Intracellular mechanistic insights into cRGD-modified BiSe nanofoams for enhanced photothermal therapy via exocytosis inhibition.

The cRGD peptide surface coating strategy for photothermal therapy nanoplatforms shows great promise in developing safe and effective cancer therapies. However, the precise intracellular mechanisms of these platforms remain unclear due to the complexity of intracellular trafficking and nano-bio interactions. This study investigates the nano-bio interactions of BiSe nanofoams, a representative photothermal therapy nanoplatform, coated with cRGD peptide in cancer cells, focusing on endocytosis, exocytosis, and cellular trafficking.

Microneedle technology for enhanced topical treatment of skin infections.

Skin infections caused by microbes such as bacteria, fungi, and viruses often lead to aberrant skin functions and appearance, eventually evolving into a significant risk to human health. Among different drug administration paradigms for skin infections, microneedles (MNs) have demonstrated superiority mainly because of their merits in enhancing drug delivery efficiency and reducing microbial resistance. Also, integrating biosensing functionality to MNs offers point-of-care wearable medical devices for analyzing specific pathogens, disease status, and drug pharmacokinetics, thus providing personalized therapy for skin infections.

"On-demand" nanosystem-integrated microneedles for amplified triple therapy against recalcitrant bacteria and biofilm growth.

Phototherapy has emerged to eradicate recalcitrant bacteria without causing drug resistance, but it is often accompanied by considerable limitations owing to a high tolerance of recalcitrant bacteria to heat and oxidative damage, leading to low efficiency of monotherapy and unwanted side effects. Assuming that employing antimicrobial peptides (AMPs) to disrupt bacterial membranes could reduce bacterial tolerance, a multifunctional "on-demand" nanosystem based on zeolitic imidazolate framework-8 (ZIF-8) with metal ions for intrinsic antibacterial activity was constructed to potently kill methicillin-resistant (MRSA). Then, microneedles (MNs) were used to transdermally deliver the ZIF-8-based nanosystem for localized skin infection.

Hydrogel local drug delivery systems for postsurgical management of tumors: and perspectives.

Surgery is one of the primary treatments for solid tumors. However, the incomplete resection of tumor cells and the immunosuppressive microenvironment make the issue of postsurgical tumor recurrence a great challenge. Furthermore, a wide range of requirements, including ensuring effective hemostasis, implementing prophylactic measures against infection, and promoting wound healing, were also raised in the postsurgical management of tumors.

Bimetallic peroxide-based nanotherapeutics for immunometabolic intervention and induction of immunogenic cell death to augment cancer immunotherapy.

Immunotherapy has transformed cancer treatment, but its efficacy is often limited by the immunosuppressive characteristics of the tumor microenvironment (TME), which are predominantly influenced by the metabolism of cancer cells. Among these metabolic pathways, the indoleamine 2,3-dioxygenase (IDO) pathway is particularly crucial, as it significantly contributes to TME suppression and influences immune cell activity. Additionally, inducing immunogenic cell death (ICD) in tumor cells can reverse the immunosuppressive TME, thereby enhancing the efficacy of immunotherapy.

Biomineralized catalytic nanoreactor integrated microneedle patch for on demand immunomodulator supply to combat psoriasis.

The endogenous immunomodulator adenosine (ADO) was expected to be potentialized as an efficacious mediator to combat psoriasis. However, its efficacy is severely hindered by its poor metabolic stability and insufficient accumulation at the dermatological lesions. In this study, a biomineralized catalytic nanoreactor was delicately customized by encapsulating ADO precursor (adenosine monophosphate, AMP) within the internal porous skeleton of zeolitic imidazolate framework-90, followed by the biomineralization of the AMP catabolic enzyme on the outer layer.

Development of Minodronic Acid-Loaded Dissolving Microneedles for Enhanced Osteoporosis Therapy: Influence of Drug Loading on the Bioavailability of Minodronic Acid.

Osteoporosis is a metabolic bone disorder with impaired bone microstructure and increased bone fractures, seriously affecting the quality of life of patients. Among various bisphosphonates prescribed for managing osteoporosis, minodronic acid (MA) is the most potent inhibitor of bone context resorption. However, oral MA tablet is the only commercialized dosage form that has extremely low bioavailability, severe adverse reactions, and poor patient compliance.

Nanocrystals: Versatile Platform for Traditional Chinese Medicine Delivery.

The medicinal value of Chinese medicines has been recognized since ancient times, and they have also been used to treat various diseases. However, in-depth studies on the active ingredients of Chinese medicines have shown that many of them suffer from poor water-solubility, stability, and bioavailability, which has severely limited their further development. The advent of nanomedicine represents a novel direction and paradigm for addressing these challenges.

Tailored Borneol-Modified Lipid Nanoparticles Nasal Spray for Enhanced Nose-to-Brain Delivery to Central Nervous System Diseases.

The nanodrug delivery system-based nasal spray (NDDS-NS) can bypass the blood-brain barrier and deliver drugs directly to the brain, offering unparalleled advantages in the treatment of central nervous system (CNS) diseases. However, the current design of NNDS-NS is excessively focused on mucosal absorption while neglecting the impact of nasal deposition on nose-to-brain drug delivery, resulting in an unsatisfactory nose-to-brain delivery efficiency. In this study, the effect of the dispersion medium viscosity on nasal drug deposition and nose-to-brain delivery in NDDS-NS was elucidated.

Fibroin nanodisruptor with Ferroptosis-Autophagy synergism is potent for lung cancer treatment.

Chemotherapy agents for lung cancer often cause apoptotic resistance in cells, leading to suboptimal therapeutic outcomes. FIN56 can be a potential treatment for lung cancer as it induces non-apoptotic cell death, namely ferroptosis. However, a bottleneck exists in FIN56-induced ferroptosis treatment; specifically, FIN56 fails to induce sufficient oxidative stress and may even trigger the defense system against ferroptosis, resulting in poor therapeutic efficacy.

Mechanisms and therapeutic targets of ferroptosis: Implications for nanomedicine design.

Ferroptosis is a nonapoptotic form of cell death and differs considerably from the well-known forms of cell death in terms of cell morphology, genetics, and biochemistry. The three primary pathways for cell ferroptosis are system Xc/glutathione peroxidase 4 (GPX4), lipid metabolism, and ferric metabolism. Since the discovery of ferroptosis, mounting evidence has revealed its critical regulatory role in several diseases, especially as a novel potential target for cancer therapy, thereby attracting increasing attention in the fields of tumor biology and anti-tumor therapy.

State-of-the-art strategies to enhance the mechanical properties of microneedles.

Microneedles (MNs) have gained increasing attention in the biomedical field, owing to their notable advantages over injectable and transdermal preparations. The mechanical properties of MNs are the key to determine whether MNs can puncture the skin for efficient drug delivery and therapeutic purposes. However, there is still lacking of a systemic summary on how to improve the mechanical properties of MNs.

Biomaterials-assisted cancer vaccine delivery: preclinical landscape, challenges, and opportunities.

Introduction: Cancer vaccines (protein and peptide, DNA, mRNA, and tumor cell) have achieved remarkable success in the treatment of cancer. In particular, advances in the design and manufacture of biomaterials have made it possible to control the presentation and delivery of vaccine components to immune cells.

Areas Covered: This review summarizes findings from major databases, including PubMed, Scopus, and Web of Science, focusing on articles published between 2005 and 2024 that discuss biomaterials in cancer vaccine delivery.

Biological Fate Tracking of Nitric Oxide-Propelled Microneedle Delivery System Using an Aggregation-Caused Quenching Probe.

Nanoparticle-loaded dissolving microneedles (DMNs) have attracted increasing attention due to their ability to provide high drug loading, adjustable drug release behavior, and enhanced therapeutic efficiency. However, such delivery systems still face unsatisfied drug delivery efficiency due to insufficient driving force to promote nanoparticle penetration and the lack of fate studies to guide formulation design. Herein, an aggregation-caused quenching (ACQ) probe (P4) was encapsulated in l-arginine (l-Arg)-based nanomicelles, which was further formulated into nitric oxide (NO)-propelled nanomicelle-integrated DMNs (P4/l-Arg NMs@DMNs) to investigate their biological fate.

"All-in-one" metal polyphenol network nanocapsules integrated microneedle patches for lipophagy fueled ferroptosis-mediated multimodal therapy.

Ferroptosis-mediated multimodal therapy has emerged as a promising strategy for tumor elimination, with lipid peroxide (LPO) playing a pivotal role. However, the therapeutic efficiency is limited due to insufficient intracellular levels of free fatty acids (FFA), which severely hinder the production of LPO. To address this limitation, we proposed a lipophagy strategy aimed at degrading lipid droplets (LDs) to release FFA, serving as the essential "fuel" for LPO production.

Imidazole-Rich, Four-Armed Host-Defense Peptidomimetics as Promising Narrow-Spectrum Antibacterial Agents and Adjuvants against Pseudomonas Aeruginosa Infections.

The development of narrow-spectrum antimicrobial agents is paramount for swiftly eradicating pathogenic bacteria, mitigating the onset of drug resistance, and preserving the homeostasis of bacterial microbiota in tissues. Owing to the limited affinity between the hydrophobic lipid bilayer interior of bacterial cells and most hydrophilic, polar peptides, the construction of a distinctive class of four-armed host-defense peptides/peptidomimetics (HDPs) is proposed with enhanced specificity and membrane perturbation capability against Pseudomonas aeruginosa by incorporating imidazole groups. These groups demonstrate substantial affinity for unsaturated phospholipids, which are predominantly expressed in the cell membrane of P.

Spatiotemporal fate of nanocarriers-embedded dissolving microneedles: the impact of needle dissolving rate.

Objective: Dissolving microneedles (DMNs) have shown great potential for transdermal drug delivery due to their excellent skin-penetrating ability and combination with nanocarriers (NCs) can realize targeted drug delivery. The objective of this study was to investigate the impact of microneedle dissolving rate on the in vivo fate of NC-loaded DMNs, which would facilitate the clinical translation of such systems.

Methods: Solid lipid nanoparticles (SLNs) were selected as the model NC for loading in DMNs, which were labeled by P4 probes with aggregation-quenching properties.

Photodynamic therapy for cancer: mechanisms, photosensitizers, nanocarriers, and clinical studies.

Photodynamic therapy (PDT) is a temporally and spatially precisely controllable, noninvasive, and potentially highly efficient method of phototherapy. The three components of PDT primarily include photosensitizers, oxygen, and light. PDT employs specific wavelengths of light to active photosensitizers at the tumor site, generating reactive oxygen species that are fatal to tumor cells.

Targeted treatment for biofilm-based infections using PEGylated tobramycin.

Chronic infections often involve biofilm-based bacteria, in which the biofilm results in significant resistance against antimicrobial agents and prevents eradication of the infection. The physicochemical barrier presented by the biofilm matrix is a major impediment to the delivery of many antibiotics. Previously, PEGylation has been shown to improve antibiotic penetration into biofilms in vitro.

Looking back, moving forward: protein corona of lipid nanoparticles.

Lipid nanoparticles (LNPs) are commonly employed for drug delivery owing to their considerable drug-loading capacity, low toxicity, and excellent biocompatibility. Nevertheless, the formation of protein corona (PC) on their surfaces significantly influences the drug's fate (such as absorption, distribution, metabolism, and elimination) upon administration. PC denotes the phenomenon wherein one or multiple strata of proteins adhere to the external interface of nanoparticles (NPs) or microparticles within the biological milieu, encompassing fluids (, serum-containing culture media) and fluids (such as blood and tissue fluids).

Epsilon-poly-l-lysine microneedle patch loaded with amorphous doxycycline nanoparticles for synergistic treatment of skin infection.

The development of antibiotic-loaded microneedles has been hindered for years by limited excipient options, restricted drug-loading space, poor microneedle formability, and short-term drug retention. Therefore, this study proposes a dissolving microneedle fabricated from the host-defense peptide ε-poly-l-lysine (EPL) as an antibacterial adjuvant system for delivering antibiotics. EPL serves not only as a major matrix material for the microneedle tips, but also as a broad-spectrum antibacterial agent that facilitates the intracellular accumulation of the antibiotic doxycycline (DOX) by increasing bacterial cell membrane permeability.

Overcoming the Low-Stability Bottleneck in the Clinical Translation of Liposomal Pressurized Metered-Dose Inhalers: A Shell Stabilization Strategy Inspired by Biomineralization.

Currently, several types of inhalable liposomes have been developed. Among them, liposomal pressurized metered-dose inhalers (pMDIs) have gained much attention due to their cost-effectiveness, patient compliance, and accurate dosages. However, the clinical application of liposomal pMDIs has been hindered by the low stability, i.

TRIM52 knockdown inhibits proliferation, inflammatory responses and oxidative stress in IL-1β-induced synovial fibroblasts to alleviate temporomandibular joint osteoarthritis.

To explore the mechanism of tripartite motif 52 (TRIM52) in the progression of temporomandibular joint osteoarthritis (TMJOA). Gene and protein expression were tested by quantitative real-time polymerase chain reaction and western blot, respectively. The levels of pro-inflammatory cytokines and oxidative stress factors were evaluated using enzyme-linked immunosorbent assay and biochemical kit, respectively.

The Necessity to Investigate In Vivo Fate of Nanoparticle-Loaded Dissolving Microneedles.

Transdermal drug delivery systems are rapidly gaining prominence and have found widespread application in the treatment of numerous diseases. However, they encounter the challenge of a low transdermal absorption rate. Microneedles can overcome the stratum corneum barrier to enhance the transdermal absorption rate.