Design and development of in-vitro co-culture device for studying cellular crosstalk in varied tissue microenvironment.

Despite of being in different microenvironment, breast cancer cells influence the bone cells and persuade cancer metastasis from breast to bone. Multiple co-culture approaches have been explored to study paracrine signaling between these cells and to study the progression of cancer. However, lack of native tissue microenvironment remains a major bottleneck in existing co-culture technologies. Therefore, in the present study, a tumorigenic and an osteogenic microenvironment have been sutured together to create a multi-cellular environment and has been appraised to study cancer progression in bone tissue. The PCL-polystyrene and PCL-collagen fibrous scaffolds were characterized for tumorigenic and osteogenic potential induction on MDA-MB-231 and MC3T3-E1 cells respectively. Diffusion ability of crystal violet, glucose, and bovine serum albumin across the membrane were used to access the potential paracrine interaction facilitated by device. While in co-cultured condition, MDA-MB-231 cells showed EMT phenotype along with secretion of TNFα and PTHrP which lower down the expression of osteogenic markers including alkaline phosphatase, RUNX2, Osteocalcin and Osteoprotegerin. The cancer progression in bone microenvironment demonstrated the role and necessity of creating multiple tissue microenvironment and its contribution in studying multicellular disease progression and therapeutics.

Site-selective post-modification of short α/γ hybrid foldamers: a powerful approach for molecular diversification towards biomedical applications.

The extensive research work in the exhilarating area of foldamers (artificial oligomers possessing well-defined conformation in solution) has shown them to be promising candidates in biomedical research and materials science. The post-modification approach is successful in peptides, proteins, and polymers to modulate their functions. To the best of our knowledge, site-selective post-modification of a foldamer affording molecules with different pendant functional groups within a molecular scaffold has not yet been reported. We demonstrate for the first time that late-stage site-selective functionalization of short hybrid oligomers is an efficient approach to afford molecules with diverse functional groups. In this article, we report the design and synthesis of hybrid peptides with repeating units of leucine (Leu) and 5-amino salicylic acid (ASA), regioselective post-modification, conformational analyses (based on solution-state NMR, circular dichroism and computational studies) and morphological studies of the peptide nanostructures. As a proof-of-concept, we demonstrate the applications of differently modified peptides as drug delivery agents, imaging probes, and anticancer agents. The novel feature of the work is that the difference in reactivity of two phenolic OH groups in short biomimetic peptides was utilized to achieve site-selective post-modification. It is challenging to apply the same approach to short α-peptides having a poor folding tendency, and their post-functionalization may considerably affect their conformation.

Differential Migration and Proliferation Potential of the Hydrogel Aided 3D Tumoroid.

For substantial in vitro cancer biology research, the 3D cell culture method has now been regarded as more suitable model expected to be recapitulating maximum in vivo tumor mass relevance. Despite of available techniques to develop in vitro 3D models, a system availing a physiologically relevant in vitro 3D model of primary lung adenocarcinoma with extracellular matrix (ECM) mimicry and similar tumorigenic properties still remains a quest. Thus, in the present study, chemically modified Dextran-Chitosan (MDC) hydrogel has been developed as a 3D tumoroid aiding scaffold. The 3D A549 tumoroids aided by the MDC scaffold have physiologically relevant proliferation, migration, invasive potential, and Gefitinib [targeting epidermal growth factor receptor (EGFR)] efficacy as compared to the 2D cultured cells. The surface topography and wettability of hydrogel availed in vivo micro tumor mass mimicking Lung adenocarcinoma 3D in vitro model. Thus, opening an innovative avenue for elucidating the disease mechanism and drug efficacy on relevant 3D cancer models in vitro.

Molecular insights of metastasis and cancer progression derived using 3D cancer spheroid co-culture in vitro platform.

The multistep metastasis process is carried out by the combinatorial effect of the stromal cells and the cancerous cells and plays vital role in the cancer progression. The scaffold/physical cues aided 3D cancer spheroid imitates the spatiotemporal organization and physiological properties of the tumor. Understanding the role of the key players in different stages of metastasis, the molecular cross-talk between the stromal cells and the cancer cells contributing in the advancement of the metastasis through 3D cancer spheroid co-culture in vitro platform is the center of discussion in the present review. This state-of-art in vitro platform utilized to study the cancer cell host defence and the role of exosomes in the cross talk leading to cancer progression has been critically examined here. 3D cancer spheroid co-culture technique is the promising next-generation in vitro approach for exploring potent treatments and personalized medicines to combat cancer metastasis leading to cancer progression.