Zinc Oxide/Carbon Material-Embedded Supramolecular Drug Delivery System with Photoswitching Properties for Highly Selective and Effective Chemotherapy.

Phototherapy has become a hopeful procedure for the treatment of cancer. Nevertheless, the straightforward creation of a theranostic system that can achieve both tumor localization and production of oxygen species is greatly desired yet remains a challenging endeavor. In this study, we synthesized spherical nanostructures by decorating zinc oxide (ZnO) with peanut shell-based carbon (PNS-C) in an aqueous solution. The PNS-C-decorated ZnO (ZnO/PNS-C)-embedded supramolecular system exhibited spontaneous self-assembly. The nanogels that are produced have several desirable characteristics, including exceptional resistance to degradation by light, highly stable nanostructures that form spontaneously in biological environments, outstanding ability to prevent the destruction of red blood cells, and a high level of sensitivity to changes in pH and light. Under light irradiation, the addition of ZnO/PNS-C-incorporated supramolecular provided high reactive oxygen species production. Moreover, in vitro cellular assays demonstrated ZnO/PNS-C-incorporated supramolecular exhibited highly selective and induced phototoxicity into cancer cells and no effect on the viability of normal cells both before and after irradiation. Overall, the ZnO/PNS-C-incorporated supramolecular system has the potential to stimulate advancements in phototherapy by utilizing highly tumor-selective therapeutic molecules. This can lead to a more effective targeted therapy for cancers.

Synthesis, characterization and stability of crosslinked chitosan-maltodextrin pH-sensitive nanogels.

Polysaccharide-based nanogels offer a wide range of chemical compositions and are of great interest due to their biodegradability, biocompatibility, non-toxicity, and their ability to display pH, temperature, or enzymatic response. In this work, we synthesized monodisperse and tunable pH-sensitive nanogels by crosslinking, through reductive amination, chitosan and partially oxidized maltodextrins, by keeping the concentration of chitosan around the overlap concentration, i.e. in the dilute and semi-dilute regime. The chitosan/maltodextrin nanogels presented sizes ranging from 63 ±â€¯9 to 279 ±â€¯16 nm, showed quasi-spherical and cauliflower-like morphology, reached a ζ-potential of +36 ±â€¯2 mV and maintained a colloidal stability for up to 7 weeks. It was found that the size and surface charge of nanogels depended both on the oxidation degree of maltodextrins and chitosan concentration, as well as on its degree of acetylation and protonation, the latter tuned by pH. The pH-responsiveness of the nanogels was evidenced by an increased size, owed to swelling, and ζ-potential when pH was lowered. Finally, maltodextrin-chitosan biocompatible nanogels were assessed by cell viability assay performed using the HEK293T cell line.

Hybrid Nanogel Drug Delivery Systems: Transforming the Tumor Microenvironment through Tumor Tissue Editing.

The future of drug delivery offers immense potential for the creation of nanoplatforms based on nanogels. Nanogels present a significant possibility for pharmaceutical advancements because of their excellent stability and effective drug-loading capability for both hydrophobic and hydrophilic agents. As multifunctional systems, composite nanogels demonstrate the capacity to carry genes, drugs, and diagnostic agents while offering a perfect platform for theranostic multimodal applications. Nanogels can achieve diverse responsiveness and enable the stimuli-responsive release of chemo-/immunotherapy drugs and thus reprogramming cells within the TME in order to inhibit tumor proliferation, progression, and metastasis. In order to achieve active targeting and boost drug accumulation at target sites, particular ligands can be added to nanogels to improve the therapeutic outcomes and enhance the precision of cancer therapy. Modern "immune-specific" nanogels also have extra sophisticated tumor tissue-editing properties. Consequently, the introduction of a multifunctional nanogel-based drug delivery system improves the targeted distribution of immunotherapy drugs and combinational therapeutic treatments, thereby increasing the effectiveness of tumor therapy.

Cyclodextrin-based supramolecular nanogels decorated with mannose for short peptide encapsulation.

Nanogels are aqueous dispersions of hydrogel particles formed by physically or chemically cross-linked polymer networks of nanoscale size. Herein, we devised a straightforward technique to fabricate a novel class of physically cross-linked nanogels via a self-assembly process in water involving α-cyclodextrin and a mannose molecule that was hydrophobically modified using an alkyl chain. The alkyl chain-modified mannose was synthesized in five steps, starting with D-mannose. Subsequently, nanogels were formed by subjecting α-cyclodextrin and the hydrophobically modified mannose to magnetic stirring in water. By adjusting the mole ratio between the hydrophobically modified mannose and α-cyclodextrin, nanogels with an average 100-150 nm diameter were obtained. Physicochemical and structural analyses by 1H NMR and X-ray diffraction unveiled a supramolecular and hierarchical mechanism underlying the creation of these nanogels. The proposed mechanism of nanogel formation involves two distinct steps: initial interaction of hydrophobically modified mannose with α-cyclodextrin resulting in the formation of inclusion complexes, followed by supramolecular interactions among these complexes, ultimately leading to nanogel formation after 72 h of stirring. We demonstrated the nanogels' ability to encapsulate a short peptide ([p-tBuF2, R5]SHf) as a water-soluble drug model. This discovery holds promise for potentially utilizing these nanogels in drug delivery applications.

Design and applications of polymer-like peptides in biomedical nanogels.

INTRODUCTION: Polymer nanogels are among the most promising nanoplatforms for use in biomedical applications. The substantial interest for these drug carriers is to enhance the transportation of bioactive substances, reduce the side effects, and achieve optimal action on the curative sites by targeting delivery and triggering the release of the drugs in a controlled and continuous mode. AREA COVERED: The review discusses the opportunities, applications, and challenges of synthetic polypeptide nanogels in biomedicine, with an emphasis on the recent progress in cancer therapy. It is evidenced by the development of polypeptide nanogels for better controlled drug delivery and release, in complex in vivo microenvironments in biomedical applications. EXPERT OPINION: Polypeptide nanogels can be developed by choosing the amino acids from the peptide structure that are suitable for the type of application. Using a stimulus - sensitive peptide nanogel, it is possible to obtain the appropriate transport and release of the drug, as well as to achieve desirable therapeutic effects, including safety, specificity, and efficiency. The final system represents an innovative way for local and sustained drug delivery at a specific site of the body.

An antibacterial, multifunctional nanogel for efficient treatment of neutrophilic asthma.

Asthma is a chronic and heterogeneous disease affecting the lungs and respiratory tract. In particular, the neutrophil subtype of asthma was described as persistent, more severe, and corticosteroid-resistant. Growing evidence suggested that nontypeable Haemophilus influenzae (NTHi) infection contributes to the development of neutrophilic asthma, exacerbating clinical symptoms and increasing the associated medical burden. In this work, arginine-grafted chitosan (CS-Arg) was ionically cross-linked with tris(2-carboxyethyl) phosphine (TCEP), and a highly-efficient antimicrobial agent, poly-ε-L-Lysine (ε-PLL), was incorporated to prepare ε-PLL/CS-Arg/TCEP (ECAT) composite nanogels. The results showed that ECAT nanogels exhibited highly effective inhibition against the proliferation of NTHi, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). In addition, ECAT nanogels could effectively inhibit the formation of mucins aggregates in vitro, suggesting that the nanogel might have the potential to destroy mucin in respiratory disease. Furthermore, in the ovalbumin (OVA)/NTHi-induced Balb/c mice model of neutrophilic asthma, the number of neutrophils in the alveolar lavage fluid and the percentage of inflammatory cells in the blood were effectively reduced by exposure to tower nebulized administration of ECAT nanogels, and reversing airway hyperresponsiveness (AHR) and reducing inflammation in neutrophilic asthma mice. In conclusion, the construction of ECAT nanogels was a feasible anti-infective and anti-inflammatory therapeutic strategy, which demonstrated strong potential in the clinical treatment of neutrophilic asthma.

Beyond the Charge: Interplay of Nanogels' Functional Group and Zeta-Potential for Antifungal Drug Delivery to Human Pathogenic Fungus Aspergillus fumigatus.

The ubiquitous mold Aspergillus fumigatus (A. fumigatus) is one of the main fungal pathogens causing invasive infections in immunocompromised humans. Conventional antifungal agents exhibit limited efficacy and often cause severe side effects. Nanoparticle-based antifungal delivery provides a promising alternative, which can increase local drug concentration while mitigating toxicity, thereby enhancing treatment efficacy. Previous research underscores the potential of poly(glycidol)-based nanogels (NG) with negative surface charge as carriers for delivering antifungals to A. fumigatus hyphae. In this study, we tailored NG with 2-carboxyethyl acrylate (CEA) or with phosphoric acid 2-hydroxyethyl acrylate (PHA). We discovered that quenching with PHA clearly improved the adhesion of NG to hyphal surface and the internalization of NG into the hyphae under protein-rich conditions, surpassing the outcomes of non-quenched and CEA-quenched NG. This enhancement cannot be solely attributed to an increase in negative surface charge but appears to be contingent on the functional group of the quencher. Furthermore, we demonstrate that itraconazole-loaded, PHA-functionalized nanogels (NGxPHA-ITZ) showed lower MIC in vitro and superior therapeutic effect in vivo against A. fumigatus compared to pure itraconazole. This confirms NGxPHA as a promising antifungal delivery system. This article is protected by copyright. All rights reserved.

Molecularly imprinted nanogels as synthetic recognition materials for the ultrasensitive detection of periodontal disease biomarkers.

Periodontal disease affects supporting dental structures and ranks among one of the top most expensive conditions to treat in the world. Moreover, in recent years, the disease has also been linked to cardiovascular and Alzheimer's diseases. At present, there is a serious lack of accurate diagnostic tools to identify people at severe risk of periodontal disease progression. Porphyromonas gingivalis is often considered one of the most contributing factors towards disease progression. It produces the Arg- and Lys-specific proteases Rgp and Kgp, respectively. Within this work, a short epitope sequence of these proteases is immobilised onto a magnetic nanoparticle platform. These are then used as a template to produce high-affinity, selective molecularly imprinted nanogels, using the common monomers N-tert-butylacrylamide (TBAM), N-isopropyl acrylamide (NIPAM), and N-(3-aminopropyl) methacrylamide hydrochloride (APMA). N,N-Methylene bis(acrylamide) (BIS) was used as a crosslinking monomer to form the interconnected polymeric network. The produced nanogels were immobilised onto a planar gold surface and characterised using the optical technique of surface plasmon resonance. They showed high selectivity and affinity towards their template, with affinity constants of 79.4 and 89.7 nM for the Rgp and Kgp epitope nanogels, respectively. From their calibration curves, the theoretical limit of detection was determined to be 1.27 nM for the Rgp nanogels and 2.00 nM for the Kgp nanogels. Furthermore, they also showed excellent selectivity against bacterial culture supernatants E8 (Rgp knockout), K1A (Kgp knockout), and W50-d (wild-type) strains in complex medium of brain heart infusion (BHI).

Rational Design of Highly Selective Sialyllactose-Imprinted Nanogels.

We describe a facile method to prepare water-compatible molecularly imprinted polymer nanogels (MIP NGs) as synthetic antibodies against target glycans. Three different phenylboronic acid (PBA) derivatives were explored as monomers for the synthesis of MIP NGs targeting either α2,6- or α2,3-sialyllactose, taken as oversimplified models of cancer-related sT and sTn antigens. Starting from commercially available 3-acrylamidophenylboronic acid, also its 2-substituted isomer and the 5-acrylamido-2-hydroxymethyl cyclic PBA monoester derivative were initially evaluated by NMR studies. Then, a small library of MIP NGs imprinted with the α2,6-linked template was synthesized and tested by mobility shift Affinity Capillary Electrophoresis (msACE) to rapidly assess an affinity ranking. Finally, the best monomer o-acrylamido PBA was selected for the synthesis of polymers targeting both sialyllactoses. The resulting MIP NGs display an affinity constant ≈ 106 M-1 and selectivity towards imprinted glycans. This general procedure could be applied to any non-modified carbohydrate template possessing a reducing end.

Ultrasound-targeted microbubble destruction improves the suppression and magnetic resonance imaging of pancreatic cancer with polyethyleneimine nanogels.

The chemoresistance of pancreatic cancer tumors urgently needs to be addressed. Pancreatic cancer is characterized by an abundant stroma, with significant fibrous connective tissue formation that encapsulates the tumor parenchyma and forms an interstitial microenvironment. Pancreatic stellate cells (PSCs) play a crucial role in this microenvironment and specially secrete periosteal protein (periostin), which can promote tumor growth, metastasis, and chemoresistance. Therefore, periostin has become a specific target of chemotherapy resistance intervention methods. The proposed polyethyleneimine (PEI) nanogels have multiple modification and efficient drug-loading properties. Additionally, ultrasound-targeted microbubble destruction (UTMD) supports the breakdown of the tough interstitial barrier of pancreatic cancer. A small interfering RNA (siRNA) can be used to downregulated the periostin gene, while sustained release of gemcitabine can promote killing of tumor cells. This method achieves a combination of gene silencing and chemotherapy. The imaging effect can be evaluated using magnetic resonance imaging (MRI). The ultimate goal of this work is to support individualized and effective therapeutic methods and help develop new strategies for pancreatic cancer treatment.

Using RAFT Polymerization Methodologies to Create Branched and Nanogel-Type Copolymers.

This review aims to highlight the most recent advances in the field of the synthesis of branched copolymers and nanogels using reversible addition-fragmentation chain transfer (RAFT) polymerization. RAFT polymerization is a reversible deactivation radical polymerization technique (RDRP) that has gained tremendous attention due to its versatility, compatibility with a plethora of functional monomers, and mild polymerization conditions. These parameters lead to final polymers with good control over the molar mass and narrow molar mass distributions. Branched polymers can be defined as the incorporation of secondary polymer chains to a primary backbone, resulting in a wide range of complex macromolecular architectures, like star-shaped, graft, and hyperbranched polymers and nanogels. These subcategories will be discussed in detail in this review in terms of synthesis routes and properties, mainly in solutions.

An Investigation into the Effects of Processing Factors on the Properties and Scaling-Up Potential of Propranolol-Loaded Chitosan Nanogels.

Chitosan-triphosphate (TPP) nanogels are widely studied drug delivery carrier systems, typically prepared via a simple mixing process. However, the effects of the processing factors on nanogel production have not been extensively explored, despite the importance of understanding and standardising such factors to allow upscaling and commercial usage. This study aims to systematically evaluate the effects of various fabrication and processing factors on the properties of nanogels using a Design of Experiment approach. Hydrodynamic size, polydispersity index (PDI), zeta potential, and encapsulation efficiency were determined as the dependent factors. The temperature, stirring rate, chitosan grade, crosslinker choice, and the interaction term between temperature and chitosan grade were found to have a significant effect on the particle size, whereas the effect of temperature and the addition rate of crosslinker on the PDI was also noteworthy. Moreover, the addition rate of the crosslinker and the volume of the reaction vessel were found to impact the encapsulation efficiency. The zeta potential of the nanogels was found to be governed by the chitosan grade. The optimal fabrication conditions for the development of medium molecular weight chitosan and TPP nanogels included the following: the addition rate for TPP solution was set at 2 mL/min, while the solution was then stirred at a temperature of 50 °C and a stirring speed of 600 rpm. The volume of the glass vial used was 28 mL, while the stirrer size was 20 mm. The second aim of the study was to evaluate the potential for scaling up the nanogels. Size and PDI were found to increase from 128 nm to 151 nm and from 0.232 to 0.267, respectively, when the volume of the reaction mixture was increased from 4 to 20 mL and other processing factors were kept unchanged. These results indicate that caution is required when scaling up as the nanogel properties may be significantly altered with an increasing production scale.

Utilizing stem cell-secreted molecules as a versatile toolbox for skin regenerative medicine.

Stem cells are recognized as an important target and tool in regenerative engineering. In this study, we explored the feasibility of engineering amniotic fluid-derived mesenchymal stem cell-secreted molecules (afMSC-SMs) as a versatile bioactive material for skin regenerative medicine applications in a time- and cost-efficient and straightforward manner. afMSC-SMs, obtained in powder form through ethanol precipitation, effectively contributed to preserving the self-renewal capacity and differentiation potential of primary human keratinocytes (pKCs) in a xeno-free environment, offering a potential alternative to traditional culture methods for their long-term in vitro expansion, and allowed them to reconstitute a fully stratified epithelium sheet on human dermal fibroblasts. Furthermore, we demonstrated the flexibility of afMSC-SMs in wound healing and hair regrowth through injectable hydrogel and nanogel-mediated transdermal delivery systems, respectively, expanding the pool of regenerative applications. This cell-free approach may offer several potential advantages, including streamlined manufacturing processes, scalability, controlled formulation, longer shelf lives, and mitigation of risks associated with living cell transplantation. Accordingly, afMSC-SMs could serve as a promising therapeutic toolbox for advancing cell-free regenerative medicine, simplifying their broad applicability in various clinical settings.

Curcumin Nanogel Preparations: A Promising Alternative for Psoriasis Treatment.

Curcumin is a naturally occurring polyphenolic compound extracted from the rhizomes of Curcuma longa, commonly known as turmeric. It has been used for centuries in traditional medicine and is gaining increasing attention in modern medicine owing to its potential therapeutic benefits. Psoriasis is a chronic inflammatory disease characterized by red scaly patches on the skin. Curcumin has been found to be effective in treating psoriasis by inhibiting the activity of various enzymes and proteins involved in the inflammation and proliferation of psoriatic skin cells. Nanogel preparation of curcumin has been found to be a promising approach for the delivery of compounds to treat psoriasis. Nanogels are composed of biocompatible and biodegradable crosslinked hydrogels. The nanogel formulation of curcumin increases its solubility, stability, and bioavailability, indicating that a lower dose is needed to achieve the same therapeutic effect. This review article suggests that the nanogel preparation of curcumin can be a better alternative for psoriasis treatment as it increases the bioavailability and stability of curcumin and also reduces the required dosage. This study suggests that curcumin nanogel preparations are promising alternatives to traditional psoriasis treatments and could potentially be used as a more effective and safe treatment option. This article highlights the need for further research to fully understand the potential of curcumin nanogel preparations for psoriasis treatment in humans.

Biomimetic Dual-Target Theranostic Nanovaccine Enables Magnetic Resonance Imaging and Chemo/Chemodynamic/Immune Therapy of Glioma.

Development of theranostic nanomedicines to tackle glioma remains to be challenging. Here, we present an advanced blood-brain barrier (BBB)-crossing nanovaccine based on cancer cell membrane-camouflaged poly(N-vinylcaprolactam) (PVCL) nanogels (NGs) incorporated with MnO2 and doxorubicin (DOX). We show that the disulfide bond-cross-linked redox-responsive PVCL NGs can be functionalized with dermorphin and imiquimod R837 through cell membrane functionalization. The formed functionalized PVCL NGs having a size of 220 nm are stable, can deplete glutathione, and responsively release both Mn2+ and DOX under the simulated tumor microenvironment to exert the chemo/chemodynamic therapy mediated by DOX and Mn2+, respectively. The combined therapy induces tumor immunogenic cell death to maturate dendritic cells (DCs) and activate tumor-killing T cells. Further, the nanovaccine composed of cancer cell membranes as tumor antigens, R837 as an adjuvant with abilities of DC maturation and macrophages M1 repolarization, and MnO2 with Mn2+-mediated stimulator of interferon gene activation of tumor cells can effectively act on both targets of tumor cells and immune cells. With the dermorphin-mediated BBB crossing, cell membrane-mediated homologous tumor targeting, and Mn2+-facilitated magnetic resonance (MR) imaging property, the designed NG-based theranostic nanovaccine enables MR imaging and combination chemo-, chemodynamic-, and imnune therapy of orthotopic glioma with a significantly decreased recurrence rate.

Polyglycerol-Functionalized ß-Cyclodextrins as Crosslinkers in Thermoresponsive Nanogels for the Enhanced Dermal Penetration of Hydrophobic Drugs.

Thermoresponsive nanogels (tNGs) are promising candidates for dermal drug delivery. However, poor incorporation of hydrophobic drugs into hydrophilic tNGs limits the therapeutic efficiency. To address this challenge, ß-cyclodextrins (ß-CD) are functionalized by hyperbranched polyglycerol serving as crosslinkers (hPG-ßCD) to fabricate ßCD-tNGs. This novel construct exhibits augmented encapsulation of hydrophobic drugs, shows the appropriate thermal response to dermal administration, and enhances the dermal penetration of payloads. The structural influences on the encapsulation capacity of ßCD-tNGs for hydrophobic drugs are analyzed, while concurrently retaining their efficacy as skin penetration enhancers. Various synthetic parameters are considered, encompassing the acrylation degree and molecular weight of hPG-ßCD, as well as the monomer composition of ßCD-tNGs. The outcome reveals that ßCD-tNGs substantially enhance the aqueous solubility of Nile Red elevating to 120 µg mL-1 and augmenting its dermal penetration up to 3.33 µg cm-2. Notably, the acrylation degree of hPG-ßCD plays a significant role in dermal drug penetration, primarily attributed to the impact on the rigidity and hydrophilicity of ßCD-tNGs. Taken together, the introduction of the functionalized ß-CD as the crosslinker in tNGs presents a novel avenue to enhance the efficacy of hydrophobic drugs in dermatological applications, thereby offering promising opportunities for boosted therapeutic outcomes.

Antibody-Conjugated Nanogel with Two Immune Checkpoint Inhibitors for Enhanced Cancer Immunotherapy.

Cancer immunotherapy by immune checkpoint inhibitors (ICIs) acts on antitumor responses by stimulating the immune system to attack cancer cells. However, this powerful therapy is hampered by its high treatment cost and limited efficacy. Here, it is shown that the development of an antibody-conjugated nanogel (ANGel), consisting of N-isopropylacrylamide-co-acrylic acid and antibody-binding protein (protein A), potentiates the efficacy of two ICI monoclonal antibodies (mAbs) (cytotoxic-T-lymphocyte-associated antigen 4 and programmed death ligand-1 mAbs). Compared with mAb treatment alone, treatment with a bispecific ANGel surface-conjugated with the mAbs significantly decreases both the survival of Michigan Cancer Foundation-7 (MCF-7) and M D Anderson-Metastatic Breast-231 (MDA-MB-231) breast cancer cells in vitro and the burden of 4T1-luciferase-2-derived orthotopic syngeneic tumors in vivo. The bispecific ANGel is also more potent than the conventional treatment at prolonging survival in animals with triple-negative breast cancer. The advantage of the bispecific ANGel over other engineered bispecific antibodies arises not only from the adaptability to link multiple antibodies quickly and easily, but also from the capability to maintain the anticancer effect steadily at subcutaneously delivered tumor site. This finding has an important implication for cancer immunotherapy, opening a new paradigm to treat solid tumors.

Nasal Delivery to the Brain: Harnessing Nanoparticles for Effective Drug Transport.

The nose-to-brain drug-delivery system has emerged as a promising strategy to overcome the challenges associated with conventional drug administration for central nervous system disorders. This emerging field is driven by the anatomical advantages of the nasal route, enabling the direct transport of drugs from the nasal cavity to the brain, thereby circumventing the blood-brain barrier. This review highlights the significance of the anatomical features of the nasal cavity, emphasizing its high permeability and rich blood supply that facilitate rapid drug absorption and onset of action, rendering it a promising domain for neurological therapeutics. Exploring recent developments and innovations in different nanocarriers such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, dendrimers, micelles, nanoemulsions, nanosuspensions, carbon nanotubes, mesoporous silica nanoparticles, and nanogels unveils their diverse functions in improving drug-delivery efficiency and targeting specificity within this system. To minimize the potential risk of nanoparticle-induced toxicity in the nasal mucosa, this article also delves into the latest advancements in the formulation strategies commonly involving surface modifications, incorporating cutting-edge materials, the adjustment of particle properties, and the development of novel formulations to improve drug stability, release kinetics, and targeting specificity. These approaches aim to enhance drug absorption while minimizing adverse effects. These strategies hold the potential to catalyze the advancement of safer and more efficient nose-to-brain drug-delivery systems, consequently revolutionizing treatments for neurological disorders. This review provides a valuable resource for researchers, clinicians, and pharmaceutical-industry professionals seeking to advance the development of effective and safe therapies for central nervous system disorders.

Fmoc-FF hydrogels and nanogels for improved and selective delivery of dexamethasone in leukemic cells and diagnostic applications.

Dexamethasone (DEX) is a synthetic analogue of cortisol commonly used for the treatment of different pathological conditions, comprising cancer, ocular disorders, and COVID-19 infection. Its clinical use is hampered by the low solubility and severe side effects due to its systemic administration. The capability of peptide-based nanosystems, like hydrogels (HGs) and nanogels (NGs), to serve as vehicles for the passive targeting of active pharmaceutical ingredients and the selective internalization into leukemic cells has here been demonstrated. Peptide based HGs loaded with DEX were formulated via the "solvent-switch" method, using Fmoc-FF homopeptide as building block. Due to the tight interaction of the drug with the peptidic matrix, a significant stiffening of the gel (G' = 67.9 kPa) was observed. The corresponding injectable NGs, obtained from the sub-micronization of the HG, in the presence of two stabilizing agents (SPAN®60 and TWEEN®60, 48/52 w/w), were found to be stable up to 90 days, with a mean diameter of 105 nm. NGs do not exhibit hemolytic effects on human serum, moreover they are selectively internalized by RS4;11 leukemic cells over healthy PBMCs, paving the way for the generation of new diagnostic strategies targeting onco-hematological diseases.