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RNA interference (RNAi) is a unique treatment approach used to decrease a disease's excessive gene expression, including cancer. SiRNAs may find and destroy homologous mRNA sequences within the cell thanks to RNAi processes. However, difficulties such poor cellular uptake, off-target effects, and susceptibility to destruction by serum nucleases in the bloodstream restrict the therapeutic potential of siRNAs. Since some years ago, siRNA-based therapies have been in the process of being translated into the clinic. Therefore, the primary emphasis of this work is on sophisticated nanocarriers that aid in the transport of siRNA payloads, their administration in combination with anticancer medications, and their use in the treatment of cancer. The research looks into molecular manifestations, difficulties with siRNA transport, the design and development of siRNA-based delivery methods, and the benefits and drawbacks of various nanocarriers. The trapping of siRNA in endosomes is a challenge for the majority of delivery methods, which affects the therapeutic effectiveness. Numerous techniques for siRNA release, including as pH-responsive release, membrane fusion, the proton sponge effect, and photochemical disruption, have been studied to overcome this problem. The present state of siRNA treatments in clinical trials is also looked at in order to give a thorough and systematic evaluation of siRNA-based medicines for efficient cancer therapy. [ABSTRACT FROM AUTHOR]

The latest advancements in oncology involves the creation of multifunctional nanostructures. The integration of nanoparticles into the realm of cancer therapy has brought about a transformative shift, revolutionizing the approach to addressing existing challenges and limitations in tumor elimination. This is particularly crucial in combating the emergence of resistance, which has significantly undermined the effectiveness of treatments like chemotherapy and radiotherapy. GO stands as a carbon-derived nanoparticle that is increasingly finding utility across diverse domains, notably in the realm of biomedicine. The utilization of GO nanostructures holds promise in the arena of oncology, enabling precise transportation of drugs and genetic material to targeted sites. GO nanomaterials offer the opportunity to enhance the pharmacokinetic behavior and bioavailability of drugs, with documented instances of these nanocarriers elevating drug accumulation at the tumor location. The GO nanostructures encapsulate genes, shielding them from degradation and facilitating their uptake within cancer cells, thereby promoting efficient gene silencing. The capability of GO to facilitate phototherapy has led to notable advancements in reducing tumor progression. By PDT and PTT combination, GO nanomaterials hold the capacity to diminish tumorigenesis. GO nanomaterials have the potential to trigger both cellular and innate immunity, making them promising contenders for vaccine development. Additionally, types of GO nanoparticles that respond to specific stimuli have been applied in cancer eradication, as well as for the purpose of cancer detection and biomarker diagnosis. Endocytosis serves as the mechanism through which GO nanomaterials are internalized. Given these advantages, the utilization of GO nanomaterials for tumor elimination comes highly recommended. [Display omitted] • Development and introduction of nanostructures for cancer therapy can evolutionalize the treatment prospect of patients, • Graphene oxide (GO) nanoarchitectures are considered as novel platforms for targeted gene and drug delivery, • GO induce phototherapy in increasing tumor ablation and promoting response to therapy, • GO nanostructures provide immunotherapy and are beneficial for vaccine development, • GO nanoparticles can be utilized for diagnosis of cancer biomarkers and cells. [ABSTRACT FROM AUTHOR]

Breast carcinoma is a molecularly diverse illness, and it is among the most prominent and often reported malignancies in female across the globe. Surgical intervention, chemotherapy, immunotherapy, gene therapy, and endocrine treatment are among the currently viable treatment options for the carcinoma of breast. Chemotherapy is among the most prevalent cancer management strategy. Doxorubicin (DOX) widely employed as a cytostatic medication for the treatment of a variety of malignancies. Despite its widespread acceptance and excellent efficacy against an extensive line up of neoplasia, it has a variety of shortcomings that limit its therapeutic potential in the previously mentioned indications. Employment of nanoparticulate systems has come up as a unique chemo medication delivery strategy and are being considerably explored for the amelioration of breast carcinoma. Polylactic- co -glycolic acid (PLGA)-based nano systems are being utilized in a number of areas within the medical research and medication delivery constitutes one of the primary functions for PLGA given their inherent physiochemical attributes, including their aqueous solubility, biocompatibility, biodegradability, versatility in formulation, and limited toxicity. Herein along with the different application of PLGA-based nano formulations in cancer therapy, the present review intends to describe the various research investigations that have been conducted to enumerate the effectiveness of DOX-encapsulated PLGA nanoparticles (DOX-PLGA NPs) as a feasible treatment option for breast cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

Combination of gene therapy and photothermal therapy (PTT) has drawn much attention in cancer therapy in recent years. However, this joint treatment process lacks fluorescence imaging visualization guidance that limits its clinical applications in oncotherapy. Herein, we report the use of gene therapy and tungsten oxide (W 18 O 49 , WO) synthetized with template method for combined PTT of cancer. In this system, a novel nanoplatform, with Bax gene, WO and indocyanine green (ICG) loaded in mesoporous silica nanoparticle had been successfully constructed, which was used as the near-infrared imaging-guided gene/optothermal multi-modal oncotherapy. These nanoparticles could achieve a synergistic therapy effect of gene therapy and PTT for tumor under 808 nm near-infrared (NIR) laser excitation. In vivo animal experiments showed that they could cause solid tumor regression under 808 nm NIR light irradiation, revealing the potential of these nanocomposites as a fluorescence imaging-guided multi-modal therapeutic nanosystem for tumor visual synergistic treatment. [ABSTRACT FROM AUTHOR]

6-Methylpurine (MeP) is cytotoxic adenine analog that does not exhibit selectivity when administered systemically, and could be very useful in a gene therapy approach to cancer treatment involving Escherichia coli PNP. The prototype MeP releasing prodrug, 9-(β- d -ribofuranosyl)-6-methylpurine, MeP-dR has demonstrated good activity against tumors expressing E. coli PNP, but its antitumor activity is limited due to toxicity resulting from the generation of MeP from gut bacteria. Therefore, we have embarked on a medicinal chemistry program to identify non-toxic MeP prodrugs that could be used in conjunction with E. coli PNP. In this work, we report on the synthesis of 9-(6-deoxy-β- d -allofuranosyl)-6-methylpurine ( 3 ) and 9-(6-deoxy-5- C -methyl-β- d -ribo-hexofuranosyl)-6-methylpurine ( 4 ), and the evaluation of their substrate activity with several phosphorylases. The glycosyl donors; 1,2-di- O -acetyl-3,5-di- O -benzyl-α- d -allofuranose ( 10 ) and 1- O -acetyl-3- O -benzyl-2,5-di- O -benzoyl-6-deoxy-5- C -methyl-β- d -ribohexofuran-ose ( 15 ) were prepared from 1,2:5,6-di- O -isopropylidine-α- d -glucofuranose in 9 and 11 steps, respectively. Coupling of 10 and 15 with silylated 6-methylpurine under Vorbrüggen glycosylation conditions followed conventional deprotection of the hydroxyl groups furnished 5′- C -methylated-6-methylpurine nucleosides 3 and 4 , respectively. Unlike 9-(6-deoxy-α- l - talo -furanosyl)-6-methylpurine, which showed good substrate activity with E. coli PNP mutant (M64V), the β- d - allo -furanosyl derivative 3 and the 5′-di- C -methyl derivative 4 were poor substrates for all tested glycosidic bond cleavage enzymes. [ABSTRACT FROM AUTHOR]

Abstract: Delivery vectors having targeting ligands provide an impending impact on cancer gene therapy. Our work focuses on folate mediated targeting induced by conjugating poly(ethylene glycol)–folate (PEG–FA) with arginine modified chitosan polymer having low molecular weight of 15kDa and high degree of quaternization (ATFP15H). The ATFP15H derivative on condensation with plasmid DNA formed nanoparticles with core shell nanostructure. It also affirmed good buffering capacity. The derivative was found to protect DNA from DNase I degradation and also from disassembly in presence of negatively charged plasma proteins. It exhibited blood compatibility in terms of percentage hemolysis, erythrocyte aggregation and also by platelet activation. At a concentration of 10μg, the capability of the derivative to enhance cell growth at normal cell growing conditions was observed. The transfection efficiency was also found to be comparable to PEI when transfected in KB cell line, which over expressed the folate receptor (FR) in presence of 10% fetal bovine serum (FBS). On comparison with native chitosan and trimethylated chitosan, ATFP15H derivative exhibited high cellular uptake and nuclear localization due to the superior colloidal stability attained on conjugation with polyethylene glycol. This has been ascertained by flow cytometry and YOYO labeling of plasmid DNA. [Copyright &y& Elsevier]

Abstract: Adenoviral vectors are highly efficient at transferring genes into cells and are broadly used in cancer gene therapy. However, many therapeutic genes are toxic to vector host cells and thus inhibit vector production. The truncated form of E2F-1 (E2Ftr), which lacks the transactivation domain, can significantly induce cancer cell apoptosis, but is also toxic to HEK-293 cells and inhibits adenovirus replication. To overcome this, we have developed binary- and single-vector systems with a modified tetracycline-off inducible promoter to control E2Ftr expression. We compared several vectors and found that the structure of expression cassettes in vectors significantly affects E2Ftr expression. One construct expresses high levels of inducible E2Ftr and efficiently causes apoptotic cancer cell death by activation of caspase-3. The approach developed in this study may be applied in other viral vectors for encoding therapeutic genes that are toxic to their host cells and/or inhibit vector propagation. [Copyright &y& Elsevier]

Abstract: Virotherapy of cancer using oncolytic adenoviruses has shown promise in both preclinical and clinical settings. One important challenge to reach the full therapeutic potential of oncolytic adenoviruses is accomplishing efficient infection of cancer cells and avoiding uptake by normal tissue through tropism modification. Towards this goal, we constructed and characterized an oncolytic adenovirus, carrying mutated capsid proteins to abolish the promiscuous adenovirus native tropism and encoding a bispecific adapter molecule to target the virus to the epidermal growth factor receptor (EGFR). The new virus displayed a highly selective targeting profile, with reduced infection of EGFR-negative cells and efficient killing of EGFR-positive cancer cells including primary EGFR-positive osteosarcoma cells that are refractory to infection by conventional adenoviruses. Our method to modify adenovirus tropism might thus be useful to design new oncolytic adenoviruses for more effective treatment of cancer. [Copyright &y& Elsevier]

Vesicular stomatitis virus (VSV) is a candidate for development for cancer therapy. It is an oncolytic virus that is safe in humans. Recombinant virus can be made directly from plasmid components. We attempted to create a virus that targeted specifically to breast cancer cells. Nonreplicating and replicating pseudotype VSV were created whose only surface glycoprotein (gp) was a Sindbis gp, called Sindbis-ZZ, modified to severely reduce its native binding function and to contain the Fc-binding domain of Staphylococcus aureus protein A. When titered on Her2/neu overexpressing SKBR3 human breast cancer cells, pseudotype VSV coated with Sindbis-ZZ had <1% the titer of pseudotype VSV coated with wild-type Sindbis gp. Titer was increased 50-fold when the Sindbis-ZZ pseudotype was conjugated with 4D5, a mouse monoclonal antibody directed against the Her2/neu receptor. Titers of antibody-conjugated virus were increased 36-fold on a second human breast cancer cell line, MCF7/H2, which expressed lower concentrations of Her2/neu receptor on the cell surface. At multiple concentrations of antibody, titers on SKBR3 cells were significantly greater when the virus was incubated with Herceptin, an antibody with a human Fc, than with 4D5, a mouse antibody, reflecting the known higher affinity of the protein A Fc-binding domain for human Fc. Analysis of the protein composition of the pseudotype VSV found low expression of the modified Sindbis gp on the virus accounting, in part, for a viral titer that did not exceed 1.2 × 105/ml. This work demonstrates the ability to easily create, directly from plasmid components, an oncolytic replicating VSV with a restricted host cell range. [Copyright &y& Elsevier]