Protein/Polymer‐Based Dual‐Responsive Gold Nanoparticles with pH‐Dependent Thermal Sensitivity

This article presents the synthesis and physicochemical behavior of dual‐responsive plasmonic nanoparticles with reversible optical properties based on protein‐coated gold nanoparticles grafted with thermosensitive polymer brushes by means of surface‐initiated atom transfer radical polymerization (SI‐ATRP) that exhibit pH‐dependent thermo‐responsive behavior. Spherical gold NPs of two different sizes (15 nm and 60 nm) and with different stabilizing agents (citrate and cetyltrimethylammonium bromide (CTAB), respectively) were first capped with bovine serum albumin (BSA). The resulting BSA‐capped NPs (Au@BSA NPs) exhibited not only extremely high colloidal stability under physiological conditions, but also a reversible U‐shaped pH‐responsive behavior, similar to pure BSA. The ?‐amine of the L‐lysine in the protein coating was then used to covalently bind an ATRP‐initiator, allowing for the SI‐ATRP of thermosensitive polymer brushes of oligo(ethylene glycol) methacrylates with an LCST of 42 °C in pure water and around 37 °C under physiological conditions. Such protein coated nanoparticles grafted with thermosensitive polymers exhibit a smart pH‐dependent thermosensitive behavior.     

Lipid‐Containing Polymer Vesicles with pH/Ca2+‐Ion‐Manipulated,Size‐Selective Permeability

Polymeric vesicles attained from the self‐assembly of distearin (a diacylglycerol lipid)‐conjugated poly(acrylic acid) (PAAc) with various distearin contents in the aqueous phase show the capability of control over the vesicular‐wall permeability to hydrophilic solutes of varying sizes by a simple manipulation of the external pH. The pH sensitivity of the vesicle membranes in size‐selective permeability is largely dependent upon the lipid content of copolymer. By the addition of CaCl₂ in aqueous vesicle suspensions, the pH‐evolved assembly structure and the membrane permeability can be immobilized with promoted resistance to further pH alteration, along with an additional counterion screening effect that reduces the pH required for the onset of polar solutes of certain sizes to pass through the membranes. Small‐angle X‐ray scattering (SAXS) measurements of the vesicle structure in the aqueous phase indicate that the pH‐regulated permeability to polar solutes is virtually governed by the extent of hydration and swelling of the vesicle membranes, and the lipid residues within each vesicle wall are packed into the ≈4–5 repeating lamellar islet structure surrounded by PAAc segments.     

Responsive Macroscopic Materials From Self‐Assembled Cross‐Linked SiO2‐PNIPAAm Core/Shell Structures

A way to obtain macroscopic responsive materials from silicon‐oxide polymer core/shell microstructures is presented. The microparticles are composed of a 60 nm SiO₂‐core with a random copolymer corona of the temperature responsive poly‐N‐isopropylacrylamide (PNIPAAm) and the UV‐cross‐linkable 2‐(dimethyl maleinimido)‐N‐ethyl‐acrylamide. The particles shrink upon heating and form a stable gel in both water and tetrahydrofuran (THF) at 3–5 wt% particle content. Cross‐linking the aqueous gel results in shrinkage when the temperature is increased above the lower critical solution temperature and it regains its original size upon cooling. By freeze drying with subsequent UV irradiation, thin stable layers are prepared. Stable fibers are produced by extruding a THF gel into water and subsequent UV irradiation, harnessing the cononsolvency effect of PNIPAAm in water/THF mixtures. The temperature responsiveness translates to the macroscopic materials as both films and fibers show the same collapsing behavior as the microcore/shell particle. The collapse and re‐swelling of the materials is related to the expelling and re‐uptake of water, which is used to incorporate gold nanoparticles into the materials by a simple heating/cooling cycle. This allows for future applications, as various functional particles (antibacterial, fluorescence, catalysis, etc.) can easily be incorporated in these systems.     

Design of Hybrid MnO2‐Polymer‐Lipid Nanoparticles with Tunable Oxygen Generation Rates and Tumor Accumulation for Cancer Treatment

Manganese dioxide (MnO₂) nanoparticles (NPs) were discovered in previous work to be effective in improving tumor oxygenation (hypoxia) and reducing H₂O₂ and acidity in the tumor microenvironment (TME) via local injection. To develop MnO₂ formulations useful for clinical application, hybrid NPs are designed with tailored hydrophobicity and structure suitable for intravenous injection, with good blood circulation, biocompatibility, high tumor accumulation, and programmable oxygen generation rate. Two different hybrid NPs are constructed by embedding polyelectrolyte‐MnO₂ (PMD) in hydrophilic terpolymer/protein‐MnO₂ (TMD) or hydrophobic polymer/lipid‐MnO₂ (LMD) matrices. The in vitro reactivity of the MnO₂ toward H₂O₂ is controlled by matrix material and NP structure and dependent on pH with up to two‐fold higher O₂ generation rate at acidic (tumor) pH than at systemic pH. The hybrid NPs are found to be safe to cells in vitro and organs in vivo and effectively decrease tumor hypoxia and hypoxia‐inducible‐factor‐1alpha through local or systemic administration. Fast acting TMD reduces tumor hypoxia by 70% in 0.5 h by local injection. Slow acting LMD exhibits superior tumor accumulation and retention through the systemic administration and decreased hypoxia by 45%. These findings encourage a broader use of hybrid MD NPs to overcome TME factors for cancer treatment.     

Chain Extension of Stimuli‐Responsive Polymer Brushes: A General Strategy to Overcome the Drawbacks of the “Grafting‐To” Approach

Stimuli‐responsive polymer brushes are smart materials for the design of bio‐interactive and responsive interfaces. The “grafting‐to” approach is a convenient preparation procedure that allows the modification of surfaces with preformed and most notably well‐defined functionalized macromolecules. However, the shortcoming of this approach is an intrinsic limitation of the grafting density, which in turn affects the stimuli‐responsive properties of the brush system. Here, a general strategy to overcome this limitation and to simultaneously improve the switching behavior of a temperature‐responsive poly(N‐isopropylacrylamide) (PNiPAAm) brush is reported. A technically simple processing step is used in combination with the thermal azide–alkyne cycloaddition to perform the chain extension of alkyne‐functionalized PNiPAAm brushes with azide‐functionalized PNiPAAm molecules.     

A Low‐Toxic Multifunctional Nanoplatform Based on Cu9S5@mSiO2 Core‐Shell Nanocomposites: Combining Photothermal‐ and Chemotherapies with Infrared Thermal Imaging for Cancer Treatment

Copper chalcogenides have been demonstrated to be a promising photothermal agent due to their high photothermal conversion efficiency, synthetic simplicity, and low cost. However, the hydrophobic and less biocompatible characteristics associated with their synthetic processes hamper widely biological applications. An alternative strategy for improving hydrophilicity and biocompatibility is to coat the copper chalcogenide nanomaterials with silica shell. Herein, the rational preparation design results in successful coating mesoporous silica (mSiO₂) on as‐synthesized Cu₉S₅ nanocrystals, forming Cu₉S₅@mSiO₂‐PEG core‐shell nanostructures. As‐prepared Cu₉S₅@mSiO₂‐PEG core‐shell nanostructures show low cytotoxicity and excellent blood compatibility, and are effectively employed for photothermal ablation of cancer cells and infrared thermal imaging. Moreover, anticancer drug of doxorubicin (DOX)‐loaded Cu₉S₅@mSiO₂‐PEG core‐shell nanostructures show pH sensitive release profile and are therefore beneficial to delivery of DOX into cancer cells for chemotherapy. Importantly, the combination of photothermal‐ and chemotherapies demonstrates better effects of therapy on cancer treatment than individual therapy approaches in vitro and in vivo.     

Luminescent Core/Shell Nanoparticles with a Rhabdophane LnPO4‐xH2O Structure: Stabilization of Ce3+‐Doped Compositions

The core/shell strategy has been successfully developed for rhabdophane lanthanide phosphate aqueous colloids. The growth of a LaPO₄‐xH₂O shell around Ce,Tb‐doped core nanoparticles increases their stability against oxidation. A bright green luminescence is thus preserved in sol–gel films whose fabrication requires silica coating and thermal treatment of the core/shell nanoparticles.