2D and 3D Covalent Organic Frameworks: Cutting-Edge Applications in Biomedical Sciences.

Covalent organic frameworks (COFs) are crystalline porous organic structures with two- or three-dimensional (2D or 3D) features and composed of building blocks being connected via covalent bonds. The manifold applications of COFs in optoelectronic devices, energy conversion and storage, adsorption, separation, sensing, organocatalysis, photocatalysis, electrocatalytic reactions, and biomedicine are increasing because of their notable intrinsic features such as large surface area, porosity, designable structure, low density, crystallinity, biocompatibility, and high chemical stability. These properties have rendered 2D and 3D COF-based materials as desirable entities for drug delivery, gene delivery, photothermal therapy, photodynamic therapy, combination therapy, biosensing, bioimaging, and anticancer activities. Herein, different reactions and methods for the synthesis of 2D and 3D COFs are reviewed with special emphasis on the construction and state-of-the-art progress pertaining to the biomedical applications of 2D and 3D COFs of varying shapes, sizes, and structures. Specifically, stimuli-responsive COFs-based systems and targeted drug delivery approaches are summarized.

Miktoarm Star Polymers with Environment-Selective ROS/GSH Responsive Locations: From Modular Synthesis to Tuned Drug Release through Micellar Partial Corona Shedding and/or Core Disassembly.

Branched architectures with asymmetric polymeric arms provide an advantageous platform for the construction of tailored nanocarriers for therapeutic interventions. Simple and adaptable synthetic methodologies to amphiphilic miktoarm star polymers have been developed in which spatial location of reactive oxygen species (ROS) and glutathione (GSH) responsive entities is articulated to be on the corona shell surface or inside the core. The design of such architectures is facilitated through versatile building blocks and selected combinations of ring-opening polymerization, Steglich esterification, and alkyne-azide click reactions. Soft nanoparticles from aqueous self-assembly of these stimuli responsive miktoarm stars have low critical micelle concentrations and high drug loading efficiencies. Partial corona shedding upon response to ROS is accompanied by an increase in drug release, without significant changes to overall micelle morphology. The location of the GSH responsive unit at the core leads to micelle disassembly and complete drug release. Curcumin loaded soft nanoparticles show higher efficiencies in preventing ROS generation in extracellular and cellular environments, and in ROS scavenging in human glioblastoma cells. The ease in synthetic elaboration and an understanding of structure-property relationships in stimuli responsive nanoparticles offer a facile venue for well-controlled drug delivery, based on the extra- and intracellular concentrations of ROS and GSH.

Telodendrimer-Based Macromolecular Drug Design using 1,3-Dipolar Cycloaddition for Applications in Biology.

An architectural polymer containing hydrophobic isoxazole-based dendron and hydrophilic polyethylene glycol linear tail is prepared by a combination of the robust ZnCl2 catalyzed alkyne-nitrile oxide 1,3-dipolar cycloaddition and esterification chemistry. This water soluble amphiphilic telodendrimer acts as a macromolecular biologically active agent and shows concentration dependent reduction of glioblastoma (U251) cell survival.

Bounded Fuzzy Possibilistic Method Reveals Information about Lung Cancer through Analysis of Metabolomics.

Learning methods, such as conventional clustering and classification, have been applied in diagnosing diseases to categorize samples based on their features. Going beyond clustering samples, membership degrees represent to what degree each sample belongs to a cluster. Variation of membership degrees in each cluster provides information about the cluster as a whole and each sample individually which enables us to have insights toward precision medicine. Membership degrees are measured more accurately through removing restrictions from clustering samples. Bounded Fuzzy Possibilistic Method (BFPM) introduces a membership function that keeps the search space flexible to cluster samples with higher accuracy. The method evaluates samples for their movement from one cluster to another. This technique allows us to find critical samples in advance those with the potential ability to belong to other clusters in the near future. BFPM was applied on metabolomics of individuals in a lung cancer case-control study. Metabolomics as proximal molecular signals to the actual disease processes may serve as strong biomarkers of current disease process. The goal is to know whether serum metabolites of a healthy human can be differentiated from those with lung cancer. Using BFPM, some differences were observed, the pathology data were evaluated, and critical samples were recognized.

Stimuli-responsive chitosan as an advantageous platform for efficient delivery of bioactive agents.

Despite a diverse range of active pharmaceutical agents currently at our disposal, high morbidity rate diseases continue to pose a major health crisis globally. One of the important parameters in this regard is the controlled cargo delivery at desired sites. Among a variety of synthetic and natural macromolecular systems, chitosan, an abundant biopolymer, offers a platform for tailored architectures that could have high loading capacity of cargo, target and deliver. Stimuli directed accumulation of vehicles and drug release is an area of direct relevance to biomedical applications. In this review, we highlight essential characteristics of modified chitosan that present themselves for efficient response through an internal (glutathione, reactive oxygen species, pH, temperature, enzymes, and chemical/electrical potential gradient), and external stimuli (ultrasound, light, mechanical stimuli, magnetic and electrical fields). With a brief review of the pertinent properties of chitosan that are relevant to biology, the design and critical evaluation of varied chitosan-based platforms is discussed. Future directions in exploiting important features of chitosan in this area can be derived from the presented comparative evaluation of the current literature in drug delivery.