Drug Delivery Strategies Research Articles

Efficient encapsulation of a model drug in chitosan cathodic electrodeposition: Preliminary analysis using FTIR, UV–vis, and NMR spectroscopy

This study investigates the preliminary efficacy of drug encapsulation in chitosan hydrogels by cathodic electrodeposition for the encapsulation of the aromatic dye methyl orange to enhance drug delivery in biological systems. Chitosan, a biocompatible and transparent polymer, is known for its ability to effectively encapsulate and transport therapeutic agents, which is critical for sustained and targeted drug release. Methyl orange was selected as a model drug to study the effects of deposition and immersion times on encapsulation efficiency. The effects of deposition and immersion times on encapsulation efficiency were analyzed by synthesizing multilayer hydrogels via electrochemical oxidation. Characterization techniques, including UV–visible spectroscopy, FTIR, and NMR, were employed; FTIR indicated an effective absorption of 4.34 % for Td50Ti60, while UV–Vis showed 46.41 % at Td60Ti50. NMR analysis revealed effective concentrations of 0.47 mM for Td70Ti60 and 0.38 mM for Td60Ti50, indicating that longer immersion times enhance absorption. These findings provide a foundation for further studies aimed at optimizing drug delivery strategies and improving the therapeutic efficacy of encapsulated agents in biological applications.

Clarithromycin-tailored cubosome: A sustained release oral nano platform for evaluating antibacterial, anti-biofilm, anti-inflammatory, anti-liver cancer, biocompatibility, ex-vivo and in-vivo studies

The clinical implication of clarithromycin (CLT) is compromised owing to its poor solubility and, subsequently, bioavailability, unpalatable taste, rapid metabolism, short half-life, frequent dosing, and adverse effects. The present investigation provides an innovative sustained-release oral drug delivery strategy that tackles these challenges. Accordingly, CLT was loaded into a cubosome, a vesicular system with a bicontinuous cubic structure that promotes solubility and bioavailability, provides a sustained release system combating short half-life and adverse effects, masks unpleasant taste, and protects the drug from destruction in gastrointestinal tract (GIT). Nine various formulas were fabricated using the emulsification method. The resulting vesicles increased the encapsulation efficiency (EE %) from 57.64 ± 0.04 % to 96.80 ± 1.50 %, the particle size (PS) from 147.30 ± 21.77 nm to 216.61 ± 5.37 nm, and the polydispersity index (PDI) values ranged from 0.117 ± 0.024 to 0.278 ± 0.073. The zeta potential (ZP) changed from −20.65 ± 2.01 mV to −33.98 ± 2.60 mV. Further, the release profile exhibited a dual release pattern within 24 h., with the percentage of cumulative release (CR %) expanding from 30.06 ± 0.42 % to 98.49 ± 2.88 %, optimized formula was found to be CC9 with EE % = 96.80 ± 1.50 %, PS = 216.61 ± 5.37 nm, ZP = −33.98 ± 2.60 mV, PDI = 0.117 ± 0.024, CR % = 98.49 ± 2.88 % and IC50 of 0.74 ± 0.19 µg/mL against HepG-2 cells with scattered unilamellar cubic non-agglomerated vesicles. Additionally, it exhibited higher anti-MRSA biofilm, relative bioavailability (2.8 fold), and anti-inflammatory and antimicrobial capacity against Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis, and Staphylococcus aureus compared to free CLT. Our data demonstrate that cubosome is a powerful nanocarrier for oral delivery of CLT, boosting its biological impacts and pharmacokinetic profile.

Developing a delivery strategy for combined drug treatment with multi-targeting immunoliposomes

With the use of targeting delivery systems, drugs can be specifically administered to tumor cells based on the abundant expression of cell surface markers with minimal expression in normal cells. However, development of treatments using this highly specific approach requires empirical optimization of the tumor cell type, cell surface markers and cytotoxic cargo. In this study, we developed a combined targeting drug delivery strategy for lung cancer that utilizes two liposome-encapsulated topoisomerase inhibitors, liposomal doxorubicin (LD) and liposomal irinotecan (LI). First, we evaluated different combination conditions for the drugs and found that co-administration or administration of LD followed by LI produced similar tumor inhibition trends. In contrast, treatment of with LI followed by LD was less effective at inhibiting tumor growth. Next, we targeted the liposomes against two ligands that are overexpressed in lung cancers: PD-L1 and GRP-78. To do so, we fabricated immunoliposomes conjugated with PD-L1 Fab or GRP-78 antibody. In animal models, combinations of GRP-78-targeted LI and PD-L1-targeted LD showed 92% tumor inhibition which is higher than other combination treatments or each drug alone. Our findings, therefore, indicate that combining different targeting moieties with LI and LD may enhance drug delivery and reduce tumor burden.

Application of Nanocomposites and Nanoparticles in Treating Neurodegenerative Disorders.

Neurodegenerative diseases represent a formidable global health challenge, affecting millions and imposing substantial burdens on healthcare systems worldwide. Conditions, like Alzheimer's, Parkinson's, and Huntington's diseases, among others, share common characteristics, such as neuronal loss, misfolded protein aggregation, and nervous system dysfunction. One of the major obstacles in treating these diseases is the presence of the blood-brain barrier, limiting the delivery of therapeutic agents to the central nervous system. Nanotechnology offers promising solutions to overcome these challenges. In Alzheimer's disease, NPs loaded with various compounds have shown remarkable promise in preventing amyloid-beta (Aβ) aggregation and reducing neurotoxicity. Parkinson's disease benefits from improved dopamine delivery and neuroprotection. Huntington's disease poses its own set of challenges, but nanotechnology continues to offer innovative solutions. The promising developments in nanoparticle-based interventions for neurodegenerative diseases, like amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS), have offered new avenues for effective treatment. Nanotechnology represents a promising frontier in biomedical research, offering tailored solutions to the complex challenges posed by neurodegenerative diseases. While much progress has been made, ongoing research is essential to optimize nanomaterial designs, improve targeting, and ensure biocompatibility and safety. Nanomaterials possess unique properties that make them excellent candidates for targeted drug delivery and neuroprotection. They can effectively bypass the blood-brain barrier, opening doors to precise drug delivery strategies. This review explores the extensive research on nanoparticles (NPs) and nanocomposites in diagnosing and treating neurodegenerative disorders. These nanomaterials exhibit exceptional abilities to target neurodegenerative processes and halt disease progression.

Chalcogenides encapsulated Pt-doped carbon quantum dot (Pt@CQD) as a carrier for the controlled release of lapachone: Outlook from theoretical calculations

While cancer remains a significant health concern for humans, and is a serious and life-threatening disease, this research introduces an innovative drug delivery strategy employing platinum-doped carbon quantum dots (Pt@CQD) decorated with chalcogenide (O, S, Te) atoms for targeted delivery of the anti-inflammatory drug lapachone (LPC), which was analysed through density functional theory (DFT) at the ωB97XD/def2svp level of theory. Adsorption studies indicated exothermic behaviour, with negative energies for LPC_Pt@CQD, LPC_OdecPt@CQD, LPC_SdecPt@CQD, and LPC_TedecPt@CQD with corresponding values of −25.549 kcal/mol, −24.583 kcal/mol, −24.629 kcal/mol and − 24.419 kcal/mol respectively, indicating their chemisorption strengths. The quantum theory of atoms in molecules (QTAIM) and non-covalent interaction (NCI) analyses highlight weak and partial interactions among the complexes. Significantly, the engineered systems exhibit notable drug-release properties, especially LPC_OdecPt@CQD, where we observed a considerably slight physisorption and an adsorption energy of 10.277 kcal/mol and a protonation energy gap (ΔE) of 2.648 eV which balances effective adsorption and the ability to release the drug when needed. Furthermore, molecular dynamics and reactivity analysis revealed high stability and biological activity respectively among the designed systems, making them promising candidates for therapeutic delivery and holding potential for further in vivo and clinical investigations.

Investigating a novel therapeutic composition for dry eye syndrome management: In vitro and in vivo studies

Dry eye syndrome (DES) presents a significant challenge in ophthalmic care, necessitating innovative approaches for effective management. This research article introduces a multifaceted strategy to address DES through the development of ocular inserts utilizing advanced technologies such as hot-melt extrusion (HME) and the CaliCut post-extrusion system. The formulation includes key ingredients targeting different layers of the tear film and associated inflammation, including hydroxypropyl cellulose (HPC), polyethylene glycol (PEG), castor oil, and dexamethasone. The study incorporates a Design of Experiments (DoE) approach, integrating HME and the precise stretching and cutting technique of CaliCut for manufacturing consistency and dimensional control of the inserts. The developed insert(s) have been systematically characterized for their physicochemical properties, release profile, and in vivo efficacy. In silico molecular docking studies have also been conducted to assess the binding affinities of formulation components with ocular mucin, elucidating their binding affinities. Preliminary results demonstrate promising potential for the developed insert in managing DES, offering preservative-free treatment, sustained drug delivery, and improved patient compliance. This study highlights the integration of advanced technologies and formulation strategies in ocular drug delivery for effective DES management.

An Overview of the Anticancer Potential of Silver Nanostructures against Cervical Cancer.

Women are impacted by the extremely common cancer known as cervical cancer worldwide. Although preventive vaccines for cervical cancer are successful, treatment of cervical cancer is far less satisfactory because of multidrug resistance and side effects. There is an increasing need for alternative treatment modalities due to the rather aggressive and non-specific nature of conventional chemotherapeutics. With the advent of new technologies, scientists are working harder to create novel drug delivery strategies for chemotherapy of cervical cancer. Metal nanoparticles, and particularly silver nanoparticles, are a relatively new class with a lot of promise in the field of cancer biology. Nanoparticle therapeutics are attractive platforms for clinically relevant drug development because of their powerful anti-cancer properties, correspondingly attenuated side effects, and cancer-specific targeting. In this review, we provide an overview of the most recent uses of nanotechnology, particularly silver nanostructures, in the diagnosis and treatment of cervical cancer. The salient features of silver nanoparticle-based therapeutic concepts that are novel, viable, and attainable are emphasized in this review, along with those that pose a significant obstacle to their progress toward clinical application.

Recent Advancements in Drug Delivery System in Lung Cancer

Eliminating the fact that the use of free pharmaceuticals in conventional dosage forms usually involves difficulties in hitting the target site at the appropriate dose after or during a correct time period, medication targeting specific organs and tissues became one of the century's most important initiatives. Thus, finding new drug delivery strategies and modes of action are lines of battle. Difficulties are still encountered with radiation therapy to accurately track the movements of lung tumors while treatments are being admitted. The development of MRI-linac hybrid system prototypes offers the possibility of real-time, ionization-free tumor imaging. This study assesses how well lung tumor tracking algorithms function on five healthy participants' cine-MRI sagittal images. The targets were vascular structures that could be seen. Lung cancer is the leading cause of mortality in the world. This is one of the heterogeneous diseases that include, at the basic level, two main subtypes: small cell lung cancer and non-small cell lung cancer. Less than 20% of patients with LC survive for 5 years on average despite recent improvements in treatment. The effectiveness of existing therapeutic techniques is impaired because of severe off-target effects and innate or acquired medication resistance. The two major types of lung cancers are SCLC and NSCLC; among these, the former is the most frequently diagnosed. Lung cancers account for the highest mortality rate due to cancer. The application of nanomedicines can partially overcome the failures that are associated with the anticancer therapies against NSCLC. One of the nanoparticle subfields that hold out much promise for better delivery while ensuring stability and sufficient bioavailability of administered anticancer medications is nanomedicine.

Novel targeting liposomes with enhanced endosomal escape for co-delivery of doxorubicin and curcumin

Effective endosomal escape is crucial for enhancing the efficiency of nanodrug delivery systems. In this study, we developed a novel liposomal system utilizing acid-sensitive N-(3-amino-propyl) imidazole cholesterol (IM-Chol), specifically designed for the targeted co-delivery of doxorubicin (DOX) and curcumin (CUR) to hepatocellular carcinoma (HCC). Designated as GA-IM-LIP@DOX/CUR, this liposomal system incorporates glycyrrhetinic acid (GA) to improve target specificity toward HCC cells. Notably, both drugs exhibited pH-sensitive release profiles, facilitating precise drug release within acidic environments. Our investigation into cellular uptake demonstrated that modified liposomes, GA-IM-LIP@FITC and IM-LIP@FITC, achieved progressively enhanced intracellular accumulation of FITC compared to unmodified liposomes. Competitive inhibition assays utilizing free GA further validated the targeting efficacy of GA. Moreover, the GA-IM-LIP@FITC and IM-LIP@FITC groups exhibited rapid endosomal escape of FITC within the first two hours, in contrast to delayed escape observed in the LIP@FITC group, confirming that the protonation of IM-Chol promotes drug release into the cytosol. In vivo studies substantiated that GA-IM-LIP@DOX/CUR effectively inhibited tumor growth. This research provides significant insights into the design and functionality of the GA-IM-LIP@DOX/CUR liposomal system, underscoring its potential to enhance drug delivery strategies in the treatment of HCC.

Igniting tumour microenvironment in triple-negative breast cancer using a mannose/hyaluronic acid dual-coated Ganoderma polysaccharide-superparamagnetic iron oxide nanocomplex for combinational therapies

Eliciting tumour microenvironment (TME) activation in triple-negative breast cancer (TNBC) is crucial for effective anti-tumour therapies. The aim of this study is to employ pharmaceutical approaches to precisely deliver Ganoderma polysaccharide (GPS) to tumour sites, thereby enhancing TME activation. We first established a direct link between the accumulation of GPS within tumours and its efficacy in the TME activation. Building upon this insight, we then engineered a mannose/hyaluronic acid dual-coated GPS-loaded superparamagnetic iron oxide nanocomplex (Man/HA/GPS-SPIONs) with a particle size of 33.8 ± 1.6 nm and a zeta potential of −22.4 ± 3.5 mV, capable of precise tumour accumulation through magnet-assisted targeting and internalisation by tumour-associated macrophages (TAMs) and tumour cells, facilitated by dual ligand modification. In vitro, Man/HA/GPS-SPIONs effectively induced M1 polarisation of macrophages (CD86+ cells: 38.6 ± 2.8%), curbed 4T1 cell proliferation (viability: 47.3 ± 2.9%) and heightened Th1 cytokine release. Significantly, in vivo, Man/HA/GPS-SPIONs notably suppressed tumour growth (tumour index: 0.048 ± 0.005), fostered M1 polarisation of TAMs (CD45+F4/80+CD86+ cells: 26.1 ± 7.2%), consequently bolstering intratumoural T cytotoxic cells. This enhancement was intricately tied to the efficient co-delivery of GPS and iron ions to the tumours, made possible by the Man/HA/GPS-SPIONs delivery system. The synergistic effects with paclitaxel (PTX, inhibition rate: 61.2 ± 4.3%) and PD-1 inhibitors (inhibition rate: 69.8 ± 7.6%) underscored the translational potential of this approach. By harnessing a well-conceived iron-based drug delivery strategy, this study amplifies the tumour immune modulatory potential of natural polysaccharides, offering insightful guidance for interventions in the TME and synergistic therapies.

Mesalamine-Loaded Microsponges As A Potential Strategy For Colon-Specific Drug Delivery

Mesalamine-Loaded Microsponges As A Potential Strategy For Colon-Specific Drug Delivery

Ferulic Acid-Loaded Nanostructure Maintains Brain Levels of ACh, Glutamate, and GABA and Ameliorates Anxiety and Memory Impairments Induced by the D-Galactose Aging Process in Rats.

Population aging is a global reality driven by increased life expectancy. This demographic phenomenon is intrinsically linked to the epidemic of cognitive disorders such as dementia and Alzheimer's disease, posing challenges for elderly and their families. In this context, the search for new therapeutic strategies to prevent or minimize cognitive impairments becomes urgent, as these deficits are primarily associated with oxidative damage and increased neuroinflammation. Ferulic acid (FA), a natural and potent antioxidant compound, is proposed to be nanoencapsulated to target the central nervous system effectively with lower doses and an extended duration of action. Here, we evaluated the effects of the nanoencapsulated FA on d-galactose (d-Gal)- induced memory impairments. Male Wistar adult rats were treated with ferulic acid-loaded nanocapsules (FA-Nc) or non-encapsulated ferulic acid (D-FA) for 8weeks concurrently with d-Gal (150mg/kg s.c.) injection. As expected, our findings showed that d-Gal injection impaired memory processes and increased anxiety behavior, whereas FA-Nc treatment ameliorated these behavioral impairments associated with the aging process induced by d-Gal. At the molecular level, nanoencapsulated ferulic acid (FA-Nc) ameliorated the decrease in ACh and glutamate induced by d-galactose (d-Gal), and also increased GABA levels in the dorsal hippocampus, indicating its therapeutic superiority. Additional studies are needed to elucidate the mechanisms underlying our current promising outcomes. Nanoscience applied to pharmacology can reduce drug dosage, thereby minimizing adverse effects while enhancing therapeutic response, particularly in neurodegenerative diseases associated with aging. Therefore, the strategy of brain-targeted drug delivery through nanoencapsulation can be effective in mitigating aging-related factors that may lead to cognitive deficits.

Hyaluronic Acid in Nanopharmaceuticals: An Overview.

Hyaluronic acid (HA) is a naturally occurring, long, unbranched polysaccharide that plays a critical role in maintaining skin structure and hydration. Its unique properties make it a valuable component in the field of nanopharmaceuticals. The combination of HA into nanopharmaceuticals enhances its ability to interact with various therapeutic agents, improving the delivery and efficacy of drugs. HA-based nanoparticles, including solid lipid nanoparticles, and polymeric nanogels, offer controlled release, enhanced stability, and targeted delivery of therapeutic agents. These innovations significantly improve therapeutic outcomes and reduce side effects, making HA an essential tool in modern medicine. In general, HA-modified liposomes enhance drug encapsulation and targeting, while HA-modified solid lipid nanoparticles (SLNs) provide a solid lipid core for drug encapsulation, offering controlled release and stability. This article provides an overview of the potential applications and recent advancements of HA in nanopharmaceuticals, emphasizing its significant impact on the evolving field of targeted drug delivery and advanced therapeutic strategies. By delving into the unique properties of HA and its compatibility with various therapeutic agents, this review underscores the promising potential of HA in revolutionizing nanopharmaceuticals.

Molecular farming expression of recombinant fusion proteins applied to skincare strategies.

This review discusses the current research progress in molecular farming technology in the field of skincare, with an emphasis on molecular farming expression strategies. The strategies of transdermal drug delivery and their advantages are also highlighted. The expression of cosmetically relevant fused proteins has become an important way to enhance the efficacy of the proteins. Therefore, we also discuss the feasibility and strategies for expressing fusion proteins in A. thaliana, specifically the fusion of Epidermal growth factor (EGF) to a cell-penetrating peptide (CPP), in which the production can be greatly enhanced via plant expression systems since these systems offer higher biosecurity, flexibility, and expansibility than prokaryotic, animal and mammalian expression systems. While the fusion of EGF to CCP can enhance its transdermal ability, the effects of the fusion protein on skin repair, melasma, whitening, and anti-aging are poorly explored. Beyond this, fusing proteins with transdermal peptides presents multiple possibilities for the development of tissue repair and regeneration therapeutics, as well as cosmetics and beauty products. As certain plant extracts are known to contain proteins beneficial for skin health, the expression of these proteins in plant systems will better maintain their integrity and biological activities, thereby facilitating the development of more effective skincare products.

NANOMEDICINE BREAKTHROUGH: REVOLUTIONIZING CERVICAL CANCER TREATMENT WITH PRECISION DRUG DELIVERY

Cervical cancer, a global health issue, is a major concern, particularly in regions with limited healthcare resources. To address this, targeted drug delivery strategies have emerged as promising solutions. These involve delivering therapeutic agents directly to cancerous cells, minimizing systemic side effects, and enhancing treatment efficacy. Delivery systems like nanoparticles, liposomes, polymeric micelles, hydrogels, and local drug delivery devices have been developed to overcome barriers like drug resistance and limited penetration. Emerging targeting strategies like tumor-specific ligands, immunotherapy, virotherapy, and gene therapy are also promising for improving treatment specificity and efficacy in cervical cancer. These approaches address the intricate cellular pathways involved in the disease progression, paving the way for more personalized and effective treatments. The synergy between advancements in drug delivery technologies and targeting strategies offers hope for a future where cervical cancer can be effectively managed and potentially eradicated. KEYWORDS: Targeted drug delivery, Nanoparticles, Immunotherapy, Gene therapy, Personalized treatments, Cervical cancer

Facile fabrication of cedrol nanoemulsions with deep transdermal delivery ability and high safety for effective androgenic alopecia treatment

The successful treatment of androgenic alopecia (AGA) hinges on an effective transdermal drug delivery strategy, a challenge that requires urgent attention. In this study, we introduce a novel approach utilizing cedrol nanoemulsions (CD-NEs) for AGA treatment. Our findings demonstrate that cedrol (CD) effectively inhibits the expression of 5α-reductase 2 (5αR2), akin to the FDA-approved drug finasteride, while also surpassing it in terms of promoting cell proliferation. Through formulation optimization, we have developed stable CD-NEs suitable for large-scale production. Experimental and molecular dynamics simulations further reveal that CD-NEs enhance transdermal penetration by altering lipid organization, facilitating CD delivery to deeper skin layers via a trans-epidermal pathway. In vivo studies conducted on AGA model C57BL/6 mice demonstrate that CD-NEs significantly promote hair follicle regeneration, accelerating the transition of hair follicles from the telogen phase to the anagen phase. Moreover, CD-NEs treatment leads to a significant reduction in dihydrotestosterone (DHT) levels in the skin while maintaining stasis levels in serum, underscoring its efficacy in targeting androgenetic pathways with high safety. This comprehensive analysis sheds light on the efficacy and mechanism of action of CD-NEs in hair regeneration, offering valuable insights for future clinical applications in AGA treatment.

Current Formulation Strategies to Design Novel Carriers for Targeted Drug Delivery and Management of Infectious Keratitis: A Comprehensive Review on the Present State of the Art

Objective: Infectious keratitis is a pernicious disease that affects the anterior segment of the eye and is one the leading causes of blindness worldwide. This disease may cause severe visual impairment or permanent vision damage if left untreated. Discussion: No doubt there are many conventional drug delivery systems to treat ocular keratitis, yet it is the fifth leading cause of blindness globally. This is the result of the eye's complex anatomy and barrier system, which restricts the total ocular contact time of the conventional formulations resulting in underdosing. The widely used traditional formulations to treat keratitis, like antibiotic eye drops and ointments, are rendered useless due to less ocular contact time and low therapeutic drug levels at the target ocular site. The main requirement of the present time is to develop novel drug delivery-backed stratagems to overcome the shortcomings of conventional formulations, which will reduce the morbidity associated with infectious keratitis and improve clinical outcomes. It is worth mentioning that there are documented incidents of Herpetic keratitis of the cornea followed by COVID-19 infection and vaccination. Conclusion: This paper is a rigorous review of all the novel drug delivery strategies to combat ocular keratitis. These future drug delivery strategies will pave the way for the present time researcher and formulation chemists to develop multi-dimensional novel formulations that are safe, patient-compliant, and surpass the ocular barriers to maintain therapeutic drug levels in ocular tissues.

Targeted Drug Delivery Strategies for the Treatment of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) ranks among the most prevalent malignant tumors, exhibiting a high incidence rate that presents a substantial threat to human health. The use of sorafenib and lenvatinib, commonly employed as single-agent targeted inhibitors, complicates the treatment process due to the absence of definitive targeting. Nevertheless, the advent of nanotechnology has injected new optimism into the domain of liver cancer therapy. Nanocarriers equipped with active targeting or passive targeting mechanisms have demonstrated the capability to deliver drugs to tumor cells with high efficiency. This approach not only facilitates precise delivery to the affected site but also enables targeted drug release, thereby enhancing therapeutic efficacy. As medical technology progresses, there is an increasing call for innovative treatment modalities, including novel chemotherapeutic agents, gene therapy, phototherapy, immunotherapy, and combinatorial treatments for HCC. These emerging therapies are anticipated to yield improved clinical outcomes for patients, while minimizing systemic toxicity and adverse effects. Consequently, the application of nanotechnology is poised to significantly improve HCC treatment. This review focused on targeted strategies for HCC and the application of nanotechnology in this area.

Leukemia Cell Hitchhiking Hypoxia Responsive Nanogel for Improved Immunotherapy of Acute Myeloid Leukemia

AbstractImmune checkpoint blockade (ICB) with anti‐CD47 antibodies (aCD47) is a promising therapeutic approach that has the potential to revolutionize the treatment of acute myeloid leukemia (AML). However, the low immune response rate and high systemic hematotoxicity remain substantial barriers to its success in clinical AML treatment. A synthetic protein nanogel formulation of aCD47 and resiquimod (R848) (termed CR‐TNG) is developed that targets TIM‐3 on the surface of leukemia cells. Upon intravenous injection, the CR‐TNG efficiently conjugates onto the blood‐circulating leukemia cells and migrates toward the bone marrow (BM) by exploiting the natural BM homing capability of leukemia cells. CR‐TNG releases aCD47 and R848 in a bone marrow hypoxic microenvironment, which significantly induces immunosuppression and enhances the anti‐leukemia immune response by activating macrophage “eat me” signaling and priming myeloid macrophages in the BM niche. These findings provide a leukemia cell‐hitchhiking drug delivery strategy that addresses both systemic hematotoxicity and low immune response rate in AML.

Revealing the pH-dependent conformational changes in sol g 2.1 protein and potential ligands binding

Sol g 2, a major protein found in the venom of the tropical fire ant (Solenopsis geminata), is well-known for its ability to bind various hydrophobic molecules. In this study, we investigate the binding activity of recombinant Sol g 2.1 protein (rSol g 2.1) with potential molecules, including (E)-β-Farnesene, α-Caryophyllene, and 1-Octen-3-ol at different pH levels (pH 7.4 and 5.5) using fluorescence competitive binding assays (FCBA). Our results revealed that Sol g 2.1 protein has higher affinity binding with these ligands at neutral pH. Relevance to molecular docking and molecular dynamics simulations were utilized to provide insights into the stability and conformational dynamics of Sol g 2.1 and its ligand complexes. After simulation, we found that Sol g 2.1 protein has higher affinity binding with these ligands as well as high structural stability at pH 7.4 than at an acidic pH level, indicating by RMSD, RMSF, Rg, SASA, and principal component analysis (PCA). Additionally, the Sol g 2.1 protein complexes at pH 7.4 showed significantly lower binding free energy (∆Gbind) and higher total residue contributions, particularly from key non-polar amino acids such as Trp36, Met40, Cys62, and Ile104, compared to the lower pH environment. These explain why they exhibited higher binding affinity than the lower pH. Therefore, we suggested that Sol g 2.1 protein is a pH-responsive carrier protein. These findings also expand our understanding of protein–ligand interactions and offer potential avenues for the development of innovative drug delivery strategies targeting Sol g 2.1 protein.