Stabilizing noncovalently encapsulated guest molecules inside a nanoassembly constructed from amphiphilic polymers has become a very challenging effort in the area of targeted drug delivery of biomedical applications. The unwanted...

Dynamic covalent poly(disulfide)-based cross-linked nanoaggregates, termed nanonetworks (NNs), endowed with pH- and redox-responsive degradation features have been fabricated for stable noncovalent encapsulation and triggered cargo release in a controlled fashion. A bioderived lipoic acid-based Gemini surfactant-like amphiphilic molecule was synthesized for the preparation of nanoaggregates. It self-assembles by a entropy-driven self-assembly process in aqueous milieu. To further stabilize the self-assembled nanostructure, the core was cross-linked by ring-opening disulfide exchange polymerization (RODEP) of 1,2-dithiolane rings situated inside the core of the nanoaggregates. The cross-linked nanoaggregates, i.e., nanonetwork, are found to be stable in the presence of blood serum, and also, they maintain the self-assembled structure even below the critical aggregation concentration (CAC) as probed by dynamic light scattering (DLS) experiments. The nanonetwork showed almost 50% reduction in guest leakage compared to that of the nanoaggregates as shown by the release profile in the absence of stimuli, suggesting high encapsulation stability as evidenced by the fluorescence resonance energy transfer (FRET) experiment. The decross-linking of the nanonetwork occurs in response to redox and pH stimuli due to disulfide reduction and β-thioester hydrolysis, respectively, thus empowering disassembly-mediated controlled cargo release up to ∼87% for 55 h of incubation. The biological evaluation of the doxorubicin (DOX)-loaded nanonetwork revealed environment-specific surface charge modulation-mediated cancer cell-selective cellular uptake and cytotoxicity. The benign nature of the nanonetwork toward normal cells makes the system very promising in targeted drug delivery applications. Thus, the ease of synthesis, nanonetwork fabrication reproducibility, robust stability, triggered drug release in a controlled fashion, and cell-selective cytotoxicity behavior, we believe, will make the system a potential candidate in the development of robust materials for chemotherapeutic applications.

The role of solvents in the control over supramolecular interactions has been studied for decades in protein folding, soft material fabrication and long-range organization of functional organic π chromophores. Nonpolar...

The monomer 3 is commercially available. Monomer 1 and 2 were synthesized in laboratory and is outlined below.Monomer 1 (M1): 4,4'-Dihydroxyazobenzene (0.5 g, 2.33 mmol) and 3-bromo-1-propanol (1.94 g, 14 mmol) were taken in around bottomed flask along with activated potassium carbonate (1.93 g, 14 mmol) and catalytic amount of potassium iodide. All reactants were dissolved in 10 mL dry DMF and the reaction mixture was placed in preheated oil bath 60°C and stirred for 24 hours. Then the reaction was stopped and the reaction mixture was diluted with 20 mL Ethylacetate and washed with water for 3 times. The organic layer was collected and dried over anh. Na 2 SO 4 and evaporated to get the crude product as yellow solid in 72% yield.