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Activated Ras as a Therapeutic Target: Constraints on Directly Targeting Ras Isoforms and Wild-Type versus Mutated Proteins.

The ability to selectively and directly target activated Ras would provide immense utility for treatment of the numerous cancers that are driven by oncogenic Ras mutations. Patients with disorders driven by overactivated wild-type Ras proteins, such as type 1 neurofibromatosis, might also benefit from progress made in that context. Activated Ras is an extremely challenging direct drug target due to the inherent difficulties in disrupting the protein:protein interactions that underlie its activation and function. Major investments have been made to target Ras through indirect routes. Inhibition

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… A polylysine stretch of amino acids in the hypervariable region of this isoform confers additional targeting and association for its membrane localization [ 65 ]. …

Advances in antisense oligonucleotide development for target identification, validation, and as novel therapeutics.

Antisense oligonucleotides (As-ODNs) are single stranded, synthetically prepared strands of deoxynucleotide sequences, usually 18-21 nucleotides in length, complementary to the mRNA sequence of the target gene. As-ODNs are able to selectively bind cognate mRNA sequences by sequence-specific hybridization. This results in cleavage or disablement of the mRNA and, thus, inhibits the expression of the target gene. The specificity of the As approach is based on the probability that, in the human genome, any sequence longer than a minimal number of nucleotides (nt), 13 for RNA and 17 for DNA, normal

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… Folic acid-polylysine carrier improves efficacy of c-myc antisense oligodeoxynucleotides on human melanoma (M14) cells. Anticancer Res. 1997;17(1A):29–35. 31. Bielinska A, et al. …

Prospects and Challenges of Lung Cancer Vaccines.

Lung cancer remains one of the most prevalent and lethal malignancies worldwide. Although conventional treatments such as surgery, chemotherapy, and radiotherapy have modestly improved patient survival, their overall efficacy remains limited, and the prognosis is generally poor. In recent years, immunotherapy, particularly immune checkpoint inhibitors, has revolutionized cancer treatment. Nevertheless, the immunosuppressive tumor microenvironment, tumor heterogeneity, and immune escape mechanisms significantly restrict the clinical benefit, which falls short of expectations. Within this contex

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… preferentially expressed antigen in melanoma, CLDN6: claudin 6, KK-LC-1: Kita-Kyushu lung cancer antigen-1, Pd-1: programmed cell death protein 1, ICIs: immune checkpoint inhibitors, CD8+ TIL: cluster of differentiation 8 tumor-infiltrating lymphocytes, Poly-ICLC: polyinosinic-polycytidylic acid stabilized with polylysine …

Triple-Negative Breast Cancer: Basic Biology and Immuno-Oncolytic Viruses.

Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. TNBC diagnoses account for approximately one-fifth of all breast cancer cases globally. The lack of receptors for estrogen, progesterone, and human epidermal growth factor 2 (HER-2, CD340) results in a lack of available molecular-based therapeutics. This increases the difficulty of treatment and leaves more traditional as well as toxic therapies as the only available standards of care in many cases. Recurrence is an additional serious problem, contributing substantially to its higher mortality rate as compared to

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… The proof of concept for genetic engineering in viruses had been accomplished in the 1960s via the insertion of nucleotides to express polylysine in the tobacco mosaic virus [ 112 ]. …

Novel insight and perspectives of nanoparticle-mediated gene delivery and immune-modulating therapies for pancreatic cancer.

Current standard-of-care therapies have failed to improve the survival of patients with metastatic pancreatic cancer (PCA). Therefore, exploring novel therapeutic approaches for cancer targeting is of utmost need. During the past few years, many efforts have been made to develop conventional treatment strategies to reduce chemotherapy resistance. However, critical challenges have impeded current cancer management outcomes, and limited clinical responses have been achieved due to unfavorable off-target effects. Advances in nanotechnology-based gene and immune-modulator delivery systems have exc

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… Cationic Ɛ-polylysine copolymers (ENPs) absorb surface-negatively charged si-HIF-1α efficiently and enclose Gem within the hydrophilic core. Covering the ENPs with a polyethylene glycol lipid bilayer forms reverse surface charge LENPs. …

An Overview of Polymeric Nanoparticles-Based Drug Delivery System in Cancer Treatment.

Cancer is recognized as one of the world's deadliest diseases, with more than 10 million new cases each year. Over the past 2 decades, several studies have been performed on cancer to pursue solutions for effective treatment. One of the vital benefits of utilizing nanoparticles (NPs) in cancer treatment is their high adaptability for modification and amalgamation of different physicochemical properties to boost their anti-cancer activity. Various nanomaterials have been designed as nanocarriers attributing nontoxic and biocompatible drug delivery systems with improved bioactivity. The present

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… Various dendrimers are usually prepared by divergent and convergent methods, such as poly (propylene-imine), polylysine (PLL), silicon, and phosphorus-based dendrimers. …

Уникальные диагностические и терапевтические функции порфиринов и фтальокянинов в области фотодинамической терапии, визуализации и термостимы.

Порфиринические молекулы играют уникальную тераностическую роль в лечении болезней; они используются для отображения, обнаружения и лечения различных форм заболевших тканей, в том числе в связи с возрастной маркулярной дегенерацией и рядом различных видов рака. В настоящее время основное внимание уделяется клинической съемке опухолей; целенаправленной доставке фотосенитеров и потенциалу фотоэнцедентов в мультимодальных биомедицинских наноплатформах. В настоящем Обзоре подчеркиваются роли порфириновых молекул в области съемки и пдта, а также исследования по совершенствованию их селективного пог

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… The group went on to report the conjugation of a chlorin photosensitiser (C e 6) onto a polylysine backbone 279 . … In the presence of tumour-associated enzymes (for example cathepsins), the peptide linkages of the polylysine backbone were cleaved and the “degraded” probes became highly phototoxic and fluorescent. …

Recent Advances in Cancer Vaccines: Challenges, Achievements, and Futuristic Prospects.

Cancer is a chronic disease, and it can be lethal due to limited therapeutic options. The conventional treatment options for cancer have numerous challenges, such as a low blood circulation time as well as poor solubility of anticancer drugs. Therapeutic cancer vaccines emerged to try to improve anticancer drugs' efficiency and to deliver them to the target site. Cancer vaccines are considered a viable therapeutic technique for most solid tumors. Vaccines boost antitumor immunity by delivering tumor antigens, nucleic acids, entire cells, and peptides. Cancer vaccines are designed to induce lon

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… TLR agonists that are used the most frequently include polyinosinic–polycytidylic acid with polylysine, carboxymethylcellulose, monophosphoryl lipid A, flagellin, imiquimod, and CPG-ODN [ 3 , 82 , 83 , 84 , 85 , 86 ]. 5. …

Hydrogels-Assisted Cell Engraftment for Repairing the Stroke-Damaged Brain: Chimera or Reality.

The use of advanced biomaterials as a structural and functional support for stem cells-based therapeutic implants has boosted the development of tissue engineering applications in multiple clinical fields. In relation to neurological disorders, we are still far from the clinical reality of restoring normal brain function in neurodegenerative diseases and cerebrovascular disorders. Hydrogel polymers show unique mechanical stiffness properties in the range of living soft tissues such as nervous tissue. Furthermore, the use of these polymers drastically enhances the engraftment of stem cells as w

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… To improve cell neural attachment and survival, HA hydrogels can be chemically modified with polylysine and RGD peptides [ 225 ]. In general, natural hydrogel polymers such as HA are more susceptible to suffer in vivo degradation via enzymes from the host tissue. …

Recent advances in the bench-to-bedside translation of cancer nanomedicines.

Cancer remains a complex and challenging medical problem, driving extensive research efforts. Despite significant progress in understanding its genetic and molecular aspects, the quest for effective treatments continues. Nanomedicines have shown great potential for revolutionizing cancer treatment by offering targeted and controlled drug delivery, reducing side effects, and improving patient outcomes. Accordingly, nanomedicines have been the focus of extensive research and development for clinical translation. As of September 2024, a search on the ClinicalTrials.gov website using the term "nan

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… This assay, incorporating a nanolayer of polylysine on the microfluidic chip, effectively detected T-cell responses in vaccinated or previously infected individuals. The nanolayer enhanced cell capture, allowing for sensitive, rapid, and cost-effective, high-throughput analysis. …

Trials and Tribulations of MicroRNA Therapeutics.

The discovery of the link between microRNAs (miRNAs) and a myriad of human diseases, particularly various cancer types, has generated significant interest in exploring their potential as a novel class of drugs. This has led to substantial investments in interdisciplinary research fields such as biology, chemistry, and medical science for the development of miRNA-based therapies. Furthermore, the recent global success of SARS-CoV-2 mRNA vaccines against the COVID-19 pandemic has further revitalized interest in RNA-based immunotherapies, including miRNA-based approaches to cancer treatment. Cons

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… Furthermore, diazobenzene, azobenzene, and estradiol have been shown to inhibit the transcription of the miR-21 [ 204 , 205 ], while, polylysine has been shown to inhibit the maturation process of pre-miR-21 by inhibiting Dicer [ 201 ]. …

The potential therapeutic role of extracellular vesicles in critical-size bone defects: Spring of cell-free regenerative medicine is coming.

In recent years, the incidence of critical-size bone defects has significantly increased. Critical-size bone defects seriously affect patients' motor functions and quality of life and increase the need for additional clinical treatments. Bone tissue engineering (BTE) has made great progress in repairing critical-size bone defects. As one of the main components of bone tissue engineering, stem cell-based therapy is considered a potential effective strategy to regenerate bone tissues. However, there are some disadvantages including phenotypic changes, immune rejection, potential tumorigenicity,

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… Meanwhile, the adsorption of EVs on the scaffold material was enhanced by coating the scaffold surface with positively charged polylysine to mediate charge interaction. …

Engineering precision nanoparticles for drug delivery.

In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers - systemic, microenvironmental and cellular - that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-

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… Charged materials currently used for nucleic acid delivery include lipids (lipofectamine, rationally designed lipids, combinatorial libraries of ionizable lipid-like materials) 21 , 22 , 274 and polymers (polyethylene imine (PEI), jetPEI, poly(amido amine) (PAA), polylysine (PLL), cyclodextrins and poly …

MicroRNA-7: a versatile player and core target in brain disorders.

OBJECTIVE: This article provides a systematic review of the biological characteristics, regulatory mechanisms, and roles of MicroRNA-7 (miR-7) in the nervous system, as well as explores its clinical translation potential and challenges. METHODS: A review analysis integrating the progress of basic and clinical research related to miR-7. RESULTS: Characteristics and Regulation: miR-7 is highly expressed in mammalian brain tissues, with its function finely regulated by ceRNA networks (such as ciRS-7 and lncRNA SNHG1) and epigenetic modifications, forming a multi-layer dynamic regulatory system.

The Evolving Landscape of Immune Regulation and Immunotherapy in Cholangiocarcinoma and Biliary Tract Cancer.

Cholangiocarcinoma (CCA) is an aggressive and molecularly heterogeneous malignancy characterized by a profoundly immunosuppressive tumor microenvironment (TME) and historically limited therapeutic options. Recent advances have redefined the treatment paradigm, with phase III trials establishing chemoimmunotherapy as a standard of care and multi-omic profiling elucidating the interplay between tumor genomics, stromal architecture, and immune regulation. Despite these gains, durable clinical benefit remains confined to a minority of patients, reflecting convergent mechanisms of primary and acqui

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… Abbreviations: BTC, biliary tract cancer; CCA, cholangiocarcinoma; DC, dendritic cell; GC, gemcitabine/cisplatin; poly-ICLC, polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose . …

Emerging insights into the immunosuppressive tumor microenvironment and its implications for glioblastoma immunotherapy.

Glioblastoma is considered the most common and lethal form of brain cancer. Despite tremendous progress in glioblastoma therapeutics, the profound intra- and inter-tumoral heterogeneity of glioblastoma tumors, the difficulty of agents to cross the blood-brain barrier (BBB), the development of drug resistance as well as the immunosuppressive tumor microenvironment (TME) predominantly account for the failure of existing conventional and targeted therapies. Therefore, there is a growing necessity to decipher the complexity of the TME that promotes immunosuppression and to discover innovative stra

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… It has several features including: (1) a survivin promoter for enhancing specific replication in tumor cells, since survivin is found to be overexpressed in glioblastoma, (2) a modified Ad5 protein through insertion of polylysine sequence (pk7), which binds to heparin sulfate proteoglycans also overexpressed …

Transformative Impact of Nanocarrier-Mediated Drug Delivery: Overcoming Biological Barriers and Expanding Therapeutic Horizons.

Advancing therapeutic progress is centered on developing drug delivery systems (DDS) that control therapeutic molecule release, ensuring precise targeting and optimal concentrations. Targeted DDS enhances treatment efficacy and minimizes off-target effects, but struggles with drug degradation. Over the last three decades, nanopharmaceuticals have evolved from laboratory concepts into clinical products, highlighting the profound impact of nanotechnology in medicine. Despite advancements, the effective delivery of therapeutics remains challenging because of biological barriers. Nanocarriers offe

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… Various dendrimeric formulations have been employed as nanodrugs for treating diverse diseases, including antiviral formulations containing polylysine dendrimers with sulfonated naphthyl groups, antibacterial agents comprising PPL dendrimers with tertiary alkylammonium groups, and chitosan dendrimer …

The progress and perspective of nanomedicine in modulating the tumor immune microenvironment.

The widespread application of nanomedicine in oncology is reshaping cancer treatment paradigms. Using the precise targeting mechanisms and the rapid advancements in nanoscale materials, nanomedicine is driving progress in cancer therapy, particularly within the complex landscape of the tumor immune microenvironment (TIM). This review provides a comprehensive overview of recent studies elucidating the critical role of nanomedicine in modulating the TIM, augmenting the efficacy of immunotherapies, and overcoming therapeutic resistance. Emphasis is placed on the significance of targeted drug deli

Musculoskeletal Organs-on-Chips: An Emerging Platform for Studying the Nanotechnology-Biology Interface.

Nanotechnology-based approaches are promising for the treatment of musculoskeletal (MSK) disorders, which present significant clinical burdens and challenges, but their clinical translation requires a deep understanding of the complex interplay between nanotechnology and MSK biology. Organ-on-a-chip (OoC) systems have emerged as an innovative and versatile microphysiological platform to replicate the dynamics of tissue microenvironment for studying nanotechnology-biology interactions. This review first covers recent advances and applications of MSK OoCs and their ability to mimic the biophysic

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… progenitor cells; SM = systemic mastocytosis; RUNX2 = Runt‐related transcription factor 2; SAMD = mothers against decapapentaplegic; BGN = bioactive glass nanoparticles; BMSCs = bone marrow mesenchymal stem cells; NFATc1 = nuclear factor of activated T cells 1; UPR = unfolded protein response; PPD = ɛ‐polylysine–polyethylene–distearyl …

Abstracts from the 8th Drug Hypersensitivity Meeting (DHM)

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