Delivery of proteins in plant cells can facilitate the design of desired functions by modulation of biological processes and plant traits but is currently limited by narrow host range, tissue damage, and poor scalability. Physical barriers in plants, including cell walls and membranes, limit protein delivery to desired plant tissues. Herein, a cationic high aspect ratio polymeric nanocarriers (PNCs) platform is developed to enable efficient protein delivery to plants. The cationic nature of PNCs binds proteins through electrostatic. The ability to precisely design PNCs\' size and aspect ratio allowed us to find a cutoff of ≈14 nm in the cell wall, below which cationic PNCs can autonomously overcome the barrier and carry their cargo into plant cells. To exploit these findings, a reduction-oxidation sensitive green fluorescent protein (roGFP) is deployed as a stress sensor protein cargo in a model plant Nicotiana benthamiana and common crop plants, including tomato and maize. In vivo imaging of PNC-roGFP enabled optical monitoring of plant response to wounding, biotic, and heat stressors. These results show that PNCs can be precisely designed below the size exclusion limit of cell walls to overcome current limitations in protein delivery to plants and facilitate species-independent plant engineering.

In recent years, development of biopolymeric nanofibers as an active biodegradable packaging system has attracted specific attention. The objective of this research was to develop zein-based electrospun nanofibers (NFs) incorporated with geraniol-loaded nanoliposomes (G-loaded NLPs). Geraniol was encapsulated into NLPs with an efficiency of 79.23%. The particle size and zeta potential of G-loaded NLPs were 121.50 nm and -38.30 mV, respectively. The successful loading of geraniol in the NLPs was approved by Fourier transform infrared (FT-IR) spectroscopy. The liposomal vesicles showed spherical shapes. G-loaded NLPs were added in the zein-based electrospun NFs at three different concentrations (0.25, 0.5, and 1%w/v). All NFs samples exhibited fibrillar structure. The increase of NLPs concentration enhanced the thermal stability of the NFs. However, the crystalline structure of zein NFs did not change by the addition of G-loaded NLPs. The highest surface hydrophobicity was related to the NFs containing 1% G-loaded NLPs. The mechanical parameters of NFs depend on the concentration of NLPs. The NFs incorporated with G-loaded NLPs showed inhibition activity against four foodborne pathogenic bacteria (Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Salmonella typhimurium) with an inhibition zone of 4.5-22 mm. Moreover, the α-diphenyl-β-picrylhydrazyl (DPPH) scavenging activity of NFs samples was located at the range of 20%-48%. These findings represent the Efficiency of the G-loaded NLPs for use as bioactive compound in the zein-based NFs as an active packaging material.

Personalized cancer vaccines targeting specific neoantigens have been envisioned as one of the most promising approaches in cancer immunotherapy. However, the physicochemical variability of the identified neoantigens limits their efficacy as well as vaccine manufacturing in a uniform format. Herein, we developed a uniform nanovaccine platform based on poly(2-oxazoline)s (POx) to chemically conjugate neoantigen peptides, regardless of their physicochemical properties. This vaccine system could self-assemble into nanoparticles with uniform size (around 50 nm) and improve antigen accumulation as well as infiltration in the lymph node to increase antigen presentation. In vivo vaccination using this system conjugated with three predicted peptide neoantigen peptides from the MC38 tumor cell line induced 100% robust CD8+ T cell responses and superior tumor clearance compared to free peptides. This POx-based vaccine carrier represents a generalizable approach to increase the availability and efficacy of screened neoantigen peptides for a personalized cancer vaccine.

Sphingolipids (SL) are well recognized for their cell signaling through extracellular and intracellular pathways. Based on chemistry different types of SL are biosynthesized in mammalian cells and have specific function in cellular activity. SL has an ampiphilic structure with have hydrophobic body attached to the polar head enables their use as a drug delivery agent in the form of nanocarriers. SL-based liposomes can improve the solubility of lipophilic drugs through host and drug complexes and are more stable than conventional liposomal formulations. Preclinical studies of SL nanocarriers are reported on topical delivery, oral delivery, ocular delivery, chemotherapeutic delivery, cardiovascular delivery and Alzheimer\'s disease. The commercial challenges and patents related to SL nanoformulations are highlighted in this article.
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Conventional chemotherapeutic approaches currently used for brain tumor treatment have low efficiency in targeted drug delivery and often have non-target toxicity. Development of stable and effective drug delivery vehicles for the most incurable diseases is one of the urgent biomedical challenges. We have developed polymer nanoparticles (NPs) with improved temozolomide (TMZ) delivery for promising brain tumor therapy, performing a rational design of polyelectrolyte complexes of oppositely charged polysaccharides of cationic chitosan and anionic pectin. The NPs\' diameter (30 to 330 nm) and zeta-potential (-29 to 73 mV) varied according to the initial mass ratios of the biopolymers. The evaluation of nanomechanical parameters of native NPs demonstrated changes in Young\'s modulus from 58 to 234 kPa and adhesion from -0.3 to -3.57 pN. Possible mechanisms of NPs\' formation preliminary based on ionic interactions between ionogenic functional groups were proposed by IR spectroscopy and dynamic rheology. The study of the parameters and kinetics of TMZ sorption made it possible to identify compounds that most effectively immobilize and release the active substance in model liquids that simulate the internal environment of the body. A polyelectrolyte carrier based on an equal ratio of pectin-chitosan (0.1% by weight) was selected as the most effective for the delivery of TMZ among a series of obtained NPs, which indicates a promising approach to the treatment of brain tumors.

Hepatocellular carcinoma (HCC) is a common malignant tumor originating from liver cells, characterized by complex pathogenesis and limited treatment options such as surgery, chemotherapy, and transplantation. Cisplatin, an effective chemotherapeutic agent, disrupts cancer cell DNA but is hindered by side effects and the need for controlled sustained release to optimize efficacy. Metal-organic frameworks (MOFs) have emerged as promising nanocarriers for precise local drug delivery, reducing required doses and mitigating side effects of chemotherapeutic drugs, thus offering a potential avenue for hepatocellular carcinoma (HCC) treatment. In this research, a rectangular channel MOF (Rumgay H, Ferlay J, Martel C, Georges D, Ibrahim AS, Zheng R, Wei W, Lemmens VEPP, Soerjomataram I (2022) Global, regional and national burden of primary liver cancer by subtype. Eur J Cancer 161:108-118) carrier was synthesized using ligand L as the organic linker coordinated with Cu(II) and I(I). The MOF\'s structure and fluorescence properties were characterized. Additionally, to enhance substrate biocompatibility, composite carrier materials were prepared by incorporating polylactic acid (PLA) with 1, utilized for cisplatin loading. To evaluate the inhibitory effect of PLA-1@cisplatin on HCC, HepG-2 and Huh-7 HCC cell lines were treated with varying concentrations of the drug for 48 h, and their cell viability was assessed. The results demonstrated a significant dose-dependent reduction in cell viability of both HepG-2 and Huh-7 cells. To explore the potential inhibitory mechanism of PLA-1@cisplatin on HCC, the mRNA levels of GADD45A and NACC1 in HepG-2 and Huh-7 cells post-treatment were measured. GADD45A expression, initially low in HCC cells, was significantly upregulated after drug treatment, while NACC1, typically highly expressed in HCC, showed a significant decrease in mRNA levels with increasing concentrations of PLA-1@cisplatin. These findings indicate that PLA-1@cisplatin effectively upregulates GADD45A expression and downregulates NACC1 expression. Overall, the developed cisplatin-loaded nanoparticle system holds promise for HCC treatment by reducing chemotherapy side effects and enhancing drug efficacy.

The research in nanotherapeutics is rapidly advancing, particularly in the realm of nanoconstructs for drug delivery. This study introduces folate-based carbon dot-decorated nanodroplets (f-Dnm), synthesized from a binary mixture of negatively charged folic acid carbon dots (f-CDs) and cationic-branched polyethylenimine (PEI). The uniformly spherical nanodroplets with an average diameter of 115 ± 15 nm exhibit notable photoluminescence. Surface potential analysis reveals a significant change upon coacervation, attributed to strong electrostatic interactions between f-CD and PEI. The engineered nanodroplets show excellent colloidal and photostability even after 6 months of storage at room temperature. The pH-dependent self-assembly and disassembly properties of f-Dnm are explored for drug loading and release studies using doxorubicin (DOX) as a model anticancer drug. Moreover, the f-Dnm nanocarrier demonstrates significantly higher drug loading capabilities (∼90%). In vitro release studies of doxorubicin-loaded f-Dnm [f-Dnm(DOX)] reveal 5 times higher drug release at lysosomal pH 5.4 compared to that at physiological blood pH 7.4. Cytocompatibility assessments using the MTT assay on HeLa, A549, and NIH-3T3 cells confirm the nontoxic nature of f-Dnm, even at high concentrations. Additionally, f-Dnm(DOX) exhibits higher cytotoxicity in HeLa cells compared to f-CD(DOX) at similar DOX concentrations. Cellular uptake studies show an increased uptake of f-Dnm in folate receptor-positive HeLa and MDA-MB 231 cells. Hemolysis assay validated the biocompatibility of the developed formulation. Overall, these engineered nanodroplets represent a class of nontoxic nanocarriers that offer promising potential as nanotherapeutics for folate receptor-positive cells.

Cancer immunotherapy has rapidly become the fourth mainstream treatment alternative after surgery, radiotherapy, and chemotherapy, with some promising results. It aims to kill tumor cells by mobilizing or stimulating cytotoxic immune cells. However, the clinical applications of tumor immunotherapies are limited owing to a lack of adequate delivery pathways and high toxicity. Recently, nanomaterials and genetic engineering have shown great potential in overcoming these limitations by protecting the delivery of antigens, activating targeted T cells, modulating the immunosuppressive tumor microenvironment, and improving the treatment efficacy. Bacillus Calmette-Guérin (BCG) is a live attenuated Mycobacterium bovis vaccine used to prevent tuberculosis, which was first reported to have antitumor activity in 1927. BCG therapy can activate the immune system by inducing various cytokines and chemokines, and its specific immune and inflammatory responses exert antitumor effects. BCG was first used during the 1970s as an intravesical treatment agent for bladder cancer, which effectively improved immune antitumor activity and prevented tumor recurrence. More recently, nano-BCG and genetically engineered BCG have been proposed as treatment alternatives for bladder cancer due to their ability to induce stronger and more stable immune responses. In this study, we outline the development of nano-BCG and genetically engineered BCG for bladder cancer immunotherapy and review their potential and associated challenges.
癌症免疫治疗已成为继手术、放疗和化疗之后的第四大主流治疗选择，并取得了令人鼓舞的成果。肿瘤免疫治疗通过调动或激发机体自身的免疫功能，从而抑制和杀伤肿瘤细胞。然而，肿瘤免疫治疗作为一种新兴的治疗手段，由于缺乏有效的免疫细胞传递途径以及具有较高的毒副作用，在临床上的应用受到限制。近年来，纳米材料和基因工程在保护抗原递送、激活靶向T细胞、调节免疫抑制的肿瘤微环境和提高治疗效果等方面显示出巨大的潜力。卡介苗是一种用于预防结核病的减毒牛分枝杆菌活疫苗，于1927年首次报道其抗肿瘤活性。卡介苗可通过诱导多种细胞因子和趋化因子激活免疫系统，其特异性免疫和炎症反应可发挥抗肿瘤作用。20世纪70年代，卡介苗首次作为治疗膀胱癌的膀胱灌注药物，有效地提高了免疫抗肿瘤活性，防止肿瘤复发。最近，纳米卡介苗和基因工程卡介苗因其能诱导更强且更稳定的免疫反应，被提出作为膀胱癌的治疗方案。在本研究中，我们概述了纳米卡介苗和基因工程卡介苗用于膀胱癌免疫治疗的发展，并回顾了它们的潜力和挑战。.

The deterioration in the structure of thyroid hormones causes many thyroid-related disorders, which leads to a negative effect on the quality of life, as well as the change in metabolic rate. For the treatment of thyroid disorders, daily use of levothyroxine-based medication is essential. In the study, it is aimed to develop a polymeric nanocarrier that can provide controlled drug release of levothyroxine. In this respect, the p(HEMA-MAGA) nanopolymer was synthesized and then characterized by Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and Zeta size analysis. The specific surface area of the nanopolymer was calculated as 587.68 m2/g. The pH, temperature, concentration, and time parameters were determined for levothyroxine binding to p(HEMA-MAGA) and optimum binding was determined as pH 7.4, 25 °C, 25 µg/mL concentration, and 30 min adsorption time. As a result of the release performed at pH 7.4, a release profile was observed which increased for the first 3 days and continued for 14 days. According to the results of MTT cell viability analysis, it was determined that the p(HEMA-MAGA) nanopolymeric carrier system had no cytotoxic effect. This developed polymer-based nanocarrier system is suitable for long-term and controlled release of levothyroxine. This is a unique and novel study in terms of developing poly hydroxyethylmethacrylate-co-methacryloyl glutamic acid-based polymeric nanoparticles for levothyroxine release.
Affinity-based nanoparticles were developed for long-term and controlled release of levothyroxine.p(HEMA-MAGA) nanopolymer was synthesized and characterized by Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and Zeta size analysis.Optimization studies of levothyroxine binding into p(HEMA-MAGA) nanopolymers were carried out and controlled release studies were made with loading in optimum parameters.MTT cell viability analysis were performed for determining that the p(HEMA-MAGA) nanopolymeric carrier system had no cytotoxic effect.

Cancer immunotherapy has rapidly become the fourth mainstream treatment alternative after surgery, radiotherapy, and chemotherapy, with some promising results. It aims to kill tumor cells by mobilizing or stimulating cytotoxic immune cells. However, the clinical applications of tumor immunotherapies are limited owing to a lack of adequate delivery pathways and high toxicity. Recently, nanomaterials and genetic engineering have shown great potential in overcoming these limitations by protecting the delivery of antigens, activating targeted T cells, modulating the immunosuppressive tumor microenvironment, and improving the treatment efficacy. Bacillus Calmette-Guérin (BCG) is a live attenuated Mycobacterium bovis vaccine used to prevent tuberculosis, which was first reported to have antitumor activity in 1927. BCG therapy can activate the immune system by inducing various cytokines and chemokines, and its specific immune and inflammatory responses exert antitumor effects. BCG was first used during the 1970s as an intravesical treatment agent for bladder cancer, which effectively improved immune antitumor activity and prevented tumor recurrence. More recently, nano-BCG and genetically engineered BCG have been proposed as treatment alternatives for bladder cancer due to their ability to induce stronger and more stable immune responses. In this study, we outline the development of nano-BCG and genetically engineered BCG for bladder cancer immunotherapy and review their potential and associated challenges.
癌症免疫治疗已成为继手术、放疗和化疗之后的第四大主流治疗选择，并取得了令人鼓舞的成果。肿瘤免疫治疗通过调动或激发机体自身的免疫功能，从而抑制和杀伤肿瘤细胞。然而，肿瘤免疫治疗作为一种新兴的治疗手段，由于缺乏有效的免疫细胞传递途径以及具有较高的毒副作用，在临床上的应用受到限制。近年来，纳米材料和基因工程在保护抗原递送、激活靶向T细胞、调节免疫抑制的肿瘤微环境和提高治疗效果等方面显示出巨大的潜力。卡介苗是一种用于预防结核病的减毒牛分枝杆菌活疫苗，于1927年首次报道其抗肿瘤活性。卡介苗可通过诱导多种细胞因子和趋化因子激活免疫系统，其特异性免疫和炎症反应可发挥抗肿瘤作用。20世纪70年代，卡介苗首次作为治疗膀胱癌的膀胱灌注药物，有效地提高了免疫抗肿瘤活性，防止肿瘤复发。最近，纳米卡介苗和基因工程卡介苗因其能诱导更强且更稳定的免疫反应，被提出作为膀胱癌的治疗方案。在本研究中，我们概述了纳米卡介苗和基因工程卡介苗用于膀胱癌免疫治疗的发展，并回顾了它们的潜力和挑战。.