Cutting-edge approaches for targeted drug delivery in breast cancer: beyond conventional therapies.

Breast cancer is a global health challenge with staggering statistics underscoring its pervasive impact. The burden of this disease is measured in terms of its prevalence and the challenges it poses to healthcare systems, necessitating a closer look at its epidemiology and impact. Current breast cancer treatments, including surgery, chemotherapy, radiation therapy, and targeted therapies, have made significant strides in improving patient outcomes. However, they are not without limitations, often leading to adverse effects and the development of drug resistance. This comprehensive review delves into the complex landscape of breast cancer, including its incidence, current treatment modalities, and the inherent limitations of existing therapeutic approaches. It also sheds light on the promising role of nanotechnology, encompassing both inorganic and organic nanoparticles equipped with the ability to selectively deliver therapeutic agents to tumor sites, in the battle against breast cancer. The review also addresses the emerging therapies, their associated challenges, and the future prospects of targeted drug delivery in breast cancer management.

Reprogramming M1-to-M2 Phenotype to Alleviate Inflammation: Using Liposomal Curcumin as a Tool to Redefine Macrophage Functionality.

The versatile nature of macrophages and their ability to switch between various activation states plays a pivotal role in both promoting and inhibiting inflammatory processes. In pathological inflammatory conditions, classically activated M1 macrophages are often associated with initiating and maintaining inflammation, while alternatively activated M2 macrophages are linked to the resolution of chronic inflammation. Achieving a favorable equilibrium between M1 and M2 macrophages is crucial for mitigating inflammatory environments in pathological conditions. Polyphenols are known to have strong inherent antioxidative capabilities, and curcumin has been found to reduce macrophage inflammatory reactions. However, its therapeutic efficacy is compromised due to its poor bioavailability. The present study aims to harness the properties of curcumin by loading it in nanoliposomes and enhancing the M1-to-M2 macrophage polarization. A stable liposome formulation was achieved at 122.1 ± 0.08 nm, and a sustained kinetic release of curcumin was observed within 24 h. The nanoliposomes were further characterized using TEM, FTIR, and XRD, and the morphological changes in macrophage cells, RAW264.7, were observed in SEM, indicating a distinct M2-type phenotype after the treatment with liposomal curcumin. ROS may partially control macrophage polarization and be observed to decrease after treatment with liposomal curcumin. The nanoliposomes were able to successfully internalize in the macrophage cells, and an enhanced expression of ARG-1 and CD206 with a decrease in iNOS, CD80, and CD86 levels suggested the polarization of LPS-activated macrophages toward the M2 phenotype. Also, liposomal curcumin treatment dose-dependently inhibited TNF-α, IL-2, IFN-γ, and IL-17A at secretory levels and simultaneously increased the levels of cytokines like IL-4, IL-6, and IL-10.

Fabrication, assessment, and potential anti-bacterial activity of sandalwood oil nanoemulsion and its hand rub sanitizer.

In the last decade, extensive research has been performed on developing hand sanitizers that can be used to eradicate the diseases that are caused due to poor hand hygiene. Essential oils possess antibacterial and antifungal properties and thus have great potential to replace the available antibacterial agents. In the present study, sandalwood oil-based nanoemulsion (NE) and sanitizer have been formulated and well characterized for their properties. Antibacterial activity was assessed using growth inhibition studies, agar cup, viability assay, etc. The sandalwood oil NE synthesized had oil to surfactant ratio of 1:0.5 (2.5% sandalwood oil and 0.5% Tween 80) and was observed to have a droplet diameter of 118.3 ± 0.92 nm, the zeta potential of - 18.8 ± 2.01 mV, and stability of 2 months. The antibacterial activity of sandalwood NE and sanitizer was evaluated against microorganisms. The antibacterial activity was assessed using the zone of inhibition value of sanitizer, which was in the range of 19 to 25 mm against all microorganisms. Morphological analysis showed distant changes in membrane shape and size and microorganisms' morphology. The synthesized NE was thermodynamically stable and efficient enough to be used in sanitizer, and the formulated sanitizer showed great antibacterial efficacy.

Development of food-grade antimicrobials of fenugreek oil nanoemulsion-bioactivity and toxicity analysis.

Antimicrobials of natural origin are proving to be an effective solution to emerging antimicrobial resistance and its physiological side effects. Recent studies have demonstrated that essential oils encapsulated in the form of nanoemulsions have better antimicrobial activity than the oil itself, possibly due to its high stability, solubility, sustained release, and increased bioavailability. In the present study, fenugreek oil-a well-known antimicrobial and antioxidant-has been used to fabricate nanoemulsion (NE), with an objective to meet potential alternative to synthesized antimicrobials. A combination of three different components, water, fenugreek oil, and Tween 80, has been used to prepare the nanoemulsions of different size and one of the most stable nanoemulsion with lowest concentration of surfactant Tween 80 was used to assess its bioactivity, antimicrobial properties, and toxicity against human hepatic cell line. Among all the formulations, nano-emulsion with 2.5% oil concentration, 30 min sonication (hydrodynamic size 135.2 nm, zeta potential 36.8 mV, PDI 0.135, and pH 5.12), was selected for all studies. The nanoemulsion showed potential antibacterial activity against all the microbial strains (Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa) used in this study. Interestingly, the nanoemulsion showed potential antibacterial activity against P. aeruginosa, known to show resistance against ampicillin. The toxicity evaluation in human hepatic cell line (WRL-68) indicated no significant toxicity of nanoemulsion up to the concentration of 800 µg/ml. The synthesized nanoemulsion thus has a translational potential as a food-grade non-toxic natural nanoantimicrobials.

MiR-206 conjugated gold nanoparticle based targeted therapy in breast cancer cells.

MicroRNAs (miRNAs) are single-stranded, non-coding, 19-25 nucleotide RNA molecules that have been observed to be dysregulated in many diseases including cancer. miRNAs have been known to play an important role in cellular proliferation, differentiation, migration, apoptosis, survival, and morphogenesis. Breast cancer is heterogeneous in nature and contributed extensively to the increased mortality rate. miRNA can either be tumor-suppressive or oncogenic in nature. The level of expression of miRNA changes according to the subtypes of cancer and the mutation responsible for different cancers. miRNA mimicry or inhibition are emerging possible therapies to maintain the level of miRNA inside the cells. In order to have proper miRNA mimicry, the major hurdle is to deliver the miRNA mimics at the site of tumor. Metallic nanoparticles with modified surface can be used to solve the problem of miRNA delivery. MiR-206 is reported to be down-regulated in Luminal-A type of breast cancer. In the current manuscript, we aim to modify the surface of gold-nanoparticles (AuNPs) with PEG moiety and allow miRNA to attach to it. The fabricated nano-complex, not only delivered miR-206 but also caused cell death in MCF-7 by arresting cells in the G0-G1 phase and inducing apoptosis by downregulating NOTCH 3.

Fabrication of methotrexate-loaded gold nanoconjugates and its enhanced anticancer activity in breast cancer.

Methotrexate (MTX) is known antagonist of folic acid and widely used as an anti-cancer drug. The folate receptor (FR) and reduced folate carrier are mostly responsible for internalization of methotrexate in tumor cells. Mutation in reduced folate carrier (RFC) leads to resistance against MTX in various tumor cell lines including MDA-MB-231 breast cancer cells. To overcome the resistance of MTX, folate receptor targeted nanoparticles have been commonly used for targeting breast tumors. The aim of the study is to determine the ability of methotrexate gold nanoparticles (MTX-GNPs) in the induction of apoptosis and to explore the molecular changes at genomics and proteomics level. Different assays like cell viability assay, cell cycle analysis, apoptosis, real-time PCR and western blot were carried out to evaluate the anti-cancer effect of MTX-Gold NPs on MCF-7 and MDA-MB-231 cells. Our observations demonstrated the decrease in the percent viable cells after the treatment of MTX-GNPs, with an arrest in cell cycle at G0/G1 phase and a significant increase in apoptotic cell population and loss of mitochondrial membrane potential in MCF-7 and MDA-MB-231 cells. Folate receptor targeted MTX-GNPs showed significant cellular uptake in breast cancer cells along with significant down-regulation in expression of anti-apoptotic gene (Bcl-2) and up-regulation in expression of pro-apoptotic genes (Bax, Caspase-3, Caspase-9, APAF-1, p53). These results unveil the increased anti-cancer effect of MTX-GNPs in cancer cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02718-7.

Transdermal Immunization of Elastic Liposome-Laden Recombinant Chimeric Fusion Protein of P. falciparum (PfMSP-Fu24) Mounts Protective Immune Response.

Transdermal immunization exhibits poor immunogenic responses due to poor permeability of antigens through the skin. Elastic liposomes, the ultradeformable nanoscale lipid vesicles, overcome the permeability issues and prove a versatile nanocarrier for transcutaneous delivery of protein, peptide, and nucleic acid antigens. Elastic liposome-mediated subcutaneous delivery of chimeric fusion protein (PfMSP-Fu24) of Plasmodium falciparum exhibited improved immunogenic responses. Elastic liposomes-mediated immunization of PfMSP-Fu24 conferred immunity to the asexual blood-stage infection. Present study is an attempt to compare the protective immune response mounted by the PfMSP-Fu24 upon administered through transdermal and intramuscular routes. Humoral and cell-mediated immune (CMI) response elicited by topical and intramuscularly administered PfMSP-Fu24-laden elastic liposomes (EL-PfMSP-Fu24) were compared and normalized with the vehicle control. Sizeable immune responses were seen with the transcutaneously immunized EL-PfMSP-Fu24 and compared with those elicited with intramuscularly administered antigen. Our results show significant IgG isotype subclass (IgG1and IgG3) response of specific antibody levels as well as cell-mediated immunity (CMI) activating factor (IFN-γ), a crucial player in conferring resistance to blood-stage malaria in mice receiving EL-PfMSP-Fu24 through transdermal route as compared to the intramuscularly administered formulation. Heightened immune response obtained by the vaccination of EL-PfMSP-Fu24 was complemented by the quantification of the transcript (mRNA) levels cell-mediated (IFN-γ, IL-4), and regulatory immune response (IL-10) in the lymph nodes and spleen. Collectively, elastic liposomes prove their immune-adjuvant property as they evoke sizeable and perdurable immune response against PfMSP-Fu24 and justify its potential for the improved vaccine delivery to inducing both humoral and CM immune response.

Genetic diversity of 15 autosomal short tandem repeats loci using the AmpFLSTR(®) Identifiler™ kit in a Bhil Tribe Population from Gujarat state, India.

MATERIALS AND METHODS: The genetic diversity and forensic parameters based on 15 autosomal short tandem repeats (STR) loci; D8S1179,D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317,D16S539, D2S1338, D19S433, vWA, TPOX, D18S51,D5S818, and FGA in AmpFLSTR® Identifiler™ kit from Applied Biosystems, Foster City, CA, USA were evaluated in saliva samples of 297 unrelated individuals from the Bhil Tribe population of Gujarat state, India to study genetic diversities and relatedness of this population with other national and international populations. RESULTS: Statistical analysis of the data revealed all loci were within Hardy-Weinberg Equilibrium expectations with the exception of the locus vWA (0.019) and locus D18S51 (0.016). The neighbour joining phylogeny tree and Principal Co-ordinate Analysis plot constructed based on Fst distances from autosomal STRs allele frequencies of the present study and other national as well as international populations show clustering of all the South Asian populations in one branch of the tree, while Middle Eastern and African populations cluster in a separate branch. CONCLUSION: Our findings reveal strong genetic affinities seen between the Indo-European (IE) speaking Bhil Tribe of Gujarat and Dravidian groups of South India.