Glucocorticoid receptor-targeted liposomal delivery of wnt/β-catenin pathway inhibitor selectively induces efficient colorectal tumor regression.

Wnt/β-catenin signaling pathway is a highly conserved developmental pathway. This pathway is also involved in colorectal cancer and thus its selective targeting to cancer cells, albeit the risk involved, can serve as a promising therapeutic approach. Glucocorticoid receptor (GR) is a nuclear hormone receptor present in both cancer and non-cancer cells.

Targeting steroid hormone receptors for anti-cancer therapy.

Steroid Hormone Receptors (SHRs) when bound to its ligand can act as transcription factors, which are responsible for transcription of important genes via hormone responsive element in our genome. Many studies have revealed the molecular mechanisms involved with SHRs. Cancer specific aberrant expression pattern of SHR and variation in their mechanism created an opportunity to specifically target SHRs for developing highly effective anti-cancer therapeutics.

Emergence of In Vitro Glioblastoma Survival via Adaptive Quasi-Quiescence by Emulsion Copolymer Matrix.

In nature, many organisms enhance their chances of survival by adapting their structures to changing environments. Such adaptation is demonstrated herein, in glioblastoma, via spheroid assembling on the surface of engineered emulsion matrix. Glioblastoma multiforme, the most challenging primary brain malignancy, is characterized by its aggressive nature and poor patient outcomes.

Metabolic Reprogramming of Urothelial Carcinoma-A Theragnostic Target for Betulinic Acid.

A pivotal role of metabolic reprogramming in urothelial carcinoma is hallmarked by the dependence of two-fold faster proliferation of urothelial carcinoma cell line T24 than benign cell line TRT-HU1 on five-fold higher glucose (basal) 16 mM vs. 3 mM in McCoy's 5A media and Keratinocyte Serum Free media, respectively. Here, we report that an additional 10% increase to 17.

Investigation for the pro-angiogenic properties of eggshell-derived nanoparticles.

Eggshells are regular domestic, agricultural waste, and the primary composition of eggshells is majorly of calcium, as well as trace amounts of magnesium and phosphorous. These two elements (calcium and magnesium) are also present in living organisms and play an important role in many biological processes (cell growth, muscle contraction, glycolysis, angiogenesis, and vasculogenesis). Considering their role in different biological processes, especially in angiogenesis (formation of new blood vessels from pre-existing vasculature), we hypothesized the involvement of calcium and magnesium (present in eggshells) in the nanoform may induce angiogenesis.

Mixed Solvent Assisted Growth Of Eu(III) Doped Calcium Phosphate Micro/Nanoparticles for Efficient Cell Imaging Applications.

The production of biomimetic materials have become an emerging topic owing to their good biocompatible nature, which promotes better properties and improved performance in biomedicine. Herein, we prepare Eu doped calcium phosphate nanoparticles(NPs) by co-precipitation method with varied pH using a mixed solvent system of ethylene glycol and water where ethylene glycol acts as capping ligand while synthesis. The as-synthesized NPs are structurally characterized with various characterization techniques such as XRD, FTIR, TGA-DSC, FE-SEM, TEM, and so on.

Permanently Charged Cationic Lipids-Evolution from Excipients to Therapeutic Lipids.

Cationic lipids are crucial in medical and biotechnological applications including cellular transfection and gene delivery. Ionizable cationic lipids are critical components of the mRNA-based COVID vaccines while permanently charged cationic lipids have shown promise in cancer treatment. Despite significant research progress over the past few decades in designing improved, biocompatible cationic lipids, their transfection efficiency remains lower than that of viral vectors.

Glucocorticoid Receptor-Targeted Nanoliposome for STAT3 Inhibition-Led Myeloid-Derived Suppressor Cell Modulation and Efficient Colon Cancer Treatment.

STAT3 is an important protein responsible for cellular proliferation, motility, and immune tolerance and is hyperactive in colorectal cancer, instigating metastasis, cellular proliferation, migration, as well as inhibition. It helps in proliferation of myeloid-derived suppressor cells (MDSCs), which within the tumor microenvironment (TME) suppress T cells to encourage tumor growth, metastasis, and resistance to immunotherapy, besides playing dynamic role in regulating macrophages within the tumor. Thus, MDSC is a potential target to augment immune surveillance within the TME.

Gold nanoparticles-based targeted delivery of rapamycin and Olaparib to breast cancer: An in vitro and in vivo approach.

Triple negative form of breast cancer (abbreviated as TNBC) is considered as the most aggressive form causing high mortality worldwide. Different treatment modalities such as chemotherapy, surgery, hormonal therapy and radiation therapy are employed for eliminating breast cancer, which are associated with many limitations. Therefore, considering the significance of metal nanoparticles in the biomedical sector, especially gold nanoparticles, in the current manuscript, we have designed and developed a combinatorial approach for synthesizing two types of gold (Au) nanoformulations (Au-Dex-MUA-Rapa, Au-Dex-MUA-Ola) using 11-mercaptoundecanoic acid (MUA), dexamethasone (Dex) (glucocorticoid receptor targeted molecule) along with rapamycin (Rapa: inhibitor of mTOR) or olaparib (Ola: inhibitor of PARP) against TNBC.

Effective Targeting of Colorectal Cancer Stem Cells by Inducing Differentiation Mediated by Low-Dose Vitamin C via β-Catenin Retention in the Cell Membrane.

Cancer stem cells (CSCs) are implicated as the underlying cause of tumor recurrence due to their refractoriness to conventional therapies. Targeting CSCs through novel approaches can hinder their survival and proliferation, potentially reducing the challenges associated with tumor relapse. Our previous study demonstrated that colorectal cancer stem cells (CR-CSCs) showed sensitivity to Vitamin C (Vit C), displaying a dose-responsive effect where low doses (2-10 µM) promoted cell proliferation while high doses induced cell death.

Lipid-Conjugated Reduced Haloperidol in Association with Glucose-Based Nanospheres: A Strategy for Glioma Treatment.

Aggressive glioma exhibits a poor survival rate. Increased tumor aggression is linked to both tumor cells and tumor-associated macrophages (TAMs), which induce pro-aggression, invasion, and metastasis. Imperatively, for effective treatment, it is important to target both glioma cells and TAMs.

Enhancing cancer immunotherapy with mannose mimicking glycopolymer nanoparticles induced activation of Dendritic cells.

Cancer immunotherapy leverages the immune system's inherent capacity to combat malignancies. However, effective stimulation of Dendritic cells (DCs) is challenging due to their limited distribution and the immune-suppressive tumor microenvironment. Thus, targeting mannose receptors, which are highly expressed on DCs, represents a promising strategy.

Design and synthesis of a shikimoyl-functionalized cationic di-block copolypeptide for cancer cell specific gene transfection.

Targeted and efficient gene delivery systems hold tremendous potential for the improvement of cancer therapy by enabling appropriate modification of biological processes. Herein, we report the design and synthesis of a novel cationic di-block copolypeptide, incorporating homoarginine (HAG) and shikimoyl (LSA) functionalities (HDA-b-PHAGm-b-PLSAn), tailored for enhanced gene transfection specifically in cancer cells. The di-block copolypeptide was synthesized sequential -carboxyanhydride (NCA) ring-opening polymerization (ROP) techniques and its physicochemical properties were characterized, including molecular weight, dispersity, secondary conformation, size, morphology, and surface charge.

Integrin receptor-targeted, doxorubicin-loaded cerium oxide nanoparticles delivery to combat glioblastoma.

To assess the chemo-immunomodulatory effects of doxorubicin-loaded cerium oxide nanoparticles coated with oleyl amine-linked cyclic RGDfK peptide (CeNP+Dox+RGD) to target both gliomas and its tumor microenvironment (TME) via integrin receptors. CeNP+Dox+RGD nanoparticles are synthesized by the sequential addition of cerium III chloride heptahydrate, beta-cyclodextrin, oleic acid, and F127 micelle (CeNP). Doxorubicin was then loaded into CeNPs and coated with oleyl amine-linked cyclic RGDfK peptide to form stable CeNP+Dox+RGD nanoparticles.

Inhibition of the MALT1-LPCAT3 axis protects cartilage degeneration and osteoarthritis.

The proinflammatory cytokines and arachidonic acid (AA)-derived eicosanoids play a key role in cartilage degeneration in osteoarthritis (OA). The lysophosphatidylcholine acyltransferase 3 (LPCAT3) preferentially incorporates AA into the membranes. Our recent studies showed that MALT1 [mucosa-associated lymphoid tissue lymphoma translocation protein 1]) plays a crucial role in propagating inflammatory signaling triggered by IL-1β and other inflammatory mediators in endothelial cells.

Bis-arylidene oxindoles for colorectal cancer nanotherapy.

Oxindoles are potent anti-cancer agents and are also used against microbial and fungal infections and for treating neurodegenerative diseases. These oxindoles are earlier established as estrogen receptor (ER)-targeted agents for killing ER (+) cancer cells. Our previously developed bis-arylidene oxindole, Oxifen (OXF) exhibits effective targeting towards ER (+) cancer cells which has a structural resemblance with tamoxifen.

A systematic study of the effect of lipid architecture on cytotoxicity and cellular uptake of cationic cubosomes.

Hypothesis: Lipid nanoparticles containing a cationic lipid are increasingly used in drug and gene delivery as they can display improved cellular uptake, enhanced loading for anionic cargo such as siRNA and mRNA or exhibit additional functionality such as cytotoxicity against cancer cells. This research study tests the hypothesis that the molecular structure of the cationic lipid influences the structure of the lipid nanoparticle, the cellular uptake, and the resultant cytotoxicity.

Experiments: Three potentially cytotoxic cationic lipids, with systematic variations to the hydrophobic moiety, were designed and synthesised.

Steroid hormone receptor based gene delivery systems as potential oral cancer therapeutics.

Glucocorticoid and Mineralocorticoid receptors are principally ligand-dependent intracellular transcription factors that are known to influence the development and growth of many human cancers. Our study investigates the potential of these receptors to act as a target for oral cancer treatment since findings in this regard are sparse till date. Leveraging the aberrant behavior of steroid hormone receptors (SHRs) in cancer, we have targeted oral cancer cells in 2D-culture using liposomes containing both synthetic as well as crude, natural SHR ligands isolated from an aqueous Indian medicinal plant.

Glucocorticoid receptor mediated sensitization of colon cancer to photodynamic therapy induced cell death.

Photodynamic therapy (PDT) is a clinically approved, non-invasive alternate cancer therapy. A synthetic glucocorticoid (GC), dexamethasone (Dex) has previously been demonstrated to sensitize cancer cells to chemotherapy. However, to the best of our knowledge, the sensitization effect of GCs on PDT has not yet been investigated.

Delivery of chemotherapeutic drug targeting folate receptor to oral cancer cells using functionalized carbon nanospheres.

Folate receptor (FR) () has long been the subject of active interest as regards its potential to serve as a target for cancer therapy. FR has been found to be overexpressed in several cancers, including clinical samples of different stages from OSCC (oral squamous cell carcinoma) patients. However, no clear correlation or conclusive finding has been obtained so far which might indicate the efficacy of FR as a credible target for the treatment of OSCC.

Novel bioactive cationic cubosomes enhance the cytotoxic effect of paclitaxel against a paclitaxel resistant prostate cancer cell-line.

Hypothesis The study aimed to use molecular hybridization of a cationic lipid with a known pharmacophore to produce a bifunctional lipid having a cationic charge to enhance fusion with the cancer cell surface and biological activity via the pharmacophoric head group. Experiments The novel cationic lipid DMP12 [N-(2-(3-(3,4-dimethoxyphenyl) propanamido) ethyl)-N-dodecyl-N-methyldodecan-1-aminium iodide] was synthesised by conjugating 3-(3,4-dimethoxyphenyl) propanoic acid (or 3,4-dimethoxyhydrocinnamic acid) to twin 12 carbon chains bearing a quaternary ammonium group [N-(2-aminoethyl)-N-dodecyl-N-methyldodecan-1-aminium iodide]. The physicochemical and biological properties of DMP12 were investigated.

Progesterone-Cationic Lipid Conjugate-Based Self-Aggregates for Cancer Cell-Selective Uptake through Macropinocytosis and the Antitumour Effect.

Progesterone (PR) is an endogenous steroid hormone that activates the progesterone receptor (PgR) and is known to play a critical role in cancer progression. Herein, we report the development of cationic lipid-conjugated PR derivatives by covalently conjugating progesterone with cationic lipids of varying hydrocarbon chain lengths ( = 6-18) through a succinate linker. Cytotoxicity studies performed on eight different cancer cell lines reveal that PR10, one of the lead derivatives, exerts notable toxicity (IC = 4-12 μM) in cancer cells irrespective of their PgR expression status and remains largely nontoxic to noncancerous cells.

Etoposide-Entrapped Progesterone-Cationic Lipid Nanoaggregates as Selective Therapeutics against Etoposide-Resistant Colorectal Cancer Cells.

Drug resistance has a major impact on the treatment of several cancers. This is mainly due to the overexpression of cellular drug efflux proteins. Hence, drug-delivery systems that can avoid this resistance are needed.