The recent emergence of nanomedicine has revolutionized the therapeutic landscape and necessitated the creation of more sophisticated drug delivery systems. Polymeric nanoparticles sit at the forefront of numerous promising drug delivery designs, due to their unmatched control over physiochemical properties such as size, shape, architecture, charge, and surface functionality. Furthermore, polymeric nanoparticles have the ability to navigate various biological barriers to precisely target specific sites within the body, encapsulate a diverse range of therapeutic cargo and efficiently release this cargo in response to internal and external stimuli. However, despite these remarkable advantages, the presence of polymeric nanoparticles in wider clinical application is minimal. This review will provide a comprehensive understanding of polymeric nanoparticles as drug delivery vehicles. The biological barriers affecting drug delivery will be outlined first, followed by a comprehensive description of the various nanoparticle designs and preparation methods, beginning with the polymers on which they are based. The review will meticulously explore the current performance of polymeric nanoparticles against a myriad of diseases including cancer, viral and bacterial infections, before finally evaluating the advantages and crucial challenges that will determine their wider clinical potential in the decades to come.

Polymeric Nanoparticles for Drug Delivery.

Extracellular vesicles (EVs) such as ectosomes and exosomes have gained attention as promising natural carriers for drug delivery. Exosomes, which range from 30 to 100 nm in diameter, possess a lipid bilayer and are secreted by various cells. Due to their high biocompatibility, stability, and low immunogenicity, exosomes are favored as cargo carriers. The lipid bilayer membrane of exosomes also offers protection against cargo degradation, making them a desirable candidate for drug delivery. However, loading cargo into exosomes remains to be a challenge. Despite various strategies such as incubation, electroporation, sonication, extrusion, freeze–thaw cycling, and transfection that have been developed to facilitate cargo loading, inadequate efficiency still persists. This review offers an overview of current cargo delivery strategies using exosomes and summarizes recent approaches for loading small-molecule, nucleic acid, and protein drugs into exosomes. With insights from these studies, we provide ideas for more efficient and effective delivery of drug molecules by using exosomes.

/pdf/current-strategies-for-exosome-cargo-loading-and-targeting-11ciqmtj.pdf

Current Strategies for Exosome Cargo Loading and Targeting Delivery

https://doi.org/10.1016/j.bioactmat.2023.05.018

M2 macrophage-derived exosomes promote diabetic fracture healing by acting as an immunomodulator

As the global population ages, bone‐related diseases have increasingly become a major social problem threatening human health. Exosomes, as natural cell products, have been used to treat bone‐related diseases due to their superior biocompatibility, biological barrier penetration, and therapeutic effects. Moreover, the modified exosomes exhibit strong bone‐targeting capabilities that may improve efficacy and avoid systemic side effects, demonstrating promising translational potential. However, a review of bone‐targeted exosomes is still lacking. Thus, the recently developed exosomes for bone‐targeting applications in this review are focused. The biogenesis and bone‐targeting regulatory functions of exosomes, the constructive strategies of modified exosomes to improve bone‐targeting, and their therapeutic effects for bone‐related diseases are introduced. By summarizing developments and challenges in bone‐targeted exosomes, It is striven to shed light on the selection of exosome constructive strategies for different bone diseases and highlight their translational potential for future clinical orthopedics.

Bone‐Targeted Exosomes: Strategies and Applications

The progress in human disease treatment can be greatly advanced through the implementation of nanomedicine. This approach involves targeted and cell-specific therapy, controlled drug release, personalized dosage forms, wearable drug delivery, and companion diagnostics. By integrating cutting-edge technologies with drug delivery systems, greater precision can be achieved at the tissue and cellular levels through the use of stimuli-responsive nanoparticles, and the development of electrochemical sensor systems. This precision targeting – by virtue of nanotechnology – allows for therapy to be directed specifically to affected tissues while greatly reducing side effects on healthy tissues. As such, nanomedicine has the potential to transform the treatment of conditions such as cancer, genetic diseases, and chronic illnesses by facilitating precise and cell-specific drug delivery. Additionally, personalized dosage forms and wearable devices offer the ability to tailor treatment to the unique needs of each patient, thereby increasing therapeutic effectiveness and compliance. Companion diagnostics further enable efficient monitoring of treatment response, enabling customized adjustments to the treatment plan. The question of whether all the potential therapeutic approaches outlined here are viable alternatives to current treatments is also discussed. In general, the application of nanotechnology in the field of biomedicine may provide a strong alternative to existing treatments for several reasons. In this review, we aim to present evidence that, although in early stages, fully merging advanced technology with innovative drug delivery shows promise for successful implementation across various disease areas, including cancer and genetic or chronic diseases. 

Biologics, theranostics, and personalized medicine in drug delivery systems.

http://www.cell.com/article/S2666379122004451/pdf

Exosome-based bone-targeting drug delivery alleviates impaired osteoblastic bone formation and bone loss in inflammatory bowel diseases

Currently, biological membrane-derived nanoparticles (NPs) have shown enormous potential as drug delivery vehicles due to their outstanding biomimetic properties. To make these NPs more adaptive to complex biological systems, some methods have been developed to modify biomembranes and endow them with more functions while preserving their inherent natures. In this review, we introduce five common approaches used for biomembrane decoration: membrane hybridization, the postinsertion method, chemical methods, metabolism engineering and gene engineering. These methods can functionalize a series of biomembranes derived from red blood cells, white blood cells, tumor cells, platelets, exosomes and so on. Biomembrane engineering could markedly facilitate the targeted drug delivery, treatment and diagnosis of cancer, inflammation, immunological diseases, bone diseases and Alzheimer's disease. It is anticipated that these membrane modification techniques will advance biomembrane-derived NPs into broader applications in the future.

/pdf/engineered-biomembrane-derived-nanoparticles-for-nanoscale-lodqqior.pdf

Engineered biomembrane-derived nanoparticles for nanoscale theranostics

Intra-articular nanodrug delivery strategies for treating osteoarthritis.

Cancer remains a severe public health burden worldwide. One of the challenges hampering effective cancer therapy is that the existing cancer models hardly recapitulate the tumor microenvironment of human patients. Over the past decade, tumor organoids have emerged as an in vitro 3D tumor model to mimic the pathophysiological characteristics of parental tumors. Various techniques have been developed to construct tumor organoids, such as matrix-based methods, hanging drop, spinner or rotating flask, nonadhesive surface, organ-on-a-chip, 3D bioprinting, and genetic engineering. This review elaborated on cell components and fabrication methods for establishing tumor organoid models. Furthermore, we discussed the application of tumor organoids to cancer modeling, basic cancer research, and anticancer therapy. Finally, we discussed current limitations and future directions in employing tumor organoids for more extensive applications.

Construction of tumor organoids and their application to cancer research and therapy

Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery, as demonstrated by the approval of patisiran for amyloidosis therapy in 2018. To illuminate the unique superiority of lipid nanovehicles in RNA delivery, in this review, we first introduce various RNA therapeutics, describe systemic delivery barriers, and explain the lipid components and methods used for lipid nanovehicle preparation. Then, we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery. Finally, the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed. Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery, inspiring the development of more high-performance RNA lipid nanovesicles in the future. 

Lipid nanovehicles overcome barriers to systemic RNA delivery: Lipid components, fabrication methods, and rational design

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