Impact of the conjugation of antibodies to the surfaces of polymer nanoparticles on the immune cell targeting abilities

Antibodies have been widely used to provide targeting ability and to enhance bioactivity owing to their high specificity, availability, and diversity. Recent advances in biotechnology and nanotechnology permit site-specific engineering of antibodies and their conjugation to the surfaces of nanoparticles (NPs) in various orientations through chemical conjugations and physical adhesions. This study proposes the conjugation of poly(lactic-co-glycolic acid) (PLGA) NPs with antibodies by using two distinct methods, followed by a comparison between the cell-targeting efficiencies of both techniques. Full-length antibodies were conjugated to the PLGA-poly(ethylene glycol)-carboxylic acid (PLGA-PEG-COOH) NPs through the conventional carbodiimide coupling reaction, and f(ab′)2 antibody fragments were conjugated to the PLGA-poly(ethylene glycol)-maleimide(PLGA-PEG-Mal) NPs through interactions between the f(ab′)2 fragment thiol groups and the maleimide located on the nanoparticle surface. The results demonstrate that the PLGA nanoparticles conjugated with the f(ab′)2 antibody fragments had a higher targeting efficiency in vitro and in vivo than that of the PLGA nanoparticles conjugated with the full-length antibodies. The results of this study can be built upon to design a delivery technique for drugs through biocompatible nanoparticles.This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIT) (NRF-2019R1A4A1028700 and NRF-2019R1C1C1006300). This work was supported by the Fourth Stage of Brain Korea 21 Project of the Department of Intelligent Precision Healthcare and IBS-R015-D1

Extracellular vesicle encapsulated nicotinamide delivered via a trans-scleral route provides retinal ganglion cell neuroprotection

The progressive and irreversible degeneration of retinal ganglion cells (RGCs) and their axons is the major characteristic of glaucoma, a leading cause of irreversible blindness worldwide. Nicotinamide adenine dinucleotide (NAD) is a cofactor and metabolite of redox reaction critical for neuronal survival. Supplementation with nicotinamide (NAM), a precursor of NAD, can confer neuroprotective effects against glaucomatous damage caused by an age-related decline of NAD or mitochondrial dysfunction, reflecting the high metabolic activity of RGCs. However, oral supplementation of drug is relatively less efficient in terms of transmissibility to RGCs compared to direct delivery methods such as intraocular injection or delivery using subconjunctival depots. Neither method is ideal, given the risks of infection and subconjunctival scarring without novel techniques. By contrast, extracellular vesicles (EVs) have advantages as a drug delivery system with low immunogeneity and tissue interactions. We have evaluated the EV delivery of NAM as an RGC protective agent using a quantitative assessment of dendritic integrity using DiOlistics, which is confirmed to be a more sensitive measure of neuronal health in our mouse glaucoma model than the evaluation of somatic loss via the immunostaining method. NAM or NAM-loaded EVs showed a significant neuroprotective effect in the mouse retinal explant model. Furthermore, NAM-loaded EVs can penetrate the sclera once deployed in the subconjunctival space. These results confirm the feasibility of using subconjunctival injection of EVs to deliver NAM to intraocular targets

Short Review on Advances in Hydrogel-Based Drug Delivery Strategies for Cancer Immunotherapy

© 2021, The Korean Tissue Engineering and Regenerative Medicine Society.Cancer immunotherapy has become the new paradigm of cancer treatment. The introduction and discovery of various therapeutic agents have also accelerated the application of immunotherapy in clinical trials. However, despite the significant potency and demonstrated advantages of cancer immunotherapy, its clinical application to patients faces several safety and efficacy issues, including autoimmune reactions, cytokine release syndrome, and vascular leak syndrome-related issues. In addressing these problems, biomaterials traditionally used for tissue engineering and drug delivery are attracting attention. Among them, hydrogels can be easily injected into tumors with drugs, and they can minimize side effects by retaining immune therapeutics at the tumor site for a long time. This article reviews the status of functional hydrogels for effective cancer immunotherapy. First, we describe the basic mechanisms of cancer immunotherapy and the advantages of using hydrogels to apply these mechanisms. Next, we summarize recent advances in the development of functional hydrogels designed to locally release various immunotherapeutic agents, including cytokines, cancer immune vaccines, immune checkpoint inhibitors, and chimeric antigen receptor-T cells. Finally, we briefly discuss the current problems and possible prospects of hydrogels for effective cancer immunotherapy.11Nsciescopuskc

Mucoadhesive and antifouling Janus polysaccharide film for prevention of colorectal cancer recurrence post‐surgery

Abstract Colorectal cancer is one of the most common cancers, and current treatment options include surgery, chemotherapy, and radiation therapy. Most patients undergo surgery, which often requires extensive resection of the colon to prevent recurrence and metastasis of residual malignant tumor cells, leading to postoperative pain and discomfort in daily routines. Although versatile therapeutic patches have been developed to induce tumor apoptosis, achieving both great adhesiveness on the mucus layers of the colon tissue and anti‐cell/tissue adhesion to other surrounding organs remains a challenge. Herein, we report a Janus polysaccharide film comprising two polymers: mussel‐inspired catechol‐conjugated chitosan (Chi‐C) with muco‐adhesiveness, and alginate (Alg) with anti‐adhesion property. The Chi‐C and Alg polymers form a stably entangled bilayer film via electrostatic interactions. The Janus film shows a strong tissue adhesive strength of ∼10 kPa for the Chi‐C layer and weak strength of ∼1 kPa for the Alg layer. Particularly, the Janus film encapsulating an anti‐cancer drug exhibits a directional release profile to the tumor site, which is effective for triggering tumor death in in vivo colorectal tumor resection model. Ultimately, such anti‐cancer material strategies using bilayered structures are promising for advanced tumor therapy

Sepsis diagnosis and treatment using nanomaterials

Sepsis is a life-threatening reaction that occurs when the body's severe response to an infection damages the host's own tissues. Sepsis has been globally recognized as a fatal disease. Rapid treatment of sepsis requires prompt identification, administering antibiotics, careful hemodynamic support, and treating the cause of the infection. Clinical outcomes of sepsis depend on early diagnosis and appropriate treatment. Unfortunately, current sepsis diagnosis and treatment, such as polymerase chain reaction-based assay, blood culture assay, and antibiotic therapy, are ineffective; consequently, sepsis-related mortality remains high and increases antimicrobial resistance. To overcome this challenge, nanotechnology, which involves engineering at a nanoscale, is used for diagnosing and treating sepsis. Preclinical models have shown protective effects and potential utility in managing septic shock. Furthermore, nanotechnology treatments based on diverse materials result in the effective treatment of sepsis, improving the survival rate. In this review, we present an overview of the recent research advancements in nanotechnology to diagnose and treat sepsis with a brief introduction to sepsis.11Nsciescopuskc

Biofunctional Layered Double Hydroxide Nanohybrids for Cancer Therapy

© 2022 by the authors.Layered double hydroxides (LDHs) with two-dimensional nanostructure are inorganic materials that have attractive advantages such as biocompatibility, facile preparation, and high drug loading capacity for therapeutic bioapplications. Since the intercalation chemistry of DNA molecules into the LDH materials were reported, various LDH nanohybrids have been developed for biomedical drug delivery system. For these reasons, LDHs hybridized with numerous therapeutic agents have a significant role in cancer imaging and therapy with targeting functions. In this review, we summarized the recent advances in the preparation of LDH nanohybrids for cancer therapeutic strategies including gene therapy, chemotherapy, immunotherapy, and combination therapy.11Nsciescopu

Biomaterial-based strategies to prime dendritic cell-mediated anti-cancer immune responses

Cancer immunotherapy has been extremely successful in curing patients over the last decade. Immune checkpoint blockades (ICBs) that unleash the brakes in T-cells to promote cytotoxicity against cancer cells are the most successful forms of cancer immunotherapy, yet therapeutic efficacy needs to be improved as only a fraction of patients responds. Dendritic cells (DCs) are immune cells that prime immune responses by collecting information in tumour tissues, and carrying that information to T-cells, thus delivering proper information to DCs is essential. Biomaterial-based approaches can be powerful tools for this purpose, as biomaterials allow us to deliver a variety of immunotherapeutic agents at the right time and place. Herein, we review the key concepts of cancer immunotherapy; discuss the principles for designing biomaterials to deliver immunomodulatory molecules; and outline biomaterial-based strategies to prime anti-cancer immune responses. Specifically, we focus on two widely used forms of biomaterials, multifunctional nanoparticles and biocompatible scaffolds.N

Advances in Nanoparticles for Effective Delivery of RNA Therapeutics

© 2022, The Korean BioChip Society.RNA therapeutics, including messenger RNA (mRNA) and small interfering RNA (siRNA), are genetic materials that mediate the translation of genetic direction from genes to induce or inhibit specific protein production. Although the interest in RNA therapeutics is rising globally, the absence of an effective delivery system is an obstacle to the clinical application of RNA therapeutics. Additionally, immunogenicity, short duration of protein expression, unwanted enzymatic degradation, and insufficient cellular uptake could limit the therapeutic efficacy of RNA therapeutics. In this regard, novel platforms based on nanoparticles are crucial for delivering RNAs to the targeted site to increase efficiency without toxicity. In this review, the most recent status of nanoparticles as RNA delivery vectors, with a focus on polymeric nanoparticles, peptide-derived nanoparticles, inorganic nanoparticles, and hybrid nanoparticles, is discussed. These nanoparticular platforms can be utilized for safe and effective RNA delivery to augment therapeutic effects. Ultimately, RNA therapeutics encapsulated in nanoparticle-based carriers will be used to treat many diseases and save lives.11Nsciescopuskc

The Upregulation of Regenerative Activity for Extracellular Vesicles with Melatonin Modulation in Chemically Defined Media

Extracellular vesicles (EVs) derived from human mesenchymal stem cells (hMSCs) have been widely known to have therapeutic effects by representing characteristics of the origin cells as an alternative for cell-based therapeutics. Major limitations of EVs for clinical applications include low production yields, unknown effects from serum impurities, and relatively low bioactivities against dose. In this study, we proposed a cell modulation method with melatonin for human umbilical cord MSCs (hUCMSCs) cultured in serum-free chemically defined media (CDM) to eliminate the effects of serum-derived impurities and promote regeneration-related activities. miRNAs highly associated with regeneration were selected and the expression levels of them were comparatively analyzed among various types of EVs depending on culture conditions. The EVs derived from melatonin-stimulated hUCMSCs in CDM (CDM mEVs) showed the highest expression levels of regeneration-related miRNAs, and 7 times more hsa-let-7b-5p, 5.6 times more hsa-miR-23a-3p, and 5.7 times more hsa-miR-100-5p than others, respectively. In addition, the upregulation of various functionalities, such as wound healing, angiogenesis, anti-inflammation, ROS scavenging, and anti-apoptosis, were proven using in vitro assays by simulating the characteristics of EVs with bioinformatics analysis. The present results suggest that the highly regenerative properties of hUCMSC-derived EVs were accomplished with melatonin stimulation in CDM and provided the potential for clinical uses of EVs