Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer.

Breast cancer, the most frequent female malignancy, is often curable when detected at an early stage. The treatment of metastatic breast cancer is more challenging and may be unresponsive to conventional therapy. Immunotherapy is crucial for treating metastatic breast cancer, but its resistance is a major limitation. The tumor microenvironment (TME) is vital in modulating the immunotherapy response. Various tumor microenvironmental components, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs), are involved in TME modulation to cause immunotherapy resistance. This review highlights the role of stromal cells in modulating the breast tumor microenvironment, including the involvement of CAF-TAM interaction, alteration of tumor metabolism leading to immunotherapy failure, and other latest strategies, including high throughput genomic screening, single-cell and spatial omics techniques for identifying tumor immune genes regulating immunotherapy response. This review emphasizes the therapeutic approach to overcome breast cancer immune resistance through CAF reprogramming, modulation of TAM polarization, tumor metabolism, and genomic alterations.

Therapeutic implications of cancer stem cells in prostate cancer.

Prostate cancer, one of the most frequently occurring cancers in men, is a heterogeneous disease involving multiple cell types within tumors. This tumor heterogeneity at least partly results from genomic instability leading to sub-clonal cellular differentiation. The differentiated cell populations originate from a small subset of cells with tumor-initiating and stem-like properties. These cells, termed prostate cancer stem cells (PCSCs), play crucial roles in disease progression, drug resistance, and relapse. This review discusses the origin, hierarchy, and plasticity of PCSCs; methods for isolation and enrichment of PCSCs; and various cellular and metabolic signaling pathways involved in PCSC induction and maintenance, as well as therapeutic targeting.

Gelatin interpenetration in poly N-isopropylacrylamide network reduces the compressive modulus of the scaffold: A property employed to mimic hepatic matrix stiffness.

The progression of liver disease from normal to cirrhotic state is characterized by modulation of the stiffness of the extracellular matrix (ECM). Mimicking this modulation in vitro scaffold could provide a better insight into hepatic cell behavior. In this study, interpenetrating poly(N-isopropylacrylamide-co-gelatin) cryogels were synthesized in 48 different compositions to yield scaffolds of different properties. It was observed that a high concentration of N-isopropylacrylamide (NIPAAm) leads to the formation of small pores while gelatin interpenetration on poly-NIPAAm framework renders porous structure. Swelling properties and porosity of the gels decreased with an increase in NIPAAm concentration owing to the increased compactness of the gels. Gelatin interpenetration relaxed the gels and enhanced these properties. An increase in gelatin concentration led to a reduction in compressive moduli indicating that gelatin interpenetration in the poly-NIPAAm network softens the cryogel. With the increase in NIPAAm concentration, the effect of gelatin interpenetration in reducing the compressive moduli expanded. The cytocompatibility studies indicated that the gels are cell-adherent and compatible with HepG2. Furthermore, biochemical and real-time polymerase chain reaction studies revealed that HepG2 and Huh-7 cells cultured on scaffolds mimicking the ECM stiffness of normal liver (1.5-2.5 kPa) exhibited optimum liver-specific functionalities. Increasing the stiffness to fibrotic (4-9 kPa) and cirrhotic (10-20 kPa) ECM decreases the functionality.

Functional design of pH-responsive folate-targeted polymer-coated gold nanoparticles for drug delivery and in vivo therapy in breast cancer.

BACKGROUND: Curcumin has been widely used owing to its various medicinal properties including antitumor effects. However, its clinical application is limited by its instability, poor solubility and low bioavailability. Folic acid (FA)-functionalized nanoformulations may enhance the sustained release of an anticancer drug (curcumin) by tumor-specific targeting to improve therapeutic benefit. This study aims to design a nanoconjugate (NC) comprised of folate-curcumin-loaded gold-polyvinylpyrrolidone nanoparticles (FA-CurAu-PVP NPs) for targeted delivery in breast cancer model systems. METHODS: We developed curcumin-loaded FA-functionalized Au-PVP NCs by layer-by-layer assembly. The folic acid-curcumin Au-PVP NCs (FA-CurAu-PVP NCs) were characterized by ultraviolet-visible spectra, Fourier transform infrared spectroscopy, X-ray powder diffraction and thermogravimetric analysis. In vitro anticancer and antimigratory effects of NCs were examined by performing MTT and wound migration assays. The in vivo antitumor efficacy of NCs was investigated using a preclinical breast cancer orthotopic mouse model. RESULTS: Curcumin (40 µg/mL) was loaded along with conjugation of folate onto Au-PVP NPs to form FA-CurAu-PVP NCs. The size and charge of the NCs were increased gradually through layer-by-layer assembly and showed 80% release of curcumin at acidic pH. The NC did not show aggregation when incubated with human serum and mimicked an intrinsic peroxidase-like property in the presence of 3,3',5,5'-tetramethylbenzidine substrate. The MTT data using these NCs showed efficient anticancer activity at lower doses in estrogen/progesterone receptor (ER/PR)-negative cells compared with ER/PR-positive cells. Furthermore, the NCs did not show cytotoxicity at the investigated concentration in human breast epithelial and mouse fibroblast cell lines. They showed inhibitory effects on cell migration and high antitumor efficacy in in vivo analysis. CONCLUSION: These results suggest that folate-based tumor targeting using CurAu-PVP NCs is a promising approach for tumor-specific therapy of breast cancer without harming normal cells.

Helminthicidal and Larvicidal Potentials of Biogenic Silver Nanoparticles Synthesized from Medicinal Plant Momordica charantia.

BACKGROUND: The drug formulations used to control mosquito vectors and helminth infections have resulted in the development of resistance, and negative impact on non-target organisms and environment. OBJECTIVE: Plant-mediated synthesis of silver nanoparticles (P-AgNPs) using aqueous fruit peel extract of M. charantia, applications of P-AgNPs for helminthicidal activity against Indian earthworms (P. posthuma) and larvicidal activity against larvae of mosquito A. albopictus and A. aegypti. METHODS: Aqueous fruit peel extract of Momordica charantia was used to reduce silver ions to silver nanoparticles (P-AgNPs). UV-Visible (UV-Vis) Spectroscopy, X-ray diffraction, Fourier Transform Infrared Spectroscopy and Transmission Electron Microscopy characterize synthesized P-AgNPs. The motility and survival rate of the worms were recorded for the helminthicidal activity. Percent mortality of larvae of A. albopictus and A. aegypti was recorded for larvicidal activity. RESULTS: The UV-Vis absorption spectrum of P-AgNPs showed a strong surface plasmon absorption band in the visible region with a maximum absorption at 445 nm indicating the synthesis of silver nanoparticles by the addition of aqueous fruit peel extract. The XRD spectrum of P-AgNPs showed Bragg's reflection peaks 2θ value characteristics for the Face-Centered Cubic (FCC) structure of silver. The sharp absorption peak in FTIR at 1659 cm-1 assigned to C=O stretching vibration in carbonyl compounds represents terpenoids, flavonoids and polyphenols in the corona of PAgNPs; a 2 mg/mL of P-AgNPs. The concentration aqueous extract and P-AgNPs showed complete death of worms (the morphological alteration/coiling of body). A 20 ppm concentration of PAgNPs showed 85% mortality in larvae of Ae. albopictus and Ae. aegypti. P-AgNPs were nontoxic at low concentrations. CONCLUSION: The aqueous extracts played a dual role as reducing and capping agent during the biosynthesis of AgNPs as per FTIR and XRD results. The surface reactivity facilitated by biomolecule corona attached to silver nanoparticles can further help to functionalize AgNPs in various pharmaceuticals, biomedicals, and environmental applications.

Bioinspired inimitable cadmium telluride quantum dots for bioimaging purposes.

Synthesis of quantum nanoparticles of specific size, shape and composition are an aspect important in nanotechnology research. Although these nanostructures are routinely synthesized by chemical routes, the use of microorganisms has emerged as a promising option. The synthesis of cadmium telluride (CdTe) quantum dots by two hitherto unreported marine bacteria (Bacillus pumilus and Serratia marcescens) is reported here. Ultraviolet-visible (UV-vis) spectroscopy indicated the synthesis of CdTe nanoparticles and X-ray diffraction (XRD) patterns implicated their crystalline face-centered cubic nature. The size of the synthesized CdTe nanostructures estimated by XRD and dynamic light scattering (DLS) analysis was found to be approximately 10 nm. Photoluminescence (PL) studies were used to confirm the fluorescence properties of these semi-conducting nanoparticles. Scanning electron microscope (SEM) analysis showed the presence of well-defined nanostructures and energy dispersive spectra (EDS) confirmed the microbial synthesis of these nanoparticles. These bio-inspired CdTe nanostructures could be effectively used in imaging of yeast and animal cells. This work thus describes a cost-effective green method for synthesizing highly fluorescent biocompatible CdTe nanoparticles suitable for bio-labeling purposes.

Antimicrobial activity of silica coated silicon nano-tubes (SCSNT) and silica coated silicon nano-particles (SCSNP) synthesized by gas phase condensation.

Silica-coated, silicon nanotubes (SCSNTs) and silica-coated, silicon nanoparticles (SCSNPs) have been synthesized by catalyst-free single-step gas phase condensation using the arc plasma process. Transmission electron microscopy and scanning tunneling microscopy showed that SCSNTs exhibited a wall thickness of less than 1 nm, with an average diameter of 14 nm and a length of several 100 nm. Both nano-structures had a high specific surface area. The present study has demonstrated cheaper, resistance-free and effective antibacterial activity in silica-coated silicon nano-structures, each for two Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration (MIC) was estimated, using the optical densitometric technique, and by determining colony-forming units. The MIC was found to range in the order of micrograms, which is comparable to the reported MIC of metal oxides for these bacteria. SCSNTs were found to be more effective in limiting the growth of multidrug-resistant Staphylococcus aureus over SCSNPs at 10 µg/ml (IC 50 = 100 µg/ml).

Sulfite reductase-mediated synthesis of gold nanoparticles capped with phytochelatin.

An enzymatic synthesis route to peptide-capped gold nanoparticles has been developed. Gold nanoparticles were synthesized using alpha-NADPH-dependent sulfite reductase and phytochelatin in vitro. The gold ions were reduced in the presence of the enzyme sulfite reductase, leading to the formation of a stable gold hydrosol of dimensions 7-20 nm and were stabilized by the capping peptide. The nanoparticles were characterized by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy and UV-visible optical absorption. These studies will help in designing a rational enzymatic strategy for the synthesis of nanomaterials of different chemical compositions, shapes and sizes as well as their separation.