Poly(ethylene glycol) (PEG) is widely used as a gold standard in bioconjugation and nanomedicine to prolong blood circulation time and improve drug efficacy. The conjugation of PEG to proteins, peptides, oligonucleotides (DNA, small interfering RNA (siRNA), microRNA (miRNA)) and nanoparticles is a well-established technique known as PEGylation, with PEGylated products have been using in clinics for the last few decades. However, it is increasingly recognized that treating patients with PEGylated drugs can lead to the formation of antibodies that specifically recognize and bind to PEG (i.e., anti-PEG antibodies). Anti-PEG antibodies are also found in patients who have never been treated with PEGylated drugs but have consumed products containing PEG. Consequently, treating patients who have acquired anti-PEG antibodies with PEGylated drugs results in accelerated blood clearance, low drug efficacy, hypersensitivity, and, in some cases, life-threatening side effects. In this succinct review, we collate recent literature to draw the attention of polymer chemists to the issue of PEG immunogenicity in drug delivery and bioconjugation, thereby highlighting the importance of developing alternative polymers to replace PEG. Several promising yet imperfect alternatives to PEG are also discussed. To achieve asatisfactory alternative, further joint efforts of polymer chemists and scientists in related fields are urgently needed to design, synthesize and evaluate new alternatives to PEG.

https://www.mdpi.com/2073-4360/12/2/298/pdf

The Importance of Poly(ethylene glycol) Alternatives for Overcoming PEG Immunogenicity in Drug Delivery and Bioconjugation.

Studies of nanosized forms of bismuth (Bi)-containing materials have recently expanded from optical, chemical, electronic, and engineering fields towards biomedicine, as a result of their safety, cost-effective fabrication processes, large surface area, high stability, and high versatility in terms of shape, size, and porosity. Bi, as a nontoxic and inexpensive diamagnetic heavy metal, has been used for the fabrication of various nanoparticles (NPs) with unique structural, physicochemical, and compositional features to combine various properties, such as a favourably high X-ray attenuation coefficient and near-infrared (NIR) absorbance, excellent light-to-heat conversion efficiency, and a long circulation half-life. These features have rendered bismuth-containing nanoparticles (BiNPs) with desirable performance for combined cancer therapy, photothermal and radiation therapy (RT), multimodal imaging, theranostics, drug delivery, biosensing, and tissue engineering. Bismuth oxyhalides (BiOx, where X is Cl, Br or I) and bismuth chalcogenides, including bismuth oxide, bismuth sulfide, bismuth selenide, and bismuth telluride, have been heavily investigated for therapeutic purposes. The pharmacokinetics of these BiNPs can be easily improved via the facile modification of their surfaces with biocompatible polymers and proteins, resulting in enhanced colloidal stability, extended blood circulation, and reduced toxicity. Desirable antibacterial effects, bone regeneration potential, and tumor growth suppression under NIR laser radiation are the main biomedical research areas involving BiNPs that have opened up a new paradigm for their future clinical translation. This review emphasizes the synthesis and state-of-the-art progress related to the biomedical applications of BiNPs with different structures, sizes, and compositions. Furthermore, a comprehensive discussion focusing on challenges and future opportunities is presented.

/pdf/the-versatile-biomedical-applications-of-bismuth-based-4weqqirlrh.pdf

The versatile biomedical applications of bismuth-based nanoparticles and composites: therapeutic, diagnostic, biosensing, and regenerative properties

In the last decades, the staggering progress in nanotechnology brought around a wide and heterogeneous range of nanoparticle-based platforms for the diagnosis and treatment of many diseases. Most of these systems are designed to be administered intravenously. This administration route allows the nanoparticles (NPs) to widely distribute in the body and reach deep organs without invasive techniques. When these nanovectors encounter the biological environment of systemic circulation, a dynamic interplay occurs between the circulating proteins and the NPs, themselves. The set of proteins that bind to the NP surface is referred to as the protein corona (PC). PC has a critical role in making the particles easily recognized by the innate immune system, causing their quick clearance by phagocytic cells located in organs such as the lungs, liver, and spleen. For the same reason, PC defines the immunogenicity of NPs by priming the immune response to them and, ultimately, their immunological toxicity. Furthermore, the protein corona can cause the physical destabilization and agglomeration of particles. These problems induced to consider the PC only as a biological barrier to overcome in order to achieve efficient NP-based targeting. This review will discuss the latest advances in the characterization of PC, development of stealthy NP formulations, as well as the manipulation and employment of PC as an alternative resource for prolonging NP half-life, as well as its use in diagnostic applications.

Recent Advances in Understanding the Protein Corona of Nanoparticles and in the Formulation of "Stealthy" Nanomaterials.

Cell membrane coating technology is an approach to the biomimetic replication of cell membrane properties, and is an active area of ongoing research readily applicable to nanoscale biomedicine. Nanoparticles (NPs) coated with cell membranes offer an opportunity to unite natural cell membrane properties with those of the artificial inner core material. The coated NPs not only increase their biocompatibility but also achieve effective and extended circulation in vivo, allowing for the execution of targeted functions. Although cell membrane-coated NPs offer clear advantages, much work remains before they can be applied in clinical practice. In this review, we first provide a comprehensive overview of the theory of cell membrane coating technology, followed by a summary of the existing preparation and characterization techniques. Next, we focus on the functions and applications of various cell membrane types. In addition, we collate model drugs used in cell membrane coating technology, and review the patent applications related to this technology from the past 10 years. Finally, we survey future challenges and trends pertaining to this technology in an effort to provide a comprehensive overview of the future development of cell membrane coating technology.

/pdf/cell-membrane-coating-technology-a-promising-strategy-for-1zwtwubxb7.pdf

Cell Membrane Coating Technology: A Promising Strategy for Biomedical Applications

Hybrid cell membrane-coated nanoparticles: A multifunctional biomimetic platform for cancer diagnosis and therapy.

Red blood cell membrane-camouflaged nanoparticles: a novel drug delivery system for antitumor application.

Background: Psoriasis is a common chronic inflammatory skin disease. Its treatment is challenged by the limited amount of drug reaching the inflamed skin. The overexpressed CD44 protein in inflamed psoriatic skin can serve as a potential target of novel active-targeting nanocarriers to increase drug accumulation in the skin. Methods: Hyaluronic acid (HA) was linked to propylene glycol-based ethosomes by covalent binding to develop a novel topical drug delivery carrier (HA-ES) for curcumin. An imiquimod-induced psoriasis mouse model was established, and curcumin delivery and anti-psoriatic efficacy using HA-ES were compared with those using plain ethosomes (ES). Results: The HA gel network formed on the surface of HA-ES reduced the leakage and release of poorly water-soluble curcumin. Compared with ES, transdermal curcumin delivery was significantly enhanced by using HA-ES as vehicles; the cumulative transdermal amount and the amount retained in the skin in vitro after 8 h were, respectively, 1.6 and 1.4 times those observed with ES, as well as 3.1 and 3.3 times those observed with a curcumin propylene glycol solution (PGS), respectively. The in vivo psoriatic skin retention of curcumin with HA-ES was 2.3 and 4.0 times that of ES and PGS, respectively. CD44 expression in imiquimod-induced psoriasis-like inflamed skin was 2.7 times that in normal skin. Immunostaining revealed similar results, suggesting that the specific adhesion of HA-ES to CD44 increased drug accumulation in the skin. After topical administration to mice, the HA-ES group showed an alleviation of inflammation symptoms; lower TNF-α, IL-17A, IL-17F, IL-22, and IL-1β mRNA levels; and lower CCR6 protein expression compared to the ES and PGS groups. Conclusion: We demonstrated increased topical drug delivery of curcumin to inflamed tissues using HA-ES targeting the highly expressed CD44 protein. This innovative strategy could be applied for the development of topical drug delivery systems targeting inflamed skin.

CD44 Assists the Topical Anti-Psoriatic Efficacy of Curcumin-Loaded Hyaluronan-Modified Ethosomes: A New Strategy for Clustering Drug in Inflammatory Skin.

Co-delivery of evodiamine and rutaecarpine in a microemulsion-based hyaluronic acid hydrogel for enhanced analgesic effects on mouse pain models.

Folic acid modified lipid-bilayer coated mesoporous silica nanoparticles co-loading paclitaxel and tanshinone IIA for the treatment of acute promyelocytic leukemia.

Qing Xia

Papers

Red blood cell membrane-camouflaged nanoparticles: a novel drug delivery system for antitumor application.

CD44 Assists the Topical Anti-Psoriatic Efficacy of Curcumin-Loaded Hyaluronan-Modified Ethosomes: A New Strategy for Clustering Drug in Inflammatory Skin.

Co-delivery of evodiamine and rutaecarpine in a microemulsion-based hyaluronic acid hydrogel for enhanced analgesic effects on mouse pain models.

Folic acid modified lipid-bilayer coated mesoporous silica nanoparticles co-loading paclitaxel and tanshinone IIA for the treatment of acute promyelocytic leukemia.

Tumor cell membrane-derived nano-Trojan horses encapsulating phototherapy and chemotherapy are accepted by homologous tumor cells.