Iontophoresis-Integrated Smart Microneedle Delivery Platform for Efficient Transdermal Delivery and On-Demand Insulin Release.

Transdermal insulin delivery in a painless, convenient, and on-demand way remains a long-standing challenge. A variety of smart microneedles (MNs) fabricated by glucose-responsive phenylboronic acid hydrogels have been previously developed to provide painless and autonomous insulin release in response to a glucose level change. However, like the majority of MNs, their transdermal delivery efficiency was still relatively low compared to that with subcutaneous injection.

Prediction of toxicity and identification of key components for complex mixtures containing hormetic components.

Mixtures containing hormetic components are likely to induce hormesis. However, due to the presence of stimulatory effects, predicting the toxicity of such mixtures and identifying their key components face challenges. This study investigated the complex relationship between the stimulatory effects of individual components and their mixtures, focusing on predicting mixture toxicity and identifying key components influencing this toxicity.

Correction: Multiple pH responsive zwitterionic micelles for stealth delivery of anticancer drugs.

[This corrects the article DOI: 10.1039/C6RA11645K.].

Self-assembling chitosan based injectable and expandable sponge with antimicrobial property for hemostasis and wound healing.

Chitosan and chitosan derivative are widely used in hemostasis, antibiosis and wound repair for its good biocompatibility and unique effect. However, the preparation of chitosan based hemostatic materials or wound dressings generally involves chemical crosslinking agent introduction, acid residue or complicated preparation process, which limits its clinical application. In this study, an injectable and expandable chitosan sponge was constructed by chitosan (CS) and quaternized chitosan (QCS) self-assembly without acid retention and chemical crosslinker introduction.

pH and glucose dual-responsive phenylboronic acid hydrogels for smart insulin delivery.

Phenylboronic acid (PBA) is a widely exploited glucose-sensitive element for constructing glucose-responsive hydrogels to enable smart insulin delivery. However, its relatively high intrinsic p affects its binding with glucose under physiological conditions and thus limits its application. Herein, we developed a series of boronate-containing PLP-PBA polymers by conjugating glucose-sensitive 3-aminophenylboronic acid (3-PBA) onto the backbone of a metabolite-derived, pH-responsive poly-L-lysine isophthalamide (PLP) polymer with a p value of 4.

An innovative mixture sampling strategy with uniform design: Application to global sensitivity analysis of mixture toxicity.

Global sensitivity analysis combined with quantitative high-throughput screening (GSA-qHTS) uses random starting points of the trajectories in mixture design, which may lead to potential contingency and a lack of representativeness. Moreover, a scenario in which all factor levels were at stimulatory effects was not considered, thereby hindering a comprehensive understanding of GSA-qHTS. Accordingly, this study innovatively introduced an optimised experimental design, uniform design (UD), to generate non-random and representative sample points with smaller uniformity deviation as starting points of multiple trajectories.

Light-driven rGO/CuO tubular nanomotor with active targeted drug delivery for combination treatment of cancer cells.

The unprecedented navigation ability in micro/nanoscale and tailored functionality tunes micro/nanomotors as new target drug delivery systems, open up new horizons for biomedical applications. Herein, we designed a light-driven rGO/CuO tubular nanomotor for active targeting of cancer cells as a drug delivery system. The propulsion performance is greatly enhanced in real cell media (5% glucose cells isotonic solution), attributing to the introduction of oxygen vacancy and reduced graphene oxide (rGO) layer for separating photo-induced electron-hole pairs.

Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy.

Despite the great potential of anti-PD-L1 antibodies for immunotherapy, their low response rate due to an immunosuppressive tumor microenvironment has hampered their application. To address this issue, we constructed a cell membrane-coated nanosystem (mB4S) to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor effect. In this system, Epirubicin (EPI) as an immunogenic cell death (ICD) inducer was coupled to a branched glycopolymer hydrazone bonds and diABZI as a stimulator of interferon genes (STING) agonist was encapsulated into mB4S.

Triune Nanomodulator Enables Exhausted Cytotoxic T Lymphocyte Rejuvenation for Cancer Epigenetic Immunotherapy.

Oncogene activation and epigenome dysregulation drive tumor initiation and progression, contributing to tumor immune evasion and compromising the clinical response to immunotherapy. Epigenetic immunotherapy represents a promising paradigm in conquering cancer immunosuppression, whereas few relevant drug combination and delivery strategies emerge in the clinic. This study presents a well-designed triune nanomodulator, termed ROCA, which demonstrates robust capabilities in tumor epigenetic modulation and immune microenvironment reprogramming for cancer epigenetic immunotherapy.

Time-dependent nonmonotonic concentration-response and synergism of alkyl glycosides with different alkyl side chain to Vibrio qinghaiensis sp. -Q67.

Alkyl glycosides (AGs), commonly used nonionic surfactants, may have toxic effects on the environmental organisms. However, the complex concentration-response patterns of AGs with varying alkyl side chains and their mixtures have not been thoroughly studied. Therefore, the luminescence inhibition toxicities of six AGs with different alkyl side chains, namely, ethyl (AG02), butyl (AG04), hexyl (AG06), octyl (AG08), decyl (AG10), and dodecyl (AG12) glucosides, were determined in Vibrio qinghaiensis sp.

Time-dependent hormesis transfer from five high-frequency personal care product components to mixtures.

There is potential for personal care products (PCPs) components and mixtures to induce hormesis. How hormesis is related to time and transmitted from components to mixtures are not clear. In this paper, we conducted determination of components in 16 PCP products and then ran frequent itemset mining on the component data.

Mitocytosis Mediated by an Enzyme-Activable Mitochondrion-Disturbing Polymer-Drug Conjugate Enhances Active Penetration in Glioblastoma Therapy.

The application of nanomedicines for glioblastoma (GBM) therapy is hampered by the blood-brain barrier (BBB) and the dense glioblastoma tissue. To achieve efficient BBB crossing and deep GBM penetration, this work demonstrates a strategy of active transcellular transport of a mitochondrion-disturbing nanomedicine, pGBEMA-b-pSSPPT (GBEPPT), in the GBM tissue through mitocytosis. GBEPPT is computer-aided designed and prepared by self-assembling a conjugate of an amphiphilic block polymer and a drug podophyllotoxin (PPT).

NIR-Mediated CuO/Au Nanomotors for Synergistically Treating Hepatoma Carcinoma Cells.

We presented a NIR-driven Janus CuO/Au nanomotor. The nanomotor has a truncated octahedral structure. By asymmetric Au evaporation, the light response range of CuO nanomotor is extended to near-infrared range, and the speed of CuO/Au nanomotors under NIR is significantly increased.

Homomultivalent Polymeric Nanotraps Disturb Lipid Metabolism Homeostasis and Tune Pyroptosis in Cancer.

Genetic manipulations and pharmaceutical interventions to disturb lipid metabolism homeostasis have emerged as an attractive approach for the management of cancer. However, the research on the utilization of bioactive materials to modulate lipid metabolism homeostasis remains constrained. In this study, heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin (TMCD) is utilized to fabricate homomultivalent polymeric nanotraps, and surprisingly, its unprecedented ability to perturb lipid metabolism homeostasis and induce pyroptosis in tumor cells is found.

Unraveling Ros Conversion Through Enhanced Enzyme-Like Activity with Copper-Doped Cerium Oxide for Tumor Nanocatalytic Therapy.

Nanozyme catalytic therapy for cancer treatments has become one of the heated topics, and the therapeutic efficacy is highly correlated with their catalytic efficiency. In this work, three copper-doped CeO supports with various structures as well as crystal facets are developed to realize dual enzyme-mimic catalytic activities, that is superoxide dismutase (SOD) to reduce superoxide radicals to H O and peroxidase (POD) to transform H O to ∙OH. The wire-shaped CeO /Cu-W has the richest surface oxygen vacancies, and a low level of oxygen vacancy (Vo) formation energy, which allows for the elimination of intracellular reactive oxygen spieces (ROS) and continuous transformation to ∙OH with cascade reaction.

Co-assembly of polymeric conjugates sensitizes neoadjuvant chemotherapy of triple-negative breast cancer with reduced systemic toxicity.

Rational design of polymeric conjugates could greatly potentiate the combination therapy of solid tumors. In this study, we designed and prepared two polymeric conjugates (HT-DTX and PEG-YC-1), whereas the drugs were attached to the PEG via a linker sensitive to cathepsin B, over-expressed in TNBC. Stable nanostructures were formed by these two polymer prodrug conjugates co-assembly (PPCC).

Customizing biomimetic surface attributes of dendritic lipopeptide nanoplatforms for extended circulation.

The pressing demand for innovative approaches to create delivery systems with heightened drug loading and prolonged circulation has spurred numerous efforts, yielding some successes but accompanied by constraints. Our study proposes employing dendritic lipopeptide with precisely balanced opposing charges to extend blood residency for biomimetic nanoplatforms. Neutrally mixed-charged zwitterionic nanoparticles (NNPs) achieved a notable 19 % simvastatin loading content and kept stable even after one-month storage at 4 °C.

Nature-Inspired Scarless Healing: Guiding Biomaterials Design for Advanced Therapies.

The use of biomaterials in the treatment of skin wounds has been steadily increasing over the last two decades. The key to the successful application of biomaterials in scar reduction is the up-to-date knowledge of the actors involved in accelerated healing and the cellular factors that can be implemented in bioinspired materials. Natural models of scarless healing such as oral mucosa, fetal skin and the skin of amphibians, fish, and reptiles are a great source of information.

Nanomedicine Combats Drug Resistance in Lung Cancer.

Lung cancer is the second most prevalent cancer and the leading cause of cancer-related death worldwide. Surgery, chemotherapy, molecular targeted therapy, immunotherapy, and radiotherapy are currently available as treatment methods. However, drug resistance is a significant factor in the failure of lung cancer treatments.

Enhancing drug penetration in solid tumors via nanomedicine: Evaluation models, strategies and perspectives.

Effective tumor treatment depends on optimizing drug penetration and accumulation in tumor tissue while minimizing systemic toxicity. Nanomedicine has emerged as a key solution that addresses the rapid clearance of free drugs, but achieving deep drug penetration into solid tumors remains elusive. This review discusses various strategies to enhance drug penetration, including manipulation of the tumor microenvironment, exploitation of both external and internal stimuli, pioneering nanocarrier surface engineering, and development of innovative tactics for active tumor penetration.

Stimuli-activatable nanomedicine meets cancer theranostics.

Stimuli-activatable strategies prevail in the design of nanomedicine for cancer theranostics. Upon exposure to endogenous/exogenous stimuli, the stimuli-activatable nanomedicine could be self-assembled, disassembled, or functionally activated to improve its biosafety and diagnostic/therapeutic potency. A myriad of tumor-specific features, including a low pH, a high redox level, and overexpressed enzymes, along with exogenous physical stimulation sources (light, ultrasound, magnet, and radiation) have been considered for the design of stimuli-activatable nano-medicinal products.