as therapeutic nanoplatforms have been greatly improved and extensively applied in immunotherapies, including infectious diseases and cancers. However, the therapeutic applications of LBNPs systems are still limited due to the undesirable endosomal escape, potential aggregation, and the inefficient encapsulation of therapeutics. Herein, we will review and discuss recent advances and remaining challenges in the development of LBNPs for nucleic acid-based immunotherapy.

Poly(glycerol sebacate) (PGS), a biodegradable elastomer, has been extensively explored in biomedical applications for its favorable mechanical properties and biocompatibility. Efforts have been made to fabricate multifunctional PGS copolymer in recent years, in particular PGS-co-PEG (poly(glycerol sebacate)-co-polyethylene glycol) polymers. However, rare research has been systematically conducted on the effect of reactant ratios on physicochemical properties and biocompatibility of PGS copolymer till now. In this study, a serial of PEGylated PGS (PEGS) with PEG content from 20% to 40% and carboxyl to hydroxyl from 0.67 to 2 were synthesized by thermal curing process. The effects of various PEGS on the mechanical strength and biological activity were further compared and optimized. The results showed that the PEGS elastomers around 20PEGS-1.0C/H and 40PEGS-1.5C/H exhibited the desirable hydrophilicity, degradation behaviors, mechanical properties and cell viability. Subsequently, the potential applications of the 20PEGS-1.0C/H and 40PEGS-1.5C/H in bone repair scaffold and vascular reconstruction were investigated and the results showed that 20PEGS-1.0C/H and 40PEGS-1.5C/H could significantly improve the mechanical strength for the calcium phosphate scaffolds and exhibited preferable molding capability for fabrication of the vascular substitute. These results confirmed that the optimized PEGS elastomers should be promising multifunctional substrates in biomedical applications.

The vast majority of cancers are treatable when diagnosed early. However, due to the elusive trace and the limitation of traditional biopsies, most cancers have already spread widely and are at advanced stages when they are first diagnosed, causing ever-increasing mortality in the past decades. Hence, developing reliable methods for early detection and diagnosis of cancer is indispensable. Recently, extracellular vesicles (EVs), as circulating phospholipid vesicles secreted by cells, are found to play significant roles in the intercellular communication as well as the setup of tumor microenvironments and have been identified as one of the key factors in the next-generation technique for cancer diagnosis. However, EVs present in complex biofluids that contain various contaminations such as nonvesicle proteins and nonspecific EVs, resulting in the interference of screening for desired biomarkers. Therefore, applicable isolation and enrichment methods that guarantee scale-up of sample volume, purity, speed, yield, and tumor specificity are necessary. In this review, we introduce current technologies for EV separation and summarize biomarkers toward EV-based cancer liquid biopsy. In conclusion, a novel systematic isolation method that guarantees high purity, recovery rate, and tumor specificity is still missing. Besides that, a dual-model EV-based clinical trial system includes isolation and detection is a hot trend in the future due to efficient point-of-care needs. In addition, cancer-related biomarkers discovery and biomarker database establishment are essential objectives in the research field for diagnostic settings.

Injectable hydrogels have been widely applied in the field of regenerative medicine. However, current techniques for injectable hydrogels are facing a challenge when trying to generate a biomimetic, porous architecture that is well-acknowledged to facilitate cell behaviors. In this study, an injectable, interconnected, porous hyaluronic acid (HA) hydrogel based on an in-situ bubble self-generation and entrapment process was developed. Through an amide reaction between HA and cystamine dihydrochloride activated by EDC/NHS, CO₂ bubbles were generated and were subsequently entrapped inside the substrate due to a rapid gelation-induced retention effect. HA hydrogels with different molecular weights and concentrations were prepared and the effects of the hydrogel precursor solution’s concentration and viscosity on the properties of hydrogels were investigated. The results showed that HA10-10 (10 wt.%, MW 100,000 Da) and HA20-2.5 (2.5 wt.%, MW 200,000 Da) exhibited desirable gelation and obvious porous structure. Moreover, HA10-10 represented a high elastic modulus (32 kPa). According to the further in vitro and in vivo studies, all the hydrogels prepared in this study show favorable biocompatibility for desirable cell behaviors and mild host response. Overall, such an in-situ hydrogel with a self-forming bubble and entrapment strategy is believed to provide a robust and versatile platform to engineer injectable hydrogels for a variety of applications in tissue engineering, regenerative medicine, and personalized therapeutics.

Cardiovascular diseases (CVD) are the leading cause of death and morbidity in the world and are a major contributor to healthcare costs. Although enormous progress has been made in diagnosing CVD, there is an urgent need for more efficient early detection and the development of novel diagnostic tools. Currently, CVD diagnosis relies primarily on clinical symptoms based on molecular imaging (MOI) or biomarkers associated with CVDs. However, sensitivity, specificity, and accuracy of the assay are still challenging for early-stage CVDs. Nanomaterial platform has been identified as a promising candidate for improving the practical usage of diagnostic tools because of their unique physicochemical properties. In this review article, we introduced cardiac biomarkers and imaging techniques that are currently used for CVD diagnosis. We presented the applications of various nanotechnologies on diagnosis within cardiac immunoassays (CIAs) and molecular imaging. We also summarized and compared different cardiac immunoassays based on their sensitivities and working ranges of biomarkers.