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Developing facile, green, and efficient synthetic methodology for preparing surface‐functionalized nanogels has attracted tremendous attention in the field of polymer chemistry and biomaterials engineering. Herein, a series of "clickable" P(MAA‐PMA) nanogels with reactive alkyne groups were conveniently prepared by "one‐pot" reflux‐precipitation polymerization (RPP), their particle sizes and zeta potentials are solid content‐dependent. Using P(MAA‐PMA)‐1 nanogels as the model, the physicochemical properties including particle size, surface potential, morphology, solution stability, and pH/redox responsiveness were characterized in detail. Moreover, the pH/redox dual‐responsive drug release feature/kinetics and parameters were analyzed using Korsmeyer–Peppas model and Gallagher–Corrigan model. Then the surface of nanogels was facilely modified with various thiol‐containing functional ligands via thiol‐yne photo click reaction. As targeted drug carriers, doxorubicin (DOX)‐loaded folic acid (FA)‐functionalized nanogels (FA@Nanogels/DOX) demonstrated higher tumor cell proliferation inhibition effect in B16F10 cancer cells than that in CHO‐K1 normal cells, while the non‐FA‐functionalized counterparts (Nanogels/DOX) do not show similar effect. This work provides a versatile "one‐pot RPP‐photo Click functionalization" strategy to construct surface‐functionalized pH/redox dual responsive nanogels for efficient and targeted drug delivery. [ABSTRACT FROM AUTHOR]

A new series of cholesterol-bearing poly(methacrylate)s with pendant cationic (l-)-lysine (Chol-PHML) was synthesized via reversible addition–fragmentation chain transfer (RAFT) polymerization, followed by Boc-deprotection. Their structures were characterized by nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC). Then, the average particle sizes and zeta potentials of the Chol-PHML/pDNA polyplexes were examined using dynamic light scattering (DLS), and their plasmid DNA (pDNA)-binding ability was analyzed using agarose gel retardation assay. In vitro cytotoxicity of the polycations was determined using a cell counting kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) kits in HeLa cells. The polyplex's gene transfection effectiveness was investigated using a luciferase assay. The results revealed that the Chol-PHML series could efficiently bind/load pDNA with a high binding affinity (N/P < 3.0) and subsequently form nanoparticles with the sizes of 90–200 nm and zeta potentials of ∼+40 mV in an aqueous solution. The in vitro cytotoxicity and gene transfection efficiency considerably depended on the Chol-PHML vector's molecular weight. The optimal Chol-PHML27 exhibited a substantially higher gene transfection efficiency and lower cytotoxicity than those of the linear structural PLL (15 K–30K) and PHML26 control. This study presents a simple method for synthesizing biocompatible and controllable cationic gene vectors by introducing hydrophobic cholesterol moieties, which will function as a promising foundation for gene delivery. [ABSTRACT FROM AUTHOR]

Developing natural product-based anti-cancer drugs/agents is a promising way to overcome the serious side effects and toxicity of traditional chemotherapeutics for cancer treatment. However, rapid assessment of the in vivo anti-cancer activities of natural products is a challenge. Alternatively, zebrafish are useful model organisms and perform well in addressing this challenging issue. Nowadays, a growing number of studies have utilized zebrafish models to evaluate the in vivo activities of natural compounds. Herein, we reviewed the application of zebrafish models for evaluating the anti-cancer activity and toxicity of natural products over the past years, summarized its process and benefits, and provided future outlooks for the development of natural product-based anti-cancer drugs. [ABSTRACT FROM AUTHOR]