Drug Loading Capability Research Articles

Recently emerging advancements in polymeric nanogel nanoarchitectures for drug delivery applications

The advancement from hydrogel (HDG) to nanogel (NAG) was a remarkable transition in the field of drug delivery (DD). This breakthrough opened a vista of feasibilities for the gel to interact at the cellular spectrum and prospects for systemic administering. The formation of NAG improved stimuli sensitivity and stability while suppressing the propensity to swelling. NAGs are fabricated with varying architectures including core-shell nanoparticulates, hollow NAG, dual walled as well as yolkish shell architectures, and exhibit high prospects as advanced drug delivery systems (DDS), which is ascribed to their inherent multifunctionalities along with stability in biologically affiliated fluids. Thus, due to their inherent nanosize, NAGs can penetrate replacement tissues, unlike bigger HDGs, while simultaneously proffering elevated drug loading capability as well as encapsulation effectiveness attributed to their inherent swelling capability. Here, a comprehensive elucidation of the synthesization, nanotechnological advancements, and broad research investigations conducted recently are presented. The functions of utilizing NAG as a successful tool in biomedicals, environmental protection, smart gadgets, cell cultures, and so on, are also elucidated. Therefore, this paper presents very recently emerging trends in drug releasing capability of polymeric nanogel nanoarchitectures, with special highlight on NAG mechanisms of drug releasing, triggering-sensitive NAGs, and elucidation of varying schemes for NAG releasing profiles.

Preparation, Characterization of Bacterial Cellulose and Chlordiazepoxide Tablets for Oral Drug Delivery

Bacterial cellulose (BC) is a highly purified form of cellulose that offers several benefits, including an ultrafine fiber network, a high water retention capacity, and simple fabrication into desired forms. There has been a recent uptick in BC’s focus on drug delivery for biomedical applications. Studies on prodrug design, controlled-release methods, and pill coating have all been conducted for BC. This research was done to determine if BC might be employed as a medication carrier in chemical and biological formulations. BC microparticles laden with the medication were produced via grinding. Clordiazepoxide hydrochloride (CDP) was used to test the microparticles’ drug loading and release capabilities. Particle morphologies, drug loading efficiency, loaded drug physical state, and drug release behavior were all assessed for the manufactured microparticles. Amorphous microparticles were formed from BC microparticles. An scanning electron microscope (SEM) study found that the microparticles had a nearly round form with an average diameter of 400–500 μm. Drug loading was greater in the renewed BC microparticles (37.57 ± 0.22%) when the concentration of drugs was held constant at 10%. More than 85% of the medication was delivered for all formulations in the first 30 minutes.

Bioinspired poly(cation-π) micelles drug delivery platform for improving chemotherapy efficacy.

Cation-π interactions widely exist in biological systems and play important roles in driving the self-assembly of biological molecules, stabilizing protein structures, and mediating molecular recognitions. Herein, a novel bioinspired poly(cation-π) micelles drug delivery platform is designed and constructed, based on the block copolymers with random cationic-aromatic sequences (amphiphilic cation-π polymer). Compared to the polymeric micelles formed by conventional amphiphilic block copolymers which are commonly limited to hydrophobic drugs loading, the engineered poly(cation-π) micelles can serve as a universal nanocarrier for a wide variety of hydrophobic and hydrophilic drugs with π-structure. It is found that due to the strong cation-π interactions integrated in the core of poly(cation-π) micelles, this nanosystem performs improved structural stability and higher drug loading capability. Especially, in the oxidation-responsive poly(cation-π) micelles as proof-of-concept, the process of stimuli-induced drug release is found significantly accelerated under the biologically relevant level of H2O2 in tumor microenvironment. Furthermore, the mechanism of cation-π interaction enhanced H2O2-sensitivity of poly(cation-π) micelles is proposed, and the improving anti-tumor efficacy is demonstrated in both in vitro and in vivo models. This work broadens the construction strategy of polymeric micelles and offers a universal drug delivery platform for efficient tumor chemotherapy.

Biogenic polymer-encapsulated diosgenin nanoparticles: Biodistribution, pharmacokinetics, cellular internalization, and anticancer potential in breast cancer cells and tumor xenograft

Diosgenin (DGN) is a natural bioactive steroidal saponin from therapeutic herbs and it exhibits potential anticancer efficacy. Here, we report the preparation of poly lactide-co-glycolide (PLGA)-encapsulated diosgenin nanoparticles (PLGA-DGN NPs) and characterization of their physicochemical nature, and morphology as well as inspect their drug-loading capability, in vitro drug release, pharmacokinetics, bio-distribution, safety profile. The in vitro and in vivo antineoplastic activities of PLGA-DGN NPs were also examined against the MCF-7 breast cancer cell line and in the Ehrlich ascites carcinoma (EAC) tumor xenograft model, respectively. The results displayed an appropriate size (∼147 nm), spherical shape, and a narrow polydispersity index. The nanoparticles showed a high encapsulation efficacy (78%), loading capacity (8%), good colloidal stability, and an initial burst release at an acidic medium. The nanoparticles exhibited significant cytotoxic activity at their IC50 dose compared to diosgenin. PLGA-DGN NPs facilitated cellular internalization of DGN in human breast cancer MCF-7 cells and extended the blood circulation time showing an excellent pharmacokinetic profile. Bio-distribution study revealed that PLGA-DGN NPs could significantly enhance DGN accumulation in tumor tissue. The safety profile of the PLGA-DGN NPs was confirmed in histopathologic, hematologic, and immunologic parameters of Swiss albino mice. At the same time, an effective antiangiogenic, and antiproliferative potential of PLGA-DGN NPs were exhibited in mice tumor xenograft model by showing tumor regression and down-regulating CD31 and Ki-67 expression. Therefore, PLGA-DGN NPs could be utilized as a promising anticancer drug, opening up a new avenue for further research.

Self-assembled Natural Product-based Carrier-free Nanoplatforms for Efficient Bioactivity

Natural products featured by an abundant molecule skeleton and structural complexity exhibit extensive pharmacological or biological activities. Thus, natural active ingredients are an important source of drug research and development. However, the inherent defects, including low solubility, low bioavailability, and unacceptable off-target toxicity, affect their development into clinical drugs. Recently, carrier-free supermolecule nanodrugs have attracted considerable attention. These nanodrugs are self-assembled by pure drugs mainly through hydrophobicity, hydrogen bond, π-π stacking, and electrostatic interaction, which possess a high drug loading capability, enhanced water solubility of the drugs, and synergistic therapeutic efficacy. In this review, natural product-based carrier-free nanoplatforms with self-assembly for efficient bioactivity were examined. These self-assembled natural products included triterpenoids, alkaloids, flavonoids, and anthraquinones. Moreover, the morphology of the formed nanoplatforms could be a nanosphere, nanofiber, nanorod, or fibrillar network, and they could exhibit several bioactivities, such as antitumor, anti-inflammatory, immunoregulation, and liver protection. Briefly, we analyzed the types and sources, formation mechanism, biological activity, and mode of action of the nanomedicine, and discussed the future of this field. We believe this review would provide a landscape of natural product-based carrier-free nanoplatforms.

RuNO-Thnl-loaded nanoplatform excited by 808 nm near-infrared light for gas release

Förster energy resonance transfer (FRET) refers to a type of non-radiative energy transfer between two chromophores. In addition to the distance between the donor and acceptor, it depends on the extent of overlap between the fluorescence spectrum of the donor and the absorption spectrum of the acceptor. Based on the principle of FRET, in this study, NIR-responsive nanoplatforms comprising up-conversion nanoparticles (UCNPs)@mSiO2&RuNO-Thnl were designed for the targeted and controllable release of NO. First, core–shell UCNPs were prepared by the thermal decomposition method and then coated with a mesoporous silica layer by surface modification. The prepared UCNPs@mSiO2 was excited by NIR at 808 nm, which avoided the overheating of Yb3+ and increased the penetration depth; in addition, it imparted drug-loading capability and biocompatibility to the UCNPs. Subsequently, RuNO-Thnl and UCNP@mSiO2 were combined using van der Waals forces. Furthermore, UCNPs@mSiO2 converted 808 nm NIR laser irradiation into ultraviolet light or visible light, thereby exciting RuNO-Thnl for the effective local release of NO. The results showed that this NO release platform can release 0.0012–0.0037 μmol/mL of NO gas when the concentration of the solution containing the nanoplatform is in the range of 0.15–0.8 mg/mL, allowing for concentration-controlled NO release on demand. Importantly, the temperature changes generated during the conversion process were not harmful to cells and tissues. This targeted and controlled release approach has broad application prospects in NO-based medical therapy.

Dissolving microneedles: Applications and growing therapeutic potential.

Microneedles are a rapidly developing method for the transdermal delivery of therapeutic compounds. All types of microneedles, whether solid, hollow, coated, or dissolving function by penetrating the stratum corneum layer of the skin producing a microchannel through which therapeutic agents may be delivered. To date, coated and hollow microneedles have been the most successful, despite suffering from issues such as poor drug loading capabilities and blocked pores. Dissolving microneedles, on the other hand, have superior drug loading as well as other positive attributes that make it an ideal delivery system, including simple methods of fabrication and disposal, and abundantly available materials. Indeed, dissolvable microneedles can even be fabricated entirely from the therapeutic agent itself thus eliminating the requirement for additional excipients. This focused review presents the recent developments and trends of dissolving microneedles as well as potential future directions. The advantages, and disadvantages of dissolving microneedles as well as fabrication materials and methods are discussed. The potential applications of dissolving microneedles as a drug delivery system in different therapeutic areas in both research literature and clinical trials is highlighted. Applications including the delivery of cosmetics, vaccine delivery, diagnosis and monitoring, cancer, pain and inflammation, diabetes, hair and scalp disorders and inflammatory skin diseases are presented. The current trends observed in the microneedle landscape with particular emphasis on contemporary clinical trials and commercial successes as well as barriers impeding microneedle development and commercialisation are also discussed.

Modified gelatin/iron- based metal-organic framework nanocomposite hydrogel as wound dressing: Synthesis, antibacterial activity, and Camellia sinensis release

A new kind of Camellia sinensis-loaded nanocomposite hydrogel based on modified gelatin/iron-metal-organic framework was developed as an antibacterial wound dressing. Gelatin as a biocompatible natural polymer was modified with methacrylate anhydride to produce gelatin methacrylate. Thereafter, acrylic acid and acrylamide were grafted on gelatin methacrylate during an aqueous polymerization process. To enhance the porosity, mechanical strength, and drug loading capability of the hydrogel and reduce its toxicity, iron- based metal-organic framework was incorporated within the hydrogel. To add more functionality to the final wound dressing, Camellia sinensis, an antibacterial herbal drug was loaded on the hydrogel. The structural and chemical properties of prepared nanocomposite hydrogel were investigated by FTIR, XRD, SEM, and TGA techniques. The incorporation of iron-based metal-organic framework within the hydrogel matrix led to an increase in its water absorption value from 400.10 to 547.96 (g/g). The release study of Camellia sinensis (CS) extract from the prepared nanocomposite hydrogel exhibited a sustained release manner. The antibacterial test revealed the nanocomposite hydrogel contain extract has an effective antibacterial function against "Bacillus serous", "Staphylococcus aureus", "Streptococcus mutans"," Escherichia coli", "Klebsiella pneumoniae", and "Pseudomonas aeruginosa" bacteria. Therefore, the synthesized nanocomposite is a good candidate as an antibacterial hydrogel wound dressing..

Conductive Microneedle Patch with Electricity-Triggered Drug Release Performance for Atopic Dermatitis Treatment.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that seriously affects the life quality of patients. Topical administration of glucocorticoids is considered to be the most effective anti-inflammatory treatment. However, due to the barrier function of skin, only less than 20% of topical drug molecules could diffuse into the skin. Therefore, it is of great importance to develop an effective strategy to improve AD therapy. In this study, we reported a two-electrode microneedle patch (t-EMNP) composed of a polylactic acid-platinum (PLA-Pt) MN array and polylactic acid-platinum-polypyrrole (PLA-Pt-PPy) MN array for improving the transdermal drug delivery efficacy. The drug loading capability of MNs could be altered by employing different polymerization times and drug concentrations. The drug release rate of MNs could be changed by applying different voltages. We further developed a controlled transdermal drug delivery system (c-TDDS) based on this two-electrode microneedle patch (t-EMNP), exhibiting the remarkable performance of the electricity-triggered drug release profile. The drugs could be released with electrical stimulation, while there was almost no drug release without electrical stimulation. For AD treatment in vivo, this MN patch with electricity-triggered drug release performance could effectively deliver more drugs into the skin compared with other controls such as dexamethasone cream, which efficiently alleviate AD. In sum, this work not only developed a smart patch for improving AD treatment but also provided a promising approach of transdermal drug delivery on demand.

New Peptide Functionalized Nanostructured Lipid Carriers with CNS Drugs and Evaluation Anti-proliferative Activity.

Nanoparticulate systems have been widely investigated as delivery vectors for efficient drug delivery in different diseases. Nanostructured lipid carriers (NLC) are composed of both solid and liquid lipids (glyceryl dibehenate and diethylene glycol monoethyl ether) and have demonstrated enhanced biological compatibility and increased drug loading capability. Furthermore, the use of peptides, in particular cell-penetrating peptides, to functionalize nanoparticles and enhance cell membrane permeation was explored in this paper. In this paper, we described the synthesis of a new conjugated of tranylcypromine with MAP. In addition, taking into consideration our previous results, this study developed different NLCs loaded with three central nervous system (CNS) drugs (tacrine (TAC), rasagiline (RAS), and tranylcypromine (TCP)) functionalized with model amphipathic peptide (MAP) and evaluated their activity against cancer cells. Particle size analysis demonstrated NLC presented less than 200 nm and a polydispersity index less than 0.3. Moreover, in vitro results showed that conjugation of MAP with drugs led to a higher decrease in cell viability of a neuroblastoma cell line and Caco-2 cell line, more than MAP alone. Furthermore, NLC encapsulation contributed to higher cellular delivery and enhanced toxic activity at lower concentrations when compared with free or co-administration drug-MAP conjugate.

Toward understanding the kinetics of disassembly of ferritins of varying origin and subunit composition

Understanding the reversible reassembly properties of ferritins (FRTs) is crucial for enabling their applicability in nanomedicine. These properties include drug loading capabilities and also subsequent payload release in desired site-of-action. Thus, the presented study is focused on understanding the disassembly of recombinantly produced FRTs of varying origin and subunit composition, i.e. equine FRT composed of 22 L- and 2 H-subunits (EcaLH) or 24 L-subunits (EcaL), human FRT composed of 24 H-subunits (HsaH) and archaeal Pyrococcus furiosus FRT (Pfu). Disassembly was distinctly influenced by pH and ionic strength. Except for Pfu, the disassembly kinetics in acidic pH is rapid upon reaching an innate threshold, reaching the final state within minutes. Disassembly kinetics in basic pH is slower. Pfu is partially disassembled within the entire pH range. While equine FRT disassembles into free subunits, HsaH disassembles into subunit clusters. EcaL and Pfu form large aggregates during disassembly in mildly acidic pH, although basic pH causes partial disassembly without aggregation, suggesting usability for basic pH-triggered drug loading. We show that in human serum/plasma, FRTs readily form protein corona, hampering their uptake. Interestingly, we found out that archaeal Pfu likely exhibits similar receptor affinity as mammalian FRTs. Further, in vivo toxicity and biodistribution study of a single dose of FRTs demonstrated very low toxicity of FRTs and their preferential liver/kidney bioaccumulation.

Dopamine-triggered one-step functionalization of hollow silica nanospheres for simultaneous lubrication and drug release

Osteoarthritis (OA) has been regarded as a lubrication deficiency related joint disease. Combination of both joint lubrication and drug intervention may provide a promising nonsurgical strategy for treatment of OA. Developing novel and simple approaches to fabricate superlubricating nanoparticles with drug release property is highly required. Herein, dopamine triggered one-step polymerization method was employed to fabricate polydopamine/poly(3-sulfopropyl methacrylate potassium salt) (PDA—PSPMA) conjugate coating on hollow silica (h-SiO2) nanosphere surfaces to engineer functional nanoparticles (h-SiO2/PDA—PSPMA). The as-prepared h-SiO2/PDA—PSPMA exhibits excellent aqueous lubrication performance on biomaterial substrates as well as natural bovine articular cartilage based on hydration effect of negatively charged PDA—PSPMA coating and “rolling” effect of h-SiO2 nanospheres. In vitro drug loading-release experiments demonstrate that PDA—PSPMA coating functionalized h-SiO2 nanospheres show high drug-loading and sustained-release capability of an anti-inflammatory drug, diclofenac sodium (DS). Such h-SiO2/PDA—PSPMA nanospheres can be potentially used as a synergistic therapy agent for OA treatment combining by simultaneous joint lubrication and drug release.

Mussel-inspired collagen-hyaluronic acid composite scaffold with excellent antioxidant properties and sustained release of a growth factor for enhancing diabetic wound healing.

Long-term non-healing diabetic wounds are always a serious challenge and a global healthcare burden that needs to be resolved urgently in the clinic. Prolonged inflammation and impaired angiogenesis are the main direct causes of diabetic wounds. With the development of polymer biomaterials, various wound dressings have been created, but a few of them have been applied to the clinical management of diabetic wounds. Here, we developed a mussel-inspired bioactive scaffold consisting mainly of collagen and hyaluronic acid, which are natural biopolymer materials contained in human tissues. First, we fabricated different polydopamine modified lyophilized collagen hyaluronic acid scaffolds under different concentrations of dopamine alkaline solutions, 0.5, 1, 2 ​mg/mL, so named CHS-PDA-0.5, CHS-PDA-1, CHS-PDA-2. After testing their physical and chemical properties, antioxidant effect, inflammation regulation, as well as drug loading and release capabilities, we obtained a bioactive endothelial growth factor (EGF)-loaded wound dressing, CHS-PDA-2@EGF, which can resist reactive oxygen species (ROS) and promote the regeneration of chronic wounds in diabetic rats by reducing inflammation. In addition, the scaffold showed excellent swelling ability, a certain coagulation effect and reasonable degradation. Therefore, the scaffold has great potential to be used in clinical diabetic wound treatment as a low-cost and easily available wound dressing to accelerate chronic wound healing.

Icaritin-loaded PLGA nanoparticles activate immunogenic cell death and facilitate tumor recruitment in mice with gastric cancer

This study aimed to explore the anti-tumor effect of icaritin loading poly (lactic-co-glycolic acid) nanoparticles (refer to PLGA@Icaritin NPs) on gastric cancer (GC) cells. Transmission Electron Microscope (TEM), size distribution, zeta potential, drug-loading capability, and other physicochemical characteristics of PLGA@Icaritin NPs were carried out. Furthermore, flow cytometry, confocal laser scanning microscope (CLSM), Cell Counting Kit-8 (CCK-8), Transwell, Elisa assay and Balb/c mice were applied to explore the cellular uptake, anti-proliferation, anti-metastasis, immune response activation effects, and related anti-tumor mechanism of PLGA@Icaritin NPs in vitro and in vivo. PLGA@Icaritin NPs showed spherical shape, with appropriate particle sizes and well drug loading and releasing capacities. Flow cytometry and CLSM results indicated that PLGA@Icaritin could efficiently enter into GC cells. CCK-8 proved that PLGA@Icaritin NPs dramatically suppressed cell growth, induced Lactic dehydrogenase (LDH) leakage, arrested more GC cells at G2 phase, and inhibited the invasion and metastasis of GC cells, compared to free icaritin. In addition, PLGA@Icaritin could help generate dozens of reactive oxygen species (ROS) within GC cells, following by significant mitochondrial membrane potentials (MMPs) loss and excessive production of oxidative-mitochondrial DNA (Ox-mitoDNA). Since that, Ox-mitoDNA further activated the releasing of damage associated molecular pattern molecules (DAMPs), and finally led to immunogenic cell death (ICD). Our in vivo data also elaborated that PLGA@Icaritin exerted a powerful inhibitory effect (∼80%), compared to free icaritin (∼60%). Most importantly, our results demonstrated that PLGA@Icaritin could activate the anti-tumor immunity via recruitment of infiltrating CD4+ cells, CD8+ T cells and increased secretion of cytokine immune factors, including interferon-γ (IFN-γ) tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1).++ Our findings validate that the successful design of PLGA@Icaritin, which can effectively active ICD and facilitate tumor recruitment in GC through inducing mitoDNA oxidative damage.

Tumor microenvironment–responsive versatile “Trojan horse” theranostic nanoplatform for magnetic resonance imaging–guided multimodal synergistic antitumor treatment

A natural killer (NK)-92 cell membrane-camouflaged mesoporous MnO2-enveloped Au@Pd (Au@Pd@MnO2) nanoparticles (denoted as APMN NPs)-based versatile biomimetic theranostic nanoplatform was developed for magnetic resonance (MR) imaging-guided multimodal synergistic antitumor treatments. In this core-shell nanostructure, an Au@Pd core induced near-infrared (NIR)-activatable hyperthermal effects and nanozyme catalytic activity, while a mesoporous MnO2 shell not only afforded a high drug-loading capability, tumor microenvironment (TME)-triggered MR imaging and drug release, but also endowed catalase-, glutathione peroxidase-, and Fenton-like activities. Furthermore, the NK-92 cell membrane camouflaging endowed the NPs with enhanced tumor-targeting capability, immune escape function, and membrane protein-mediated tumoral uptake property. The doxorubicin-loaded APMN (D-APMN) NPs exhibited TME-responsive drug release properties. Furthermore, the cellular uptake, in vivo MR imaging, and NIR thermal imaging confirmed the active tumor-targeting capability and TME-responsive MR imaging property of these biomimetic NPs. An antitumor efficacy test, histological analyses, and blood biochemical profiles suggested that the developed D-APMN NPs possessed a high antitumor activity and biosafety in tumor-bearing nude mice. Therefore, the developed APMN NPs held great potential as an intelligent and comprehensive theranostic nanoplatform for tumor-specific bioimaging and TME-responsive multimodality treatment based on photothermal therapy, chemodynamic therapy, and chemotherapy. Statement of significanceExploring intelligent and comprehensive theranostic nanoplatforms to integrate tumor-specific bioimaging and TME-responsive multimodal therapy effectively is a challenge. Herein, we successfully developed a new kind of NK-92 cell membrane-camouflaged mesoporous MnO2-enveloped Au@Pd nanoparticles (APMN NPs)-based versatile biomimetic theranostic nanoplatform for the potential MR imaging-guided multimodal synergistic antitumor treatments. These NPs could integrate unique structural, optical, multiple-catalytic, paramagnetic, and biological merits of NK-92 cell membrane, Au@Pd cores and mesoporous MnO2 shell in a single nanoplatform. The NK-92 cell membrane camouflaging endowed the NPs with enhanced tumor-targeting capability, immune escape function, and membrane protein–mediated tumoral uptake property. The new information obtained from this study may be beneficial to promote the development of novel TME-responsive versatile “Trojan horse” theranostic nanoplatforms for efficient MR imaging-guided multimodal synergistic treatment.

Achieving a “all in one” Fe/Tm-MOFs with controllable photothermal and catalytic performance for imaging-guided multi-modal synergetic therapy

Targeting excess H2O2 in the tumor microenvironment, nanotheranostic agents for catalytic therapy are designed based on Fenton reaction, catalyzing H2O2 into oxygen and hydroxyl radical (OH). But the catalytic efficiency in tumor microenvironment is not satisfactory. In order to solve the problem, a series of bimetallic-dual ligands metal-organic frameworks Fe/Tm-MOFs were designed, that Fe3+ and Tm3+ as metalions, 2-methylimidazole and trimesic acid as ligands. Due to the doped Tm3+ in Fe/Tm-MOFs and the conjugated structures formed by two ligands, the rate of electron transfer was improved, thus promoting the generation of OH at some extent. In addition, the photothermal effect of Fe/Tm-MOFs further promotes the generation of OH, which was evidenced by the 3,3′,5,5′-tetramethylbenzidine(TMB). Combining the drug loading and release capabilities of Fe/Tm-MOFs, synergetic therapy of photothermal/chemo-/catalytic therapy can be achieved. In vitro results reveal that DOX release behaviors are both pH- and thermal-responsive. In vivo anti-cancer results show that the tumors of mice almost disappeared within 10 days, which were injected with Fe/Tm-MOFs/DOX and irradiated with 808 nm for 10 min. Thus, an excellent therapeutic performance has been achieved. Besides, Fe/Tm-MOFs can serve as a multimodality bioimaging contrast agent, covering fluorescence imaging, photothermal imaging and magnetic resonance imaging. Thus, an all-in-one nanotheranostic agent is constructed, improving the catalytic efficiency and providing a novel method to design an efficient nanotheranostic agent.

Photothermal-responsive fiber dressing with enhanced antibacterial activity and cell manipulation towards promoting wound‐healing

For chronic persistent skin injuries, functional wound dressings with improved antibacterial action and cell control are extremely appealing. In this study, we design and fabricate a composite fiber dressing with near-infrared (NIR) laser-induced hyperthermia and transformable topographies that can protect the wound from bacterial infection while also encouraging cell recruitment and tissue regeneration. Polycaprolactone/gelatin (PCL/Gel) with melting point close to photothermal temperature were electrospun as the supporting matrix. The zeolitic imidazolate framework-8 (ZIF-8)-derived nanocarbon was synthesized as NIR laser-triggered nanoagent and then electrospun within oriented PCL/Gel fibers to enable the inorganic/polymer composite fiber dressing with photo-to-thermal conversion effect and drug loading capability. The composite fiber dressing exhibits excellent photothermal performance and stage-specific transformable topographies (photothermal-triggered melting behavior of oriented PCL/Gel fibers) after multiple laser irradiations, which can generate local massive heat and abundant drug release for synergistic sterilization, as well as direct cell migration and adhesion/spreading to promote tissue regeneration. Furthermore, in vivo testing demonstrates that the photothermal-responsive fiber dressing accelerates wound closure process by synergistically improving antibacterial and cell manipulation. Overall, this composite fiber dressing offers a promising integrated wound healing strategy.

Mesoporous porphyrinic metal-organic framework nanoparticles/3D nanofibrous scaffold as a versatile platform for bone tumor therapy

Removal of residual tumor cells and regeneration of large bone defects are urgently required after surgical resection of bone tumors. To address these issues, a bifunctional scaffold with high photothermal effect and osteogenesis was developed for bone tumor therapy. Sintered mesoporous imidazolate framework 8 (ZIF8) nanoparticles with porphyrin-like macrocycles were synthesized by calcination of ZIF8 precursors under an N2 atmosphere. The prepared ZIF8 possesses good photothermal efficacy and drug loading capability. Phenamil (Phe), an activator of bone morphogenetic protein pathways, was encapsulated into ZIF8 before loading onto gelatin nanofibrous (GF) scaffolds. The loaded Phe exhibited sustained and near-infrared triggered release profiles, which is capable of promoting bone morphogenetic protein 2 induced osteogenic differentiation even under near-infrared treatment. Moreover, our studies revealed that the photothermal effect of GF/ZIF8-Phe scaffolds can kill MG-63 cells in vitro and inhibit subcutaneous tumor growth in vivo. Therefore, the GF/ZIF8-Phe scaffold represents a novel bifunctional platform for tumor therapy and bone regeneration.

Genetically Engineered Nanohyaluronidase Vesicles: A Smart Sonotheranostic Platform for Enhancing Cargo Penetration of Solid Tumors

AbstractPrecise anti‐cancer therapy is hampered by aberrant tumor microenvironments (TME), which include the important features of the dense tumor extracellular matrix (ECM) and hypoxia. The capability of hyaluronidase (HAase) to degrade hyaluronic acid (HA), the main component of ECM, can prompt its rapid development in sonotherapeutics aimed at regulating the microenvironment. In this study, the authors design a bioengineering‐based smart enzymatic nanovesicle mHAase combined with purpurin 18 (P18) to form mHAase@nP18 that naturally anchors native HAase to the matrix metalloproteinase‐2 (MMP‐2) cleavable peptide. This nanovesicle system demonstrates a high expression of HAase and drug loading capability of the sonosensitizer, purpurin 18, for dual‐mode fluorescence/photoacoustic imaging‐guided sonodynamic therapy (SDT). Notably, mHAase@nP18 shows enhanced enzyme stability and activity in comparison to free HAase owing to avoidance of the protein crown shield; meanwhile, the released HAase causes a further elevation of its activity for SDT in an MMP‐2‐dependent manner. In vitro and in vivo results indicate the mHAase@nP18 can greatly enhance tumor penetration and alleviate hypoxia via HA degradation, further causing a heightened SDT effect. This work provides a promising strategy of stimuli‐responsive bioengineering of cell membrane vesicles for effective TME modulation and enhanced therapeutic results.

Borophene as an emerging 2D flatland for biomedical applications: current challenges and future prospects.

Recently, two-dimensional (2D)-borophene has emerged as a remarkable translational nanomaterial substituting its predecessors in the field of biomedical sensors, diagnostic tools, high-performance healthcare devices, super-capacitors, and energy storage devices. Borophene justifies its demand due to high-performance and controlled optical, electrical, mechanical, thermal, and magnetic properties as compared with other 2D-nanomaterials. However, continuous efforts are being made to translate theoretical and experimental knowledge into pragmatic platforms. To cover the associated knowledge gap, this review explores the computational and experimental chemistry needed to optimize borophene with desired properties. High electrical conductivity due to destabilization of the highest occupied molecular orbital (HOMO), nano-engineering at the monolayer level, chemistry-oriented biocompatibility, and photo-induced features project borophene for biosensing, bioimaging, cancer treatment, and theragnostic applications. Besides, the polymorphs of borophene have been useful to develop specific bonding for DNA sequencing and high-performance medical equipment. In this review, an overall critical and careful discussion of systematic advancements in borophene-based futuristic biomedical applications including artificial intelligence (AI), Internet-of-Things (IoT), and Internet-of-Medical Things (IoMT) assisted smart devices in healthcare to develop high-performance biomedical systems along with challenges and prospects is extensively addressed. Consequently, this review will serve as a key supportive platform as it explores borophene for next-generation biomedical applications. Finally, we have proposed the potential use of borophene in healthcare management strategies.