Journal of Controlled Release

RNA therapies have recently taken a giant leap forward with the approval of Onpattro™, a siRNA therapy delivered using a lipid nanoparticle (LNP), and the LNP-enabled mRNA vaccines against COVID19, which are the first mRNA drugs to reach the marketplace. The latter medicines have illustrated that stability is a significant challenge in the distribution of RNA drugs using non-viral delivery systems, particularly in areas without cold chain storage. Here, we describe a proof-of-concept study on the engineering of an LNP mRNA formulation suitable for spray drying...

The spine is the most common site of bone metastases, as 20%-40% of cancer patients suffer from spinal metastases. Treatments for spinal metastases are scarce and palliative, primarily aiming at relieving bone pain and preserving neurological function. The bioactive agents-mediated therapies are the most effective modalities for treating spinal metastases because they achieve systematic and specific tumor regression. However, the clinical applications of some bioactive agents are limited due to the lack of targeting capabilities, severe side effects, and vulnerability of drug resistance...

Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disorder that affects the entire gastrointestinal tract and is associated with an increased risk of colorectal cancer. Mainstream clinical testing methods are time-consuming, painful for patients, and insufficiently sensitive to detect early symptoms. Currently, there is no definitive cure for IBD, and frequent doses of medications with potentially severe side effects may affect patient response. In recent years, nanomaterials have demonstrated considerable potential for IBD management due to their diverse structures, composition, and physical and chemical properties...

RNA-based therapeutics have emerged as promising approaches to modulate gene expression and generate therapeutic proteins or antigens capable of inducing immune responses to treat a variety of diseases, such as infectious diseases, cancers, immunologic disorders, and genetic disorders. However, the efficient delivery of RNA molecules into cells poses significant challenges due to their large molecular weight, negative charge, and susceptibility to degradation by RNase enzymes. To overcome these obstacles, viral and non-viral vectors have been developed, including lipid nanoparticles, viral vectors, proteins, dendritic macromolecules, among others...

There is increasing evidence that malignant tumors are initiated and maintained by a sub-population of tumor cells that have similar biological properties to normal adult stem cells. This very small population of Cancer Stem Cells (CSC) comprises tumor initiating cells responsible for cancer recurrence, drug resistance and metastasis. Conventional treatments such as chemotherapy, radiotherapy and surgery, in addition to being potentially toxic and non-specific, may paradoxically increase the population, spread and survival of CSCs...

Extracellular vesicles (EVs) are promising therapeutic carriers owing to their ideal size range and intrinsic biocompatibility. However, limited targeting ability has caused major setbacks in the clinical application of EV therapeutics. To overcome this, we genetically engineered natural free streptavidin (SA) on the cellular surface of bone marrow mesenchymal stem cells (BMSCs) and obtained typical EVs from these cells (BMSC-EVs). Biotin-coated gold nanoparticles confirmed the expression of SA on the membrane of EVs, which has a high affinity for biotinylated molecules...

Extracellular vesicles (EVs) play a pivotal role in intercellular communication and have been implicated in cancer progression. Hypoxia, a pervasive hallmark of cancer, is known to regulate EV biogenesis and function. Hypoxic EVs contain a specific set of proteins, nucleic acids, lipids, and metabolites, capable of reprogramming the biology and fate of recipient cells. Enhancing the intrinsic therapeutic efficacy of EVs can be achieved by strategically modifying their structure and contents. Moreover, the use of EVs as drug delivery vehicles holds great promise for cancer treatment...

Wound healing is a crucial process that restores the integrity and function of the skin and other tissues after injury. However, external factors, such as infection and inflammation, can impair wound healing and cause severe tissue damage. Therefore, developing new drugs or methods to promote wound healing is of great significance. Photothermal therapy (PTT) is a promising technique that uses photothermal agents (PTAs) to convert near-infrared radiation into heat, which can eliminate bacteria and stimulate tissue regeneration...

Unmet medical needs in the treatment of critical-size bone defects have led to the development of numerous innovative bone tissue engineering implants over the years. Although additive manufacturing allows flexible patient-specific treatments by modifying topological properties with various materials, the development of ideal bone implants that aid new tissue regeneration and reduce post-implantation bone disorders has been limited. Exhibiting good safety profiles, natural biomolecules are gaining the attention of the health industry, providing equivalent or superior performances when compared to more expensive growth factors and synthetic drugs...

The gut microbiota is closely associated with the progression of colorectal cancer (CRC) in which Fusobacterium nucleatum (F. nucleatum) was found to induce cancer resistance to chemotherapeutics. To relieve F. nucleatum-induced drug resistance, herein, we found that short-chain fatty acid butyrate can inhibit the growth, enrichment and adhesion of F. nucleatum in colorectal cancer tissues by downregulating the expression of adhesion-associated outer membrane proteins, including RadD, FomA, and FadA, to reduce the colonization and invasion of F...

Polyurethanes are a versatile and highly tunable class of materials that possess unique properties including high tensile strength, abrasion and fatigue resistance, and flexibility at low temperatures. The tunability of polyurethane properties has allowed this class of polymers to become ubiquitous in our daily lives in fields as diverse as apparel, appliances, construction, and the automotive industry. Additionally, polyurethanes with excellent biocompatibility and hemocompatibility can be synthesized, enabling their use as biomaterials in the medical field...

The effectiveness of thermal ablation for the treatment of liver tumours is limited by the risk of incomplete ablation, which can result in residual tumours. Herein, an enhancement strategy is proposed based on the controlled release of Ganoderma applanatum polysaccharide (GAP) liposome-microbubble complexes (GLMCs) via ultrasound (US)-targeted microbubble destruction (UTMD) and sublethal hyperthermic (SH) field. GLMCs were prepared by conjugating GAP liposomes onto the surface of microbubbles via biotin-avidin linkage...

Exosomes are endosome-derived extracellular vesicles about 100 nm in diameter. They are emerging as promising delivery platforms due to their advantages in biocompatibility and engineerability. However, research into and applications for engineered exosomes are still limited to a few areas of medicine in mammals. Here, we expanded the scope of their applications to sex-determining gene studies in early vertebrates. An integrated strategy for constructing the exosome-based delivery system was developed for efficient regulation of dmrt1, which is one of the most widely used sex-determining genes in metazoans...

Although cationic liposomes are efficient carriers for nucleic acid delivery, their toxicity often hampers the clinical translation. Polyethylene glycol (PEG) coating has been largely used to improve their stability and reduce toxicity. Nevertheless, it has been found to decrease the transfection process. In order to exploit the advantages of cationic liposomes and PEG decoration for nucleic acid delivery, liposomes decorated with tetraArg-[G-1]-distearoyl glycerol (Arg4 -DAG) dendronic oligo-cationic lipid enhancer (OCE) and PEG-lipid have been investigated...

Pharmaceutical treatments are critical for the acute and subacute phases of spinal cord injury (SCI) and significantly impact patients' prognoses. However, there is a lack of a precise, multitemporal, integrated drug delivery system for medications administered in both phases. In this study, we prepare a hybrid polylysine-based hydrogel (PBHEVs @AGN) comprising short-term release of pH-responsive aminoguanidine nanoparticles (AGN) and sustained release of extracellular vesicles (EVs) for synergistic SCI treatment...

PEGylated nanomedicines have been extensively developed and applied to cancer therapy. However, the antitumor efficacy of these nanoparticles is hampered by the accelerated blood clearance (ABC) effect caused by anti-PEG antibodies in vivo. There is still limited understanding about the cause of pre-existing anti-PEG antibodies in the human body. Herein, we discovered that PEG-based pharmaceutical excipients, commonly used in clinical and daily settings, could induce anti-PEG antibodies in vivo and lead to considerable potential clinical impacts on pharmacokinetics and pharmacodynamics of PEGylated nanoparticles...

It is time for the story of mitochondria and intracellular communication in multidrug resistant cancer to be rewritten. Herein we characterize the extent and cellular advantages of mitochondrial network fusion in multidrug resistant (MDR) breast cancer and have designed a novel nanomedicine that disrupts mitochondrial network fusion and systematically manipulates organelle fusion and function. Combination Organelle Mitochondrial Endoplasmic reticulum Therapy (COMET) is an innovative translational nanomedicine for treating MDR triple negative breast cancer (TNBC) that has superior safety and equivalent efficacy to the current standard of care (paclitaxel)...

Checkpoint blockade immunotherapy (CBI) have exhibited remarkable benefits for cancer therapy. However, the low responsivity of CBI hinders its application in treatment of bladder cancer. Ferroptosis shows potential for increasing the responsivity of CBI by inducing immunogenic cell death (ICD) process. Herein, we developed a mitochondrial-targeted liposome loaded with brequinar (BQR) (BQR@MLipo) for enhancing the mitochondrial-related ferroptosis in bladder cancer in situ. It could be found that BQR@MLipo could selectively accumulate into mitochondria and inactivate dihydroorotate dehydrogenase (DHODH), which induced extensive mitochondrial lipid peroxidation and ROS, finally triggering ferroptosis of bladder cancer cells to boost the release of intracellular damage-associated molecular patterns (DAMPs) such as calreticulin (CRT), adenosine triphosphate (ATP), high mobility group box 1 (HMGB1)...

Different types of ibuprofen-loaded, poly (D,L lactic-co-glycolic acid) (PLGA)-based implants were prepared by 3D printing (Droplet Deposition Modeling). The theoretical filling density of the mesh-shaped implants was varied from 10 to 100%. Drug release was measured in agarose gels and in well agitated phosphate buffer pH 7.4. The key properties of the implants (and dynamic changes thereof upon exposure to the release media) were monitored using gravimetric measurements, optical microscopy, Differential Scanning Calorimetry, Gel Permeation Chromatography, and Scanning Electron Microscopy...

Nanovesicles and bio-vesicles (BVs) have emerged as promising tools to achieve targeted cancer therapy due to their ability to overcome many of the key challenges currently being faced with conventional chemotherapy. These challenges include the diverse and often complex pathophysiology involving the progression of cancer, as well as the various biological barriers that circumvent therapeutic molecules reaching their target site in optimum concentration. The scientific evidence suggests that surface-functionalized nanovesicles and BVs camouflaged nano-carriers (NCs) both can bypass the established biological barriers and facilitate fourth-generation targeting for the improved regimen of treatment...