Clinical Advances in Triple Negative Breast Cancer Treatment: Focus on Poly (L-lactide-coglycolide) Nanoparticles.

Triple negative breast cancer (TNBC) is the most aggressive type of breast cancer and is associated with high probability of metastasis and poor prognosis. Chemotherapeutics and surgery remain the most common options for TNBC patients; however, chemotherapeutic resistance and relapse of tumors limit the progression free survival and patient life span. This review provides an overview of recent chemotherapeutics that are in clinical trial, and the combination of drugs that are being investigated to overcome the drug resistance and to improve patient survival in different molecular subtypes of TNBCs. Nanotherapeutics have emerged as a promising platform for TNBC treatment and aim to improve the selectivity and solubility of drugs, reduce systemic side effects, and overcome multi-drug resistance. The study explores the role of nanoparticles for TNBC treatment and summarizes the types of nanoparticles that are in clinical trials. Poly(L-lactide-co-glycolide) (PLGA) is the most studied polymeric carrier for drug delivery and for TNBC treatment in research and in clinics. This review is about providing recent advancements in PLGA nanotherapeutic formulations and their application to help treat TNBC. Some background on current chemotherapies and pathway inhibitors is provided so that the readers are aware of what is currently considered for TNBC. Some of the pathway inhibitors may also be of importance for nanotherapeutics development. SIGNIFICANCE STATEMENT: This minireview summarizes the progress on chemotherapeutics and nanoparticle delivery for treatment of TNBC and specifically highlights the lead compounds that are in clinical trials.

Metastatic Breast Cancer: Review of Emerging Nanotherapeutics.

Metastases of breast cancer (BC) are often referred to as stage IV breast cancer due to their severity and high rate of mortality. The median survival time of patients with metastatic BC is reduced to 3 years. Currently, the treatment regimens for metastatic BC are similar to the primary cancer therapeutics and are limited to conventional chemotherapy, immunotherapy, radiotherapy, and surgery. However, metastatic BC shows organ-specific complex tumor cell heterogeneity, plasticity, and a distinct tumor microenvironment, leading to therapeutic failure. This issue can be successfully addressed by combining current cancer therapies with nanotechnology. The applications of nanotherapeutics for both primary and metastatic BC treatments are developing rapidly, and new ideas and technologies are being discovered. Several recent reviews covered the advancement of nanotherapeutics for primary BC, while also discussing certain aspects of treatments for metastatic BC. This review provides comprehensive details on the recent advancement and future prospects of nanotherapeutics designed for metastatic BC treatment, in the context of the pathological state of the disease. Furthermore, possible combinations of current treatment with nanotechnology are discussed, and their potential for future transitions in clinical settings is explored.

Enhanced Cryopreservation Efficacies of Ice Recrystallization Inhibiting Nanogels.

Development of new cryopreservation technologies holds significant potential to revolutionize the fields of cell culture, tissue engineering, assisted reproduction, and transfusion medicine. The current gold standard small-cell permeating cryopreservation agents (CPAs) demonstrate promising cryopreservation efficacies but are cytotoxic and immunogenic at the concentrations required for cryopreservation applications. In comparison, new cell impermeable CPAs of nanodimensions demonstrate outstanding potential to overcome the drawbacks of existing CPAs. In this study, we report the synthesis of vitamin B5 analogous methacrylamide (B5AMA)-incorporated nanogels as a potential solution to address the commonly observed limitations of existing CPAs. The stimuli-responsive poly(B5AMA) nanogels prepared by radical polymerization demonstrated significant ice recrystallization inhibition efficacies and showed either superior or comparable cryopreservation efficacies compared to the traditional cryoprotectant DMSO/glycerol in both eukaryotic and prokaryotic cells.

Antimicrobial and Alpha-Amylase Inhibitory Activities of Organic Extracts of Selected Sri Lankan Bryophytes.

Medicinal plants have been the main focus of natural product research. However, recent research has revealed that lower plants including bryophytes are also a major resource of biologically active compounds with novel structures. Sri Lanka is considered as a biodiversity hotspot with a higher degree of endemism flora including bryophytes. In this study, different species of bryophytes were investigated for their antimicrobial and alpha-amylase inhibitory activities. The air-dried plant materials of 6 different bryophyte species, Marchantia sp., Fissidens sp., Plagiochila sp., Sematophyllum demissum, Hypnum cupressiforme, and Calymperes motley, were subjected to sequential cold extraction with 3 different organic solvents. All three types of organic crude extracts were subjected to screening of antimicrobial bioassays using the disc-diffusion method against 3 bacterial strains and 1 fungal strain. According to the results obtained, 6 extracts out of 18 showed antibacterial activity for tested Gram-positive bacteria and 1 active against Gram-negative bacteria. Two extracts showed activity against the pathogenic fungus strain. Extracts from some plants were active against tested bacterial as well as fungal species. TLC-based bioautographic study was carried out to identify the corresponding active bands which is useful for active compound isolation. Furthermore, the ethyl acetate extracts were subjected to evaluate alpha-amylase inhibitory activity where three extracts out of six extracts showed moderate inhibitory activity for alpha-amylase with IC50 ranging 8-30%.

Curcumin loaded zinc oxide nanoparticles for activity-enhanced antibacterial and anticancer applications.

Zinc oxide nanoparticles and curcumin have been shown to be excellent antimicrobial agents and promising anticancer agents, both on their own as well as in combination. Together, they have potential as alternatives/supplements to antibiotics and traditional anticancer drugs. In this study, different morphologies of zinc oxide-grafted curcumin nanocomposites (ZNP-Cs) were synthesized and characterized using SEM, TGA, FTIR, XRD and UV-vis spectrophotometry. Antimicrobial assays were conducted against both Gram negative and Gram-positive bacterial stains. Spherical ZnO-curcumin nanoparticles (SZNP-Cs) and rod-shaped ZnO-curcumin nanoparticles showed the most promising activity against tested bacterial strains. The inhibition zones for these curcumin-loaded ZnO nanocomposites were consistently larger than their bare counterparts or pure curcumin, revealing an additve effect between the ZnO and curcumin components. The potential anticancer activity of the synthesized nanocomposites was studied on the rhabdomyosarcoma RD cell line via MTT assay, while their cytotoxic effects were tested against human embryonic kidney cells using the resazurin assay. SZNP-Cs exhibited the best balance between the two, showing the lowest toxicity against healthy cells and good anticancer activity. The results of this investigation demonstrate that the nanomatrix synthesized can act as an effective, additively-enhanced combination delivery/therapeutic agent, holding promise for anticancer therapy and other biomedical applications.

Drug-Loaded Halloysite Nanotube-Reinforced Electrospun Alginate-Based Nanofibrous Scaffolds with Sustained Antimicrobial Protection.

Halloysite nanotube (HNT)-reinforced alginate-based nanofibrous scaffolds were successfully fabricated by electrospinning to mimic the natural extracellular matrix (ECM) structure which is beneficial for tissue regeneration. An antiseptic drug, cephalexin (CEF)-loaded HNT, was incorporated into the alginate-based matrix to obtain sustained antimicrobial protection and robust mechanical properties, the key criteria for tissue engineering applications. Electron microscopic imaging and drug release studies revealed that CEF had penetrated into the lumen space of the HNT and also deposited on the outer walls, with a total loading capacity of 30 wt %. Moreover, the diameter of alginate-based nanofibers of the scaffolds ranged from 40 to 522 nm with well-aligned HNTs, resulting in superior mechanical properties. For instance, the addition of 5% (w/w) HNT improved the tensile strength (σ) and elastic modulus by 3-fold and 2-fold, respectively, compared to those of the alginate-based scaffolds without HNT. The fabricated scaffolds exhibited remarkable antimicrobial properties against both Gram-negative and Gram-positive bacteria, and the cytotoxicity studies confirmed the nontoxicity of the fabricated scaffolds. Drug release kinetics showed that CEF inside HNTs diffuses within 24 h and that the diffusion of the drug is delayed by 7 days once the CEF-loaded HNTs are incorporated into the alginate-based nanofibers. These fabricated alginate-based electrospun scaffolds with enhanced mechanical properties and sustained antimicrobial protection hold great potential to be used as artificial ECM scaffolds for tissue engineering applications.

Antimicrobial activities of endophytic fungi of the Sri Lankan aquatic plant Nymphaea nouchali and chaetoglobosin A and C, produced by the endophytic fungus Chaetomium globosum.

Twenty distinct endophytic fungi were isolated from the surface-sterilized plant parts of Nymphaea nouchali and were identified using morphological and molecular techniques. At 300 µg/disc concentration, eight of the 20 fungal extracts exhibited antimicrobial activities against Staphylococcus aureus (ATCC 25923) and Bacillus cereus (ATCC 11778) while two within the eight showed activity against Pseudomonas aeruginosa (ATCC 9027) and Escherichia coli (ATCC 35218). Furthermore, investigation of the crude extract of Chaetomium globosum resulted in the isolation of two known cytochalasans, chaetoglobosin A and C, and their structures were elucidated and confirmed by mass and nuclear magnetic resonance (NMR) (1H, 13C, COSY, HSQC, HMBC and tROESY) spectral data. Chaetoglobosin A showed antibacterial activities against Bacillus subtilis (MIC 16 µg mL-1), Staphylococcus aureus (MIC 32 µg mL-1) and methicillin-resistant Staphylococcus aureus (MRSA, MIC 32 µg mL-1). This is the first study to report the isolation, identification and antimicrobial properties of endophytic fungi of N. nouchali in Sri Lanka.

Antimicrobial activities of mycoleptodiscin B isolated from endophytic fungus Mycoleptodiscus sp. of Calamus thwaitesii Becc.

Endophytic fungi are a promising source of novel biologically active compounds including antimicrobials. Plant endophytic fungi of Sri Lanka, an island with exceptionally high biodiversity and endemism, are a vastly untapped resource. Therefore this study was initiated with the objective of examining the antimicrobial producing potential of the endophytic fungi of Calamus thwaitesii Becc. from Sri Lanka. This examination resulted in the isolation of 21 fungi with 7 of them exhibiting antimicrobial properties. Further investigation of the Mycoleptodiscus sp. isolated from the leaves, which showed the best activity among them, resulted in the isolation of the known alkaloid mycoleptodiscin B and its structure was elucidated and confirmed by mass and nuclear magnetic resonance spectral data. Mycoleptodiscin B showed promising antimicrobial activity against Bacillus subtilis (MIC 0.5 µg mL-1) and Staphylococcus aureus (MIC 1 µg mL-1), and was less potent against methicillin resistant Staphylococcus aureus (MRSA, MIC 32 µg mL-1) and the pathogenic fungus Candida albicans (MIC 64 µg mL-1). This is the first study to report the isolation, identification and antimicrobial properties of endophytic fungi of C. thwaitesii and the antimicrobial activities of the alkaloid mycoleptodiscin B.