Peptide-Decorated Microneedles for the Detection of Microplastics.

The escalating utilization of plastics in daily life has resulted in pervasive environmental pollution and consequent health hazards. The challenge of detecting and capturing microplastics, which are imperceptible to the naked eye, is exacerbated by their diminutive size, hydrophobic surface properties, and capacity to absorb organic compounds. This study focuses on the application of peptides, constituted of specific amino acid sequences, and microneedles for the rapid and selective identification of microplastics. Peptides, due to their smaller size and greater environmental stability compared with antibodies, emerge as a potent solution to overcome the limitations inherent in existing detection methodologies. To immobilize peptides onto microneedles, this study employed microneedles embedded with gold nanorods, augmenting them with sulfhydryl (SH) groups at the peptides' termini. The sensor developed through this methodology exhibited efficient peptide binding to the microneedle tips, thereby facilitating the capture of microplastics. Raman spectroscopy was employed for the detection of microplastics, with the results demonstrating successful attachment to the microneedles. This novel approach not only facilitates localized analysis but also presents a viable strategy for the detection of microplastics across diverse environmental settings.

Nanotechnology-based delivery of therapeutics through the intranasal pathway and the blood-brain barrier for Alzheimer's disease treatment.

Background: drugs for Alzheimer's disease (AD) fail to exhibit efficacy in clinical trials for a number of reasons, a major one being blood-brain barrier (BBB) permeability. Meanwhile, the increasing incidence of this disease emphasizes the need for effective therapeutics. Herein, we discuss novel nanoplatform technologies developed for the effective delivery of AD drugs by traversing the BBB. Main text: the interfacial and surface chemistry of nanomaterials is utilized in several industries, including pharmaceutical, and has drawn considerable attention in the field of nanotechnology. Various reports have suggested the potential of nanotechnology for AD treatment, describing unique drug carriers that improve drug stability and solubility while maintaining therapeutic dosages. These nanotechnologies are harnessed for the transport of drugs across the BBB, with or without surface modifications. We also discuss the transfer of drugs via the nose-to-brain pathway, as intranasal delivery enables direct drug distribution in the brain. In addition, nanomaterial modifications that prolong drug delivery and improve safety following intranasal administration are addressed. Conclusion: although several studies have yielded promising results, limited efforts have been undertaken to translate research findings into clinical contexts. Nevertheless, nanomaterials hold considerable potential for the development of novel effective therapeutic solutions against AD.

Anticancer and Antibacterial Properties of Curcumin-Loaded Mannosylated Solid Lipid Nanoparticles for the Treatment of Lung Diseases.

Lung cancer and Mycobacterium avium complex infection are lung diseases associated with high incidence and mortality rates. Most conventional anticancer drugs and antibiotics have certain limitations, including high drug resistance rates and adverse effects. Herein, we aimed to synthesize mannose surface-modified solid lipid nanoparticles (SLNs) loaded with curcumin (Man-CUR SLN) for the effective treatment of lung disease. The synthesized Man-CUR SLNs were analyzed using various instrumental techniques for structural and physicochemical characterization. Loading curcumin into SLNs improved the encapsulation efficiency and drug release capacity, as demonstrated by high-performance liquid chromatography analysis. Furthermore, we characterized the anticancer effect of curcumin using the A549 lung cancer cell line. Cells treated with Man-CUR SLN exhibited an increased cellular uptake and cytotoxicity. Moreover, treatment with free CUR could more effectively reduce cancer migration than treatment with Man-CUR SLNs. Similarly, free curcumin elicited a stronger apoptosis-inducing effect than that of Man-CUR SLNs, as demonstrated by reverse transcription-quantitative PCR analysis. Finally, we examined the antibacterial effects of free curcumin and Man-CUR SLNs against Mycobacterium intracellulare (M.i.) and M.i.-infected macrophages, revealing that Man-CUR SLNs exerted the strongest antibacterial effect. Collectively, these findings indicate that mannose-receptor-targeted curcumin delivery using lipid nanoparticles could be effective in treating lung diseases. Accordingly, this drug delivery system can be used to target a variety of cancers and immune cells.

Dielectrophoretic Capture of Cancer-Derived Small-Extracellular-Vesicle-Bound Janus Nanoparticles via Lectin-Glycan Interaction.

Glycosylation is closely related to cellular metabolism and disease progression. In particular, glycan levels in cancer cells and tissues increase during cancer progression. This upregulation of glycosylation in cancer cells may provide a basis for the development of new biomarkers for the targeting and diagnosis of specific cancers. Here, they developed a detection technology for pancreatic cancer cell-derived small extracellular vesicles (PC-sEVs) based on lectin-glycan interactions. Lectins specific for sialic acids are conjugated to Janus nanoparticles to induce interactions with PC-sEVs in a dielectrophoretic (DEP) system. PC-sEVs are selectively bound to the lectin-conjugated Janus nanoparticles (lectin-JNPs) with an affinity comparable to that of conventionally used carbohydrate antigen 19-9 (CA19-9) antibodies. Furthermore, sEVs-bound Lectin-JNPs (sEVs-Lec-JNPs) are manipulated between two electrodes to which an AC signal is applied for DEP capture. In addition, the proposed DEP system can be used to trap the sEVs-Lec-JNP on the electrodes. Their results, which are confirmed by lectin-JNPs using the proposed DEP system followed by target gene analysis, provide a basis for the development of a new early diagnostic marker based on the glycan characteristics of PC-sEVs. In turn, these novel detection methods could overcome the shortcomings of commercially available pancreatic cancer detection techniques.

Tailoring tumor-recognizable hyaluronic acid-lipid conjugates to enhance anticancer efficacies of surface-engineered natural killer cells.

Natural killer (NK) cells have clinical advantages in adoptive cell therapy owing to their inherent anticancer efficacy and their ability to identify and eliminate malignant tumors. However, insufficient cancer-targeting ligands on NK cell surfaces often inhibit their immunotherapeutic performance, especially in immunosuppressive tumor microenvironment. To facilitate tumor recognition and subsequent anticancer function of NK cells, we developed hyaluronic acid (HA, ligands to target CD44 overexpressed onto cancer cells)-poly(ethylene glycol) (PEG, cytoplasmic penetration blocker)-Lipid (molecular anchor for NK cell membrane decoration through hydrophobic interaction) conjugates for biomaterial-mediated ex vivo NK cell surface engineering. Among these major compartments (i.e., Lipid, PEG and HA), optimization of lipid anchors (in terms of chemical structure and intrinsic amphiphilicity) is the most important design parameter to modulate hydrophobic interaction with dynamic NK cell membranes. Here, three different lipid types including 1,2-dimyristoyl-sn-glycero-3-phosphati-dylethanolamine (C14:0), 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE, C18:0), and cholesterol were evaluated to maximize membrane coating efficacy and associated anticancer performance of surface-engineered NK cells (HALipid-NK cells). Our results demonstrated that NK cells coated with HA-PEG-DSPE conjugates exhibited significantly enhanced anticancer efficacies toward MDA-MB-231 breast cancer cells without an off-target effect on human fibroblasts specifically via increased NK cell membrane coating efficacy and prolonged surface duration of HA onto NK cell surfaces, thereby improving HA-CD44 recognition. These results suggest that our HALipid-NK cells with tumor-recognizable HA-PEG-DSPE conjugates could be further utilized in various cancer immunotherapies.

Effect of driving characteristics and ambient temperature on the particle emissions during engine restart of spark ignition hybrid electric vehicle.

In this study, we analyzed particle emission characteristics in the engine restart (ER) phase of a hybrid electric vehicle (HEV) based on driving characteristics and ambient temperature. The ambient temperature was set at intervals of 10 °C from - 10 °C to 20 °C. ES-582.1, PPS-M, EEPS, and temperature sensors were installed to acquire hybrid control unit (HCU), particle number (PN), PN size distribution, and exhaust temperature data. The on board test route was conducted in the South Korean real driving emissions (RDE) certification route, consisting of urban, rural, and motorway phases. The test HEV was controlled by dividing the engine operation during driving into ER and normal phases. Within 5 s immediately after ER, it emitted PN equivalent to 90% of the total test emissions. The count of ER was higher in urban phases compared to rural and motorway phases. As the ambient temperature decreased, PN emissions increased regardless of the driving mode, but the ER PN percent decreased. Immediately after ER, PN emissions increased rapidly, peaked at around 2-3 s, and then decreased thereafter. The average engine-off time before ER was the longest in the urban phase, and the average ER exhaust temperature was the highest in the motorway phase. The size fraction of large particles increased as the ambient temperature decreased.

Targeted and efficient delivery of rifampicin to macrophages involved in non-tuberculous mycobacterial infection via mannosylated solid lipid nanoparticles.

Non-tuberculous mycobacterial infections are representative difficult-to-cure lung diseases with high incidence. Conventional treatments have several limitations such as negative side effects and increased drug resistance due to long-term administration. To overcome these limitations, there is a growing need for more stable drug delivery systems. Among the various drug delivery platforms developed thus far, solid lipid nanoparticles can be effectively loaded with hydrophobic substances and their physicochemical properties can be easily manipulated through surface modification, which makes them highly suitable drug delivery materials. Recent studies have reported the successful development of nanoparticles capable of selectively delivering drugs by targeting lectin-like receptors overexpressed on the surface of immune cells. Among these lectin-like receptors, the mannose receptor is a promising target because it is expressed on the surface of macrophages and is involved in immune activity. This study sought to synthesize rifampicin-loaded mannose surface-modified solid lipid nanoparticles (Man-RIF SLNs). The Man-RIF SLN synthesis process was first optimized, after which the characteristics of the synthesized particles were analyzed using dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). The surface modification with mannose was confirmed through FT-IR analysis. More importantly, the synthesized Man-RIF SLNs exhibited antibacterial and anti-biofilm properties against Mycobacterium intracellulare, a causative agent of non-tuberculous lung disease. Therefore, this study demonstrated that mannose receptor-targeted rifampicin delivery through solid lipid nanoparticles can be effectively applied to the treatment of non-tuberculous lung disease. Moreover, Man-RIF SLNs could also be used for the targeted delivery of drugs to several types of carcinoma cells or immune cells, as well as to treat lung diseases.

Antibacterial and biofilm-inhibiting cotton fabrics decorated with copper nanoparticles grown on graphene nanosheets.

Infectious pathogens can be transmitted through textiles. Therefore, additional efforts are needed to develop functional fabrics containing antimicrobial substances to prevent the growth of antibiotic-resistant bacteria and their biofilms. Here, we developed a cotton fabric coated with reduced graphene oxide (rGO) and copper nanoparticles (Cu NPs), which possessed hydrophobic, antimicrobial, and anti-biofilm properties. Once the graphene oxide was dip-coated on a cellulose cotton fabric, Cu NPs were synthesized using a chemical reduction method to fabricate an rGO/Cu fabric, which was analyzed through FE-SEM, EDS, and ICP-MS. The results of our colony-forming unit assays indicated that the rGO/Cu fabric possessed high antibacterial and anti-biofilm properties against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, Corynebacterium xerosis, and Micrococcus luteus. Particularly, the fabric could inhibit the growth of E. coli, C. xerosis, and M. luteus with a 99% efficiency. Furthermore, our findings confirmed that the same concentrations of rGO/Cu had no cytotoxic effects against CCD-986Sk and Human Dermal Fibroblast (HDF), human skin cells, and NIH/3T3, a mouse skin cell. The developed rGO/Cu fabric thus exhibited promising applicability as a cotton material that can maintain hygienic conditions by preventing the propagation of various bacteria and sufficiently suppressing biofilm formation while also being harmless to the human body.

Liquid-Metal Core-Shell Particles Coated with Folate and Phospholipids for Targeted Drug Delivery and Photothermal Treatment of Cancer Cells.

Recently, several methods have been used for cancer treatment. Among them, chemotherapy is generally used, but general anticancer drugs may affect normal cells and tissues, causing various side effects. To reduce the side effects and increase the efficacy of anticancer drugs, a folate-based liquid-metal drug nanodelivery system was used to target the folate receptor, which is highly expressed in cancer cells. A phospholipid-based surface coating was formed on the surface of liquid-metal nanoparticles to increase their stability, and doxorubicin was loaded as a drug delivery system. Folate on the lipid shell surface increased the efficiency of targeting cancer cells. The photothermal properties of liquid metal were confirmed by near-infrared (NIR) laser irradiation. After treating cancerous and normal cells with liquid-metal particles and NIR irradiation, the particles were specifically bound to cancer cells for drug uptake, confirming photothermal therapy as a drug delivery system that is expected to induce cancer cell death through comprehensive effects such as vascular embolization in addition to targeting cancer cells.

Glycan targeting nanoparticle for photodynamic immunotherapy of melanoma.

Interaction between tumour cells and macrophages enables cancer cells to evade immune detection and clearance by interfering with macrophage phagocytosis. The anti-phagocytic signals regulated by anti-phagocytic proteins are termed "don't eat me" signals; these signals include sialic acid-binding immunoglobulin-type lectin-10 (Siglec-10) and the recently revealed CD24 immune checkpoint (ICP). In this study, we demonstrate that targeting a specific glycan on CD24 exhibits the potential to inhibit ICP. Sambucus nigra agglutinin (SNA), a sialic acid-binding lectin, was employed to block CD24 and to enhance phagocytosis in melanoma tumours. In addition, we prepared SNA-conjugated hollow gold-iron oxide nanoparticles for photothermal therapy of tumours. Our findings show that the combination treatment of SNA-conjugated photothermal nanoparticles and near-infrared exposure successfully augments tumour cell phagocytosis both in vitro and in vivo models.

Nanosome-Mediated Delivery Of Hdac Inhibitors and Oxygen Molecules for the Transcriptional Reactivation of Latent Hiv-Infected Cd4+ T Cells.

The treatment of human immunodeficiency virus (HIV) infection is notoriously difficult due to the ability of this virus to remain latent in the host's CD4+ T cells. Histone deacetylases (HDACs) interfere with DNA transcription in HIV-infected hosts, resulting in viral latency. Therefore, HDAC inhibitors can be used to activate viral transcription in latently infected cells, after which the virus can be eliminated through a shock-and-kill strategy. Here, a drug delivery system is developed to effectively deliver HDAC inhibitors to latent HIV-infected cells. Given that the efficacy of HDAC inhibitors is reduced under hypoxic conditions, oxygen-containing nanosomes are used as drug carriers. Oxygen-containing nanosomes can improve the efficiency of chemotherapy by delivering essential oxygen to cells. Additionally, their phospholipid bilayer structure makes them uniquely well-suited for drug delivery. In this study, a novel drug delivery system is developed by taking advantage of the oxygen carriers in these oxygen nanosomes, incorporating a multi-drug strategy consisting of HDAC inhibitors and PKA activators, and introducing CXCR4 binding peptides to specifically target CD4+ T cells. Oxygen nanosomes with enhanced targeting capability through the introduction of the CXCR4 binding peptide mitigate drug toxicity and slow down drug release. The observed changes in the expression of p24, a capsid protein of HIV, indirectly confirm that the proposed drug delivery system can effectively induce transcriptional reactivation of HIV in latent HIV-infected cells.

Lipid-based colloidal nanoparticles for applications in targeted vaccine delivery.

Bioactive molecules and their effects have been influenced by their solubility and administration route. In many therapeutic reagents, the performance of therapeutics is dependent on physiological barriers in the human body and delivery efficacy. Therefore, an effective and stable therapeutic delivery promotes pharmaceutical advancement and suitable biological usage of drugs. In the biological and pharmacological industries, lipid nanoparticles (LNPs) have emerged as a potential carrier to deliver therapeutics. Since studies reported doxorubicin-loaded liposomes (Doxil®), LNPs have been applied to numerous clinical trials. Lipid-based nanoparticles, including liposomes, solid lipid nanoparticles (SLNs), and nanostructured lipid nanoparticles, have also been developed to deliver active ingredients in vaccines. In this review, we present the type of LNPs used to develop vaccines with attractive advantages. We then discuss messenger RNA (mRNA) delivery for the clinical application of mRNA therapeutic-loaded LNPs and recent research trend of LNP-based vaccine development.

Physiological significance of elevated levels of lactate by exercise training in the brain and body.

For the past 200 years, lactate has been regarded as a metabolic waste end product that causes fatigue during exercise. However, lactate production is closely correlated with energy metabolism. The lactate dehydrogenase-catalyzed reaction uses protons to produce lactate, which delays ongoing metabolic acidosis. Of note, lactate production differs depending on exercise intensity and is not limited to muscles. Importantly, controlling physiological effect of lactate may be a solution to alleviating some chronic diseases. Released through exercise, lactate is an important biomarker for fat oxidation in skeletal muscles. During recovery after sustained strenuous exercise, most of the lactate accumulated during exercise is removed by direct oxidation. However, as the muscle respiration rate decreases, lactate becomes a desirable substrate for hepatic glucose synthesis. Furthermore, improvement in brain function by lactate, particularly, through the expression of vascular endothelial growth factor and brain-derived neurotrophic factor, is being increasingly studied. In addition, it is possible to improve stress-related symptoms, such as depression, by regulating the function of hippocampal mitochondria, and with an increasingly aging society, lactate is being investigated as a preventive agent for brain diseases such as Alzheimer's disease. Therefore, the perception that lactate is equivalent to fatigue should no longer exist. This review focuses on the new perception of lactate and how lactate acts extensively in the skeletal muscles, heart, brain, kidney, and liver. Additionally, lactate is now used to confirm exercise performance and should be further studied to assess its impact on exercise training.

Gelatin-Gallic Acid Microcomplexes Release GO/Cu Nanomaterials to Eradicate Antibiotic-Resistant Microbes and Their Biofilm.

Wound-infecting bacteria are typically Pseudomonas aeruginosa and Staphylococcus epidermidis, both of which form biofilms and become resistant to antibiotics. To solve this problem, copper nanoparticles (Cu) on graphene oxide (GO) nanosheets were used as antibacterial materials. Since the excessive use of antibacterial substances is fatal to normal tissues, GO/Cu was encapsulated with a gelatin complex to lower the cytotoxicity. Among the catechol-based substances, gallic acid (GA), which has anti-inflammatory and antibacterial properties, was used in this study to impart stability to the gelatin complex. Gelatin (GE) and gallic acid (GA) were combined by a crosslinking method using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)/N-hydroxysuccinimide (NHS) as a crosslinker, and the crosslinking was confirmed by Fourier transform infrared (FT-IR), 1H NMR, and the fluorescence property of GA. The GO/Cu@GE-GA microcomplexes exhibited more antibacterial effect against Gram-positive bacteria (S. epidermidis) and Gram-negative bacteria (P. aeruginosa) than when GO/Cu alone was used, and the antibiofilm effect was also confirmed. The cytotoxicity evaluation for human skin cells (human dermal fibroblast (HDF)) at the same concentration showed that it had low cytotoxicity and biocompatibility. This study shows the potential of antimicrobial gelatin microcomplex in prohibiting infectious bacteria and their biofilms and controlling the release of antimicrobial substances.

Sensitive and specific capture of polystyrene and polypropylene microplastics using engineered peptide biosensors.

Owing to increased environmental pollution, active research regarding microplastics circulating in the ocean has attracted significant interest in recent times. Microplastics accumulate in the bodies of living organisms and adversely affect them. In this study, a new method for the rapid detection of microplastics using peptides was proposed. Among the various types of plastics distributed in the ocean, polystyrene and polypropylene were selected. The binding affinity of the hydrophobic peptides suitable for each type of plastic was evaluated. The binding affinities of peptides were confirmed in unoxidized plastics and plasma-oxidized plastics in deionised or 3.5% saline water. Also, the detection of microplastics in small animals' intestine extracts were possible with the reported peptide biosensors. We expect plastic-binding peptides to be used in sensors to increase the detection efficiency of microplastics and potentially help separate microplastics from seawater.

Surface glycan targeting for cancer nano-immunotherapy.

Cancer immunotherapy is an emerging therapeutic strategy for cancer treatment. Most of the immunotherapeutics approved by the FDA regulate the innate immune system and associated immune cell activity, with immune check inhibitors in particular having transformed the field of cancer immunotherapy due to their significant clinical potential. However, previously reported immunotherapeutics have exhibited undesirable side effects, including autoimmune toxicity and inflammation. Controlling these deleterious responses and designing therapeutics that can precisely target specific regions are thus crucial to improving the efficacy of cancer immunotherapies. Recent studies have reported that cancer cells employ glycan-immune checkpoint interactions to modulate immune cell activity. Thus, the recognition of cancer glycan moieties such as sialoglycans may improve the anticancer activity of immune cells. In this review, we discuss recent advances in cancer immunotherapies involving glycans and glycan-targeting technologies based on nanomaterial-assisted local delivery systems.

Photocatalytic activity of nanoparticles: the development of the standardized measurement for physiological conditions.

Recently a new International Standard for testing nanomaterial photocatalytic activity under physiological conditions was issued by Technical Committee 229 (Nanotechnologies) of the International Organization for Standardization (ISO 20814:2019 Nanotechnologies-Testing the photocatalytic activity of nanoparticles for NADH oxidation). The document offers a robust, high throughput photocatalytic assay using a bio-compatible indicator nicotinamide amide dinucleotide (NAD) and provides a screening tool to gauge nanomaterial potency for phototoxicity. This paper describes the measurement principles behind this assay, the scope of the standard and its validation through an interlaboratory comparison study using a traceable standard reference material (SRM 1898).

Oxygen transport to mammalian cell and bacteria using nano-sized liposomes encapsulating oxygen molecules.

Hypoxic microenvironments emerge as tumor grow, leading to the over-expression and stabilization of hypoxia-inducible factor 1-alpha (HIF-1α). HIF-1α lowers the sensitization against chemotherapy, radiation therapy and photodynamic therapy in cancer. In this study, nano-sized oxygen carrier, namely oxygen dissolved nanoliposome (ODL) was synthesized, and oxygen was efficiently delivered to different types of mammalian cells to help relieve hypoxia. ODL confirmed that oxygen was released without inducing toxicity to cells. After artificially creating hypoxia in cancer cells, normal cells, and immune cells; various parameters such as cell morphology, HIF-1α expression, and degree of hypoxia were examined. The cellular environment was found to be altered by treatment with the ODL. Under hypoxia, the shape of the cells changed, and the cells began to die. After treatment with the ODL, the degree of hypoxia was reduced, indicating that HIF-1α expression and the rate of cell death decreased. Furthermore, bacteria proliferation was observed with the ODL. Therefore, ODL can be used for oxygen delivery platform in cancer therapy. ODL has a potential application in other microorganisms which needs future research.

Inhalable nanoparticles delivery targeting alveolar macrophages for the treatment of pulmonary tuberculosis.

Pulmonary tuberculosis is a highly prevalent respiratory disease that affects approximately a quarter of the world's population. The drug treatment protocol for tuberculosis is complex because the Mycobacterium tuberculosis (M. tuberculosis) invades macrophages and begins to infect. Thus treatment usually includes combination therapy with several drugs such as rifampicin, pyrazinamide, isoniazid, and ethambutol over a long dosing period. Therefore, drug-delivery technologies have been developed to improve patient compliance with medication, reduce adverse effects, and increase effectiveness of the treatment. In the present review, we have discussed recent inhalable nanopharmaceutical systems for the treatment of pulmonary tuberculosis and investigated their design and effectiveness. We examined the underlying processes and characteristics of spray-drying technology and studied the formulation of a dry carrier using spray-drying method. Moreover, we reviewed various research articles on pulmonary delivery of nanoparticles using these carriers, and studied their alveolar macrophage targeting ability and therapeutic effects. Further, we appraised the effectiveness of nanoparticle inhalation therapy for the treatment of pulmonary tuberculosis and its potential as a treatment strategy for lung diseases.

Sustained Release of Bone Morphogenetic Protein-2 through Alginate Microbeads Enhances Bone Regeneration in Rabbit Tibial Metaphyseal Defect Model.

Bone morphogenetic protein-2 (BMP-2) is widely used to enhance bone regeneration. However, because of its short half-life and rapid disappearance, large amounts of BMP-2 are needed, leading to unintended side effects. In this study, BMP-2-encapsulated alginate microbeads (AM) were used to enhance bone regeneration. Enzyme-linked immunosorbent assay confirmed the sustained release of BMP-2 from AM. Vascular endothelial growth factor (VEGF)-adsorbing aptamer-conjugated hydroxyapatite (Apt-HA) was used for osteoconduction and dual delivery of VEGF and BMP-2. For in vivo bone regeneration evaluation, the grafts (1) Apt-HA + phosphate-buffered saline (PBS), (2) Apt-HA + AM without BMP-2, (3) Apt-HA + BMP-2, and (4) Apt-HA + AM encapsulated with BMP-2 were implanted into rabbit tibial metaphyseal defects. After four weeks, micro-computed tomography (CT), histological, and histomorphometric analyses were performed to evaluate bone regeneration. The Apt-HA + AM with BMP-2 group revealed a significantly higher new bone volume and bone volume/total volume (BV/TV) in both cortical and trabecular bone than the others. Furthermore, as evaluated by histomorphometric analysis, BMP-2 AM exhibited a significantly higher bone formation area than the others, indicating that AM could be used to efficiently deliver BMP-2 through sustained release. Moreover, the combined application of BMP-2-encapsulated Apt-HA + AM may effectively promote bone regeneration.