Review Nanomedicine (Lond). 2016 Apr;11(7):851-65. doi: 10.2217/nnm.16.28. Gold nanoparticle surface functionalization: mixed monolayer versus hetero bifunctional peg linker Abstract To create a clinically relevant gold nanoparticle (AuNP) treatment, the surface must be functionalized with multiple ligands such as drugs, antifouling agents and targeting moieties. However, attaching several ligands of differing chemistries and lengths, while ensuring they all retain their biological functionality remains a challenge. This review compares the two most widely employed methods of surface cofunctionalization, namely mixed monolayers and hetero-bifunctional linkers. While there are numerous in vitro studies successfully utilizing both surface arrangements, there is little consensus regarding their relative merits. Animal and preclinical studies have demonstrated the effectiveness of mixed monolayer functionalization and while some promising in vitro results have been reported for PEG linker capped AuNPs, any potential benefits of the approach are not yet fully understood.

Int J Nanomedicine. 2023 Mar 30:18:1615-1630. doi: 10.2147/IJN.S402418. eCollection 2023. Effects of PEG-Linker Chain Length of Folate-Linked Liposomal Formulations on Targeting Ability and Antitumor Activity of Encapsulated Drug Abstract Introduction: Ligand-conjugated liposomes are promising for the treatment of specific receptor-overexpressing cancers. However, previous studies have shown inconsistent results because of the varying properties of the ligand, presence of a polyethylene glycol (PEG) coating on the liposome, length of the linker, and density of the ligand. Methods: Here, we prepared PEGylated liposomes using PEG-linkers of various lengths conjugated with folate and evaluated the effect of the PEG-linker length on the nanoparticle distribution and pharmacological efficacy of the encapsulated drug both in vitro and in vivo. Results: When folate was conjugated to the liposome surface, the cellular uptake efficiency in folate receptor overexpressed KB cells dramatically increased compared to that of the normal liposome. However, when comparing the effect of the PEG-linker length in vitro, no significant difference between the formulations was observed. In contrast, the level of tumor accumulation of particles in vivo significantly increased when the length of the PEG-linker was increased. The tumor size was reduced by >40% in the Dox/FL-10K-treated group compared to that in the Dox/FL-2K- or 5K-treated groups. Discussion: Our study suggests that as the length of PEG-linker increases, the tumor-targeting ability can be enhanced under in vivo conditions, which can lead to an increase in the antitumor activity of the encapsulated drug. Keywords: PEG-linker length; PEGylated liposome; folate receptor; ligand-conjugated liposome.

At the forefront of modern drug development, polyethylene glycol (PEG) derivatives play a crucial role. They act like an "invisibility cloak" for drug molecules, significantly enhancing therapeutic efficacy and safety, representing a revolutionary technology in the field of pharmaceutical chemistry.     1. What are Polyethylene Glycol (PEG) Derivatives?   Polyethylene Glycol (PEG) is a linear, water-soluble, highly biocompatible polymer synthesized from the polymerization of ethylene oxide. It is non-toxic, non-immunogenic, and has been approved by the U.S. FDA as a safe chemical substance for oral, injectable, and topical use.   PEG derivatives specifically refer to those PEG molecules that have been chemically modified to carry specific reactive functional groups (e.g., amino, carboxyl, maleimide, N-hydroxysuccinimide ester) at one or both ends of their molecular chains. These functional groups act like "grappling hands," enabling covalent binding to specific groups (e.g., amino, thiol groups) on proteins, peptides, antibodies, small molecule drugs, and even nanoparticles (like liposomes).   This process is known as "PEGylation". Through PEGylation, one or more PEG chains are attached to the drug molecule, fundamentally altering its physicochemical properties and in vivo behavior.     2. Applications in Modern Medicine   As a mature drug delivery and improvement strategy, PEGylation technology is extremely widespread in modern medicine, primarily serving the following purposes:   Increase Drug Solubility: Many hydrophobic drugs have poor solubility in water, making them difficult to formulate into injectable solutions. Attaching hydrophilic PEG chains can significantly enhance a drug's aqueous solubility.   Prolong Half-life, Reduce Dosing Frequency: ①Increase Molecular Size: The addition of PEG chains significantly increases the drug's molecular weight, making it less likely to be filtered through the glomeruli, thereby slowing renal clearance. ②Reduce Immune Recognition: The PEG chain acts like a protective shield, enveloping the drug surface, masking its antigenic epitopes, and reducing the chance of recognition and clearance by the immune system. ③Hinder Enzymatic Degradation: This same shielding effect also reduces the rate at which the drug is degraded by hydrolytic enzymes like proteases.   Reduce Immunogenicity and Toxicity:For protein-based drugs (e.g., enzymes, cytokines), PEGylation can mask their heterologous nature, reducing the likelihood of the body producing antibodies, thus minimizing allergic reactions. It can also modify toxic functional groups of certain drugs, improving their safety profile (therapeutic window).   Enhance Targeting (Passive Targeting): By prolonging the drug's circulation time in the bloodstream via PEGylation, the drug is more likely to accumulate in tissues with leaky vasculature, such as tumors or inflamed sites, through the Enhanced P...

Review Zhejiang Da Xue Xue Bao Yi Xue Ban. 2022 Apr 25;51(2):185-191. doi: 10.3724/zdxbyxb-2022-0047. Research advance in lipid nanoparticle-mRNA delivery system and its application in CAR-T cell therapy Abstract Chimeric antigen receptor (CAR) T cell therapy has shown significant efficacy for hematological malignancies, however, it needs to be further optimized. Recently, the lipid nanoparticle (LNP)-mRNA delivery system as a nonviral gene transfer vector has gained rapid progress in CAR-T cell therapy. The claudin-6 (CLDN6) mRNA is delivered to antigen presenting cells (APCs) through LNP system, thereby enhancing the function of CLDN6 CAR-T cells for the clearance of solid tumor cells. For treatment of acute cardiac injury, the fibroblast activation protein (FAP) CAR mRNA can be delivered to T cells through LNP system for the in vivo production of FAP CAR-T cells, thereby blocking the process of myocardial fibrosis. The LNP-mRNA delivery system has advantages including having no integration in host genome, inexpensiveness, low toxicity and modifiability; on the other hand, it has certain disadvantages such as limited cell persistence caused by transient protein expression and limitations in preparation techniques. This article reviews the research advance in LNP-mRNA in vivo delivery system and its application in CAR-T cell therapy. Keywords: Chimeric antigen receptor T cell; Gene transfer vector; Lipid nanoparticle; Messenger RNA; Review; delivery system. For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

J Control Release. 2024 Sep:373:952-961. doi: 10.1016/j.jconrel.2024.07.046. Epub 2024 Aug 8. A perspective on bleb and empty LNP structures Abstract Although lipid nanoparticles (LNPs) have been FDA-approved for mRNA delivery, there is still much to learn about these fascinating multi-component delivery systems. Here, I discuss the presence of "bleb" structures on LNPs and the co-existence of mRNA-empty LNPs in LNP-mRNA-based formulations. Specifically, I discuss key articles on these structural and compositional heterogeneities, whether these features present negative or positive LNP attributes, and how to deal with them in research and quality control settings. Additionally, I present current approaches and propose novel strategies on how to study and quantify bleb and empty LNP structures. With the conflicting views on these features in the literature and limited systematic studies on their impact on safety and efficacy, I hope this Perspective will support current and bring forward new thinking about these matters. I anticipate that novel studies and insights could emerge from these lines of thinking, which could potentially enhance the development of safe and efficient LNP-based drug products that will either embrace, leverage, or mitigate the presence of blebs and empty LNPs. Keywords: Bleb; Empty; LNP; Lipid nanoparticles; Quantifcation; Structures. For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

J Control Release. 2021 Jul 10:335:237-246. doi: 10.1016/j.jconrel.2021.05.021. Epub 2021 May 18. Impact of lipid nanoparticle size on mRNA vaccine immunogenicity Abstract Lipid nanoparticles (LNP) are effective delivery vehicles for messenger RNA (mRNA) and have shown promise for vaccine applications. Yet there are no published reports detailing how LNP biophysical properties can impact vaccine performance. In our hands, a retrospective analysis of mRNA LNP vaccine in vivo studies revealed a relationship between LNP particle size and immunogenicity in mice using LNPs of various compositions. To further investigate this, we designed a series of studies to systematically change LNP particle size without altering lipid composition and evaluated biophysical properties and immunogenicity of the resulting LNPs. While small diameter LNPs were substantially less immunogenic in mice, all particle sizes tested yielded a robust immune response in non-human primates (NHP). Keywords: Lipid; Nanoparticle; Size; Vaccine; mRNA. For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

Review Mol Ther. 2017 Jul 5;25(7):1467-1475.   doi: 10.1016/j.ymthe.2017.03.013.   Epub 2017 Apr 13. Lipid Nanoparticle Systems for Enabling Gene Therapies Abstract Genetic drugs such as small interfering RNA (siRNA), mRNA, or plasmid DNA provide potential gene therapies to treat most diseases by silencing pathological genes, expressing therapeutic proteins, or through gene-editing applications.   In order for genetic drugs to be used clinically, however, sophisticated delivery systems are required.   Lipid nanoparticle (LNP) systems are currently the lead non-viral delivery systems for enabling the clinical potential of genetic drugs.   Application will be made to the Food and Drug Administration (FDA) in 2017 for approval of an LNP siRNA drug to treat transthyretin-induced amyloidosis, presently an untreatable disease.   Here, we first review research leading to the development of LNP siRNA systems capable of silencing target genes in hepatocytes following systemic administration.   Subsequently, progress made to extend LNP technology to mRNA and plasmids for protein replacement, vaccine, and gene-editing applications is summarized.   Finally, we address current limitations of LNP technology as applied to genetic drugs and ways in which such limitations may be overcome.   It is concluded that LNP technology, by virtue of robust and efficient formulation processes, as well as advantages in potency, payload, and design flexibility, will be a dominant non-viral technology to enable the enormous potential of gene therapy. Keywords: gene editing;   gene therapy;   genetic drugs;   lipid nanoparticles;   mRNA;   siRNA. For more product information, please contact us at: US Tel: 1-844-782-5734 US Tel: 1-844-QUAL-PEG CHN Tel: 400-918-9898 Email: sales@sinopeg.com

Imagine tiny piezoelectric force sensors that can be placed inside the body: they monitor physiological pressure changes in damaged organs, aid precise drug delivery, or promote tissue repair and regeneration. The best part? They require no battery power, and after use, the body absorbs and degrades them, eliminating the need for invasive removal surgery! However, traditional piezoelectric materials like inorganic ceramics and organic polymers suffer from inadequate degradability and cytotoxicity. Scientists identified amino acid crystals as a promising candidate – they are biocompatible and exhibit excellent piezoelectric properties. The challenge? These crystals are too small, like scattered sand, making it extremely difficult to align them into functional devices. Researchers Yi Cao and Bin Xue from Nanjing University found a solution: a special technique called "Mechanical Annealing". Using natural amino acid crystals as the piezoelectric material, they engineered fully organic, biodegradable piezoelectric force sensors. When treated with mechanical annealing, the crystals' power generation capability skyrocketed – achieving a piezoelectric coefficient 12 times higher than that of single-crystal powders! Furthermore, the treated crystal films became smooth and flat, like a phone screen protector, significantly improving contact with the electrodes and enabling stronger, more stable electrical signals. The resulting "absorbable piezoelectric force sensors", once packaged, were implanted in vivo and successfully monitored dynamic movements like muscle contractions and lung respiration continuously for 4 weeks. Afterwards, they gradually degraded without causing inflammation or systemic toxicity. This breakthrough offers new hope for future medicine, providing a pathway to design and manufacture fully organic, biodegradable force sensors for potential clinical applications! Fabrication of the Packaged Force Sensor: Preparation of Mechanically Annealed Crystal Films: Isoleucine was dissolved in deionized water to form a solution, heated, then transferred to an ice-water bath to stand, allowing crystal nuclei to form. The crystals were then collected and dried in an oven. The prepared isoleucine crystals were filled into a tablet mold and subjected to the mechanical annealing process, resulting in round, film-like crystals. Other amino acid crystals and their mechanically annealed counterparts were prepared using the same method. PLA-PAN Electrode Preparation: Polylactic acid (PLA) was dissolved in dichloromethane (DCM) to form PLA films, serving as the sensor's outer "protective membrane". But a membrane alone isn't enough; sensors need electrodes to collect weak electrical signals. The researchers had a clever trick: they immersed one side of the PLA film in a "reactive solution" (containing sulfuric acid and aniline). After processing, the originally insulating PLA film surface became coated with a conductive layer of polyaniline (PAN...