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Abstract Background Lung cancer remains a leading cancer type, but current chemotherapy is limited by issues including poor drug delivery, toxicity, and resistance. To address these challenges, we developed a novel PLGA-PEG-LHRH (PPL) nanoconjugate system for improved drug delivery. Curcumin, known for its anticancer and P-gp inhibition properties, was co-loaded with bcl2siRNA (bclsR) to inhibit the bcl2 protein, thus overcoming both resistance mechanisms. Results The PPL conjugate was successfully synthesized and characterized using FTIR, 1H NMR, XRD, XPS and BCA assay. Curcumin and bclsR-loaded PLGA nanoemulsions were prepared by double emulsion solvent evaporation method and characterized. The optimized nanoconjugate had size of 179 ± 16 nm, favorable zeta potential, high drug entrapment, and was confirmed via TEM. Controlled release studies indicated 83% drug release within 24 h. In vitro studies revealed significant cytotoxicity against A549 lung cancer cells, with the nanoconjugate showing IC50 of 8.24 µg/mL compared to 21.26 µg/mL for plain curcumin. Enhanced cellular uptake and effective targeting of A549 cells were observed. Molecular analyses demonstrated significant downregulation of MDR1 and Bcl2 RNA and protein expression, highlighting the nanoconjugates' ability to suppress resistance mechanisms. Pharmacokinetic studies in Wistar rats showed superior plasma drug concentrations, half-life, and AUC for the nanoconjugate versus pure drug suspension. Biodistribution studies showed increased drug accumulation in the lungs. In vivo efficacy studies in Balb/c mice demonstrated higher tumor inhibition ratios for CUR-siRNA PPL NPs (66.89%) and CUR-PPL NPs (59.84%) which was further confirmed with TNFα and p53 levels in blood. Histopathological studies showed good healing in the CUR-siRNA PPL NP- and CUR-PPL NP-treated mice compared to suspension. Conclusion From the study, it may be concluded that the PPL nanoconjugate system, loaded with curcumin and bcsR, can be potentially effective, multifunctional targeted approach for lung cancer therapy. Graphical Abstract

Abstract The non-specificity of standard anticancer therapies has profound detrimental consequences in clinical treatment. Therapeutic specificity can be precisely achieved using cutting-edge ligands. Small synthetic oligonucleotide-ligands chosen through Systematic evolution of ligands by exponential enrichment (SELEX) would be an unceasing innovation in using nucleic acids as aptamers, frequently referred to as "chemical antibodies.” Aptamers act as externally controlled switching materials that can attach to various substrates, for example, membrane proteins or nucleic acid structures. Aptamers pose excellent specificity and affinity for target molecules and can be used as medicines to suppress tumor cell growth directly. The creation of aptamer-conjugated nanoconstructs has recently opened up innovative options in cancer therapy that are more effective and target tumor cells with minor toxicity to healthy tissues. This review focuses on a comprehensive description of the most capable classes of aptamer-tethered nanocarriers for precise recognition of cancer cells with significant development in proficiency, selectivity, and targetability for cancer therapy. Existing theranostic applications with the problems and future directions are also highlighted. Graphical Abstract

Abstract Background In the present study, the medicinal plants were exclusively selected based on their significant anti-HIV and anticancer activities. The green synthesis of gold nanoparticles was carried out using the 15 medicinal plant extracts on reduction with chloroauric acid. The present study also focused on a novel pharmacognostic approach over the usage of plants source. The nanoparticle synthesized through medicinal plants possessed the potential therapeutic properties of the plants. The resultant nanoparticle carried the attributes of a nanomaterial alongside the phytoactivity. Results Initially, individual nanoparticle (NP) was synthesized through a single plant extract and studied for its effective anti-HIV and anticancer activity. Finally, a nanoconjugate (NC) comprising of the 3 extracts (trio extract) in one nanoparticle was synthesized. The nanoparticles which exhibited comparatively high anti-HIV and anticancer activity were chosen for the synthesis of nanoconjugate, thereby achieving a synergistic anticancer and anti-HIV activity. Further, a nanodrug conjugate (NDC) was prepared in combination of AuNPs and the chemotherapeutic drug, doxorubicin (Dox) for cancer and AuNPs with antiretroviral drug azidothymidine (AZT) for HIV. Conclusions A nanodrug conjugate helps to enhance the efficiency of the drug. The nanodrug conjugate brings about a combinatorial effect of the nanomaterials and the drug. Further, a biocompatible nanocarrier was developed as a conjugate with chitosan and gold nanoparticles using STPP as gelating agent for the drug doxorubicin. The synthesis reaction was optimized under various underlying parameters. The gold nanoparticles proved to be stable at high temperature and different buffers and ensured to be a safe option for bioassays and in vivo applications. Upon storing the synthesized AuNPs at different storage conditions, the nanoparticles were observed to be highly stable for a period of more than 48 months. The present study resulted in biosynthesis of highly stable gold nanoparticles using medicinal plant extracts as reducing and stabilizing agents.

Advancing the development of the luminescent nanoprobes and conjugates toward the toxic analyte quantification plays a crucial role in environmental remedy. Cyanide ions (CN ^− ) play vital role in many industries, such as electroplating, mining, textiles, metallurgy, etc. The highly toxic CN ^− may be discharged into the environment. The presence of CN ^− in aquatic environment at micromolar level could lead to fatal issue in humans and living beings, which requires scrutiny to maintain the ecosystem. Thus, diverse probes, such as organic fluorophores, noble metal nanoparticles/clusters (NPs/NCs), carbon/graphene quantum dots (CQDs/GQDs), cadmium telluride/selenide quantum dots (CdTe QDs/CdSe QDs), cadmium/zinc/silver sulfide quantum dots (CdS QDs/ZnS QDs/ Ag _2 S QDs), etc, were proposed toward the quantification of CN ^− ions with real-time applications. Among them, the luminescent probes/conjugates derived from QDs, NPs, and NCs are unique and display astonishing selectivity and sensitivity to CN ^− . The observed luminescent responses can be attributed to agglomeration, inner filter effect (IFE), fluorescence resonance energy transfer (FRET), chemiluminescence resonance energy transfer (CRET), etc Till now there is no review article reporting the applications of the luminescent probes/conjugates derived from QDs, NPs, and NCs for CN ^− quantification. In this review, the employment of these probes/conjugates for detecting CN ^− is illustrated with detailed underlying mechanisms and real-time applications. Furthermore, the design requirements, advantages, limitations, and directions of the luminescent probes/conjugates are delivered for future studies.

The epidermal growth factor receptor (EGFR) is vital for many different types of cancer. Nimotuzumab (NmAb), an anti-EGFR monoclonal antibody (mAb), is used against some of EGFR-overexpressed cancers in various countries. It targets malignant cells and is internalized via receptor-mediated endocytosis. We hypothesized that mAb-nanoparticle conjugation would provide an enhanced therapeutic efficacy, and hence we conjugated NmAb with 27 nm spherical gold nanoparticles (AuNPs) to form AuNP-NmAb nanoconjugates. Using biophysical and spectroscopic methods, including ultraviolet-visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and Fourier-transform infrared spectroscopy (FTIR), the AuNP-NmAb complex was characterized. Furthermore, in vitro studies were performed using a medium-level EGFR-expressing skin cancer cell (A431, EGFRmedium) and low-level EGFR-expressing lung cancer cell (A549, EGFRlow) to evaluate anti-tumor and cellular uptake efficiency via MTT assay and single-particle inductively coupled plasma mass spectrometry (spICP-MS), respectively. In comparison to NmAb monotherapy, the AuNP-NmAb treatment drastically reduced cancer cell survivability: for A431 cells, the IC50 value of AuNP-NmAb conjugate was 142.7 µg/mL, while the IC50 value of free NmAb was 561.3 µg/mL. For A549 cells, the IC50 value of the AuNP-NmAb conjugate was 163.6 µg/mL, while the IC50 value of free NmAb was 1,082.0 µg/mL. Therefore, this study highlights the unique therapeutic potential of AuNP-NmAb in EGFR+ cancers and shows the potential to develop other mAb nanoparticle complexes for a superior therapeutic efficacy.

Abstract Background Neuroblastoma is the most common extracranial solid malignancy in childhood which, despite the current progress in radiotherapy and chemotherapy protocols, still has a high mortality rate in high risk tumors. Nanomedicine offers exciting and unexploited opportunities to overcome the shortcomings of conventional medicine. The photocatalytic properties of Fe3O4 core-TiO2 shell nanocomposites and their potential for cell specific targeting suggest that nanoconstructs produced using Fe3O4 core-TiO2 shell nanocomposites could be used to enhance radiation effects in neuroblastoma. In this study, we evaluated bare, metaiodobenzylguanidine (MIBG) and 3,4-Dihydroxyphenylacetic acid (DOPAC) coated Fe3O4@TiO2 as potential radiosensitizers for neuroblastoma in vitro. Results The uptake of bare and MIBG coated nanocomposites modestly sensitized neuroblastoma cells to ionizing radiation. Conversely, cells exposed to DOPAC coated nanocomposites exhibited a five-fold enhanced sensitivity to radiation, increased numbers of radiation induced DNA double-strand breaks, and apoptotic cell death. The addition of a peptide mimic of the epidermal growth factor (EGF) to nanoconjugates coated with MIBG altered their intracellular distribution. Cryo X-ray fluorescence microscopy tomography of frozen hydrated cells treated with these nanoconjugates revealed cytoplasmic as well as nuclear distribution of the nanoconstructs. Conclusions The intracellular distribution pattern of different nanoconjugates used in this study was different for different nanoconjugate surface molecules. Cells exposed to DOPAC covered nanoconjugates showed the smallest nanoconjugate uptake, with the most prominent pattern of large intracellular aggregates. Interestingly, cells treated with this nanoconjugate also showed the most pronounced radiosensitization effect in combination with the external beam x-ray irradiation. Further studies are necessary to evaluate mechanistic basis for this increased radiosensitization effect. Preliminary studies with the nanoparticles carrying an EGF mimicking peptide showed that this approach to targeting could perhaps be combined with a different approach to radiosensitization – use of nanoconjugates in combination with the radioactive iodine. Much additional work will be necessary in order to evaluate possible benefits of targeted nanoconjugates carrying radionuclides. Graphic abstract

Gene delivery has emerged as a promising alternative to conventional treatment approaches, allowing for the manipulation of gene expression through gene insertion, deletion, or alteration. However, the susceptibility of gene delivery components to degradation and challenges associated with cell penetration necessitate the use of delivery vehicles for effective functional gene delivery. Nanostructured vehicles, such as iron oxide nanoparticles (IONs) including magnetite nanoparticles (MNPs), have demonstrated significant potential for gene delivery applications due to their chemical versatility, biocompatibility, and strong magnetization. In this study, we developed an ION-based delivery vehicle capable of releasing linearized nucleic acids (tDNA) under reducing conditions in various cell cultures. As a proof of concept, we immobilized a CRISPR activation (CRISPRa) sequence to overexpress the pink1 gene on MNPs functionalized with polyethylene glycol (PEG), 3-[(2-aminoethyl)dithio]propionic acid (AEDP), and a translocating protein (OmpA). The nucleic sequence (tDNA) was modified to include a terminal thiol group and was conjugated to AEDP’s terminal thiol via a disulfide exchange reaction. Leveraging the natural sensitivity of the disulfide bridge, the cargo was released under reducing conditions. Physicochemical characterizations, including thermogravimetric analysis (TGA) and Fourier-transform infrared (FTIR) spectroscopy, confirmed the correct synthesis and functionalization of the MNP-based delivery carriers. The developed nanocarriers exhibited remarkable biocompatibility, as demonstrated by the hemocompatibility, platelet aggregation, and cytocompatibility assays using primary human astrocytes, rodent astrocytes, and human fibroblast cells. Furthermore, the nanocarriers enabled efficient cargo penetration, uptake, and endosomal escape, with minimal nucleofection. A preliminary functionality test using RT-qPCR revealed that the vehicle facilitated the timely release of CRISPRa vectors, resulting in a remarkable 130-fold overexpression of pink1. We demonstrate the potential of the developed ION-based nanocarrier as a versatile and promising gene delivery vehicle with potential applications in gene therapy. The developed nanocarrier is capable of delivering any nucleic sequence (up to 8.2 kb) once it is thiolated using the methodology explained in this study. To our knowledge, this represents the first MNP-based nanocarrier capable of delivering nucleic sequences under specific reducing conditions while preserving functionality.

Here we report the phycosynthesis of silver nanoparticles (Ag-NPs), using Codium capitatum extract, and the synthesis of fungal chitosan nanoparticles (FC-NPs), using extracted chitosan from Aspergillus niger mycelia. Then nanoconjugates from FC/Ag-NPs were produced and evaluated. The synthesized NPs had mean particles’ size diameters of 37.2, 68.4 and 79.6 nm for Ag-NPs, FC-NPs and FC/Ag-NPs, respectively. The FTIR (Fourier-transform infrared spectroscopy) analysis of synthesized NPs indicated their cross-linkage and interaction. The antibacterial activity of each type of NPs was assayed against drug resistant pathogens of Salmonella Typhimurium and Staphylococcus aureus. All NPs had powerful inhibitory effect and FC/Ag nanoconjugates had stronger activity than the other types. Scanning micrographs of FC/Ag-NPs treated S. Typhimurium elucidated vigorous alterations in cell surfaces and lethal damage to bacterial structure after 8 h of treatment. The nanoconjugates form FC-NPs and Ag-NPs had minute particle size with increasing bioactivity as antimicrobial agents to control drug resistant bacterial pathogens, which recommends their further exploration for topical applications in biomedical sectors.

Despite rapid advances in diagnostic and treatment approaches, the overall survival rate of cancer has not been improved. Colorectal cancer (CRC) is recognized as the third leading cause of neoplasm-related deaths worldwide, in large part due to its considerable metastasis and drug resistance. For developing new anticancer strategies, rapid progression of multimodal nanomedicines and nanoconjugates has provided promising treatment modalities for effective therapy of cancer. The limitations of cancer chemotherapy might be overcome through the use of such nanosized therapeutics, including nanoconjugates of monoclonal antibodies (mAbs) along with drugs and organic/inorganic nanoparticles. CRC cells express various molecular markers against which mAbs can be designed and used as targeting/therapeutic agents. This editorial highlights the importance of such targeted nanosystems against CRC.

The protection of current influenza vaccines is limited due to the viral antigenic shifts and antigenic drifts. The universal influenza vaccine is a new hotspot in vaccine research that aims to overcome these problems. Polydopamine (PDA), a versatile biomaterial, has the advantages of an excellent biocompatibility, controllable particle size, and distinctive drug loading approach in drug delivery systems. To enhance the immunogenicities and delivery efficiencies of H9N2 avian influenza virus (AIV) epitope peptide vaccines, PDA nanoparticles conjugated with the BPP-V and BP-IV epitope peptides were used to prepare the nano BPP-V and BP-IV epitope peptide vaccines, respectively. The characteristics of the newly developed epitope peptide vaccines were then evaluated, revealing particle sizes ranging from approximately 240 to 290 nm (PDI

Green synthesis of silver nanoparticles (AgNPs) was synthesized from fresh garlic extract coupled with isoniazid hydrazide (INH), a commonly used antibiotic to treat tuberculosis. A molecular docking study conducted with the selected compounds compared with anthranilate phosphoribosyltransferase (trpD) from Mycobacterium tuberculosis. The aqueous extract of garlic was prepared and mixed with silver nitrate (AgNO3) solution for the superfast synthesis of stable AgNPs. INH was then conjugated with AgNPs at different ratios (v/v) to obtain stable INH-AgNPs conjugates (AgNCs). The resulting AgNCs characterized by FTIR spectra revealed the ultrafast formation of AgNPs (

Immune checkpoint receptor signaling pathways constitute a prominent class of “immune synapse,” a cell-to-cell connection that represses T-lymphocyte effector functions. As a possible evolutionary countermeasure against autoimmunity, this strategy is aimed at lowering potential injury to uninfected cells in infected tissues and at minimizing systemic inflammation. Nevertheless, tumors can make use of these strategies to escape immune recognition, and consequently, such mechanisms represent chances for immunotherapy intervention. Recent years have witnessed the advance of pharmaceutical nanotechnology, or nanomedicine, as a possible strategy to ameliorate immunotherapy technical weaknesses thanks to its intrinsic biophysical properties and multifunctional modifying capability. To improve the long-lasting response rate of checkpoint blockade therapy, nanotechnology has been employed at first for the delivery of single checkpoint inhibitors. Further, while therapy via single immune checkpoint blockade determines resistance and a restricted period of response, strong interest has been raised to efficiently deliver immunomodulators targeting different inhibitory pathways or both inhibitory and costimulatory pathways. In this review, the partially explored promise in implementation of nanotechnology to improve the success of immune checkpoint therapy and solve the limitations of single immune checkpoint inhibitors is debated. We first present the fundamental elements of the immune checkpoint pathways and then outline recent promising results of immune checkpoint blockade therapy in combination with nanotechnology delivery systems.

The aim of this study was to develop drug delivery nanosystems based on pegylated gold nanoparticles (PEGAuNPs) for a combination against pancreatic cancer cells. Doxorubicin and varlitinib, an anthracycline and a tyrosine kinase inhibitor respectively, were conjugated with gold nanoparticles. The systems were characterized, after synthesis, regarding their size, stability and morphology. An efficient conjugation of doxorubicin and varlitinib with PEGAuNPs was revealed. The cytotoxicity effect induced by the combination of the nanoconjugates was investigated in pancreatic cancer cell lines. Doxorubicin and varlitinib conjugated with PEGAuNPs revealed a combined effect to decrease the cell survival of the cancer line S2-013s, while reducing the drugs’ toxicity for the healthy pancreatic cells hTERT-HPNE. This study highlights the promising potential of PEGAuNPs for targeted delivery of therapeutic drugs into human cells, enhancing the antitumor growth-inhibition effect on cancer cells, and decreasing the toxicity against normal cells. In cancer therapy, the present approach based on PEGAuNP functionalization can be further explored to increase drug targeting efficiency and to reduce side effects.