Copolymer Nanoparticles Research Articles

Solid-state solvatochromism of oxazolidine in multi-functionalized copolymer nanoparticles: Development of advanced materials with multi-color fluorescence

Solid-state solvatochromism of oxazolidine in multi-functionalized copolymer nanoparticles: Development of advanced materials with multi-color fluorescence

Synergistic Therapy of Melanoma by Co-Delivery of Dacarbazine and Ferroptosis-Inducing Ursolic Acid Using Biomimetic Nanoparticles.

Melanoma is one of the most aggressive types of cancer and is prone to metastasis, making current clinical treatment quite difficult. The usage of the first-line medication dacarbazine (DTIC) for melanoma is limited due to harsh side effects, limited water solubility, and a short half-life. To tackle these disadvantages, polylactic acid-hydroxyacetic acid copolymer nanoparticles (NPs) loaded with dacarbazine and ursolic acid (NPs) were fabricated, which were further encapsulated with a red blood cell membrane (RNPs). MTT, apoptosis assay, wound healing assay, colony formation assay, and immunohistochemistry were used to assess the antitumor effect of NPs and RNPs. Ferroptosis evaluation was implemented using GSH detection and the malondialdehyde assay. We found that RNPs exhibited stability and biosafety in vitro and in vivo and achieved superior anticancer ability against xenograft tumors compared with single agents and NPs, which indicated the synergistic and biomimetic efficacy. Furthermore, ferroptotic activity was observed in RNPs-treated tumor cells, and ferroptosis inhibition could partially rescue melanoma cells from RNPs-induced cell death. Collectively, this study evaluated the potential of RNPs as a novel biomimetic nanomedicine for synergistic melanoma therapy by eliciting ferroptosis in tumor cells with both anticancer activity and biosafety.

Probing the inner structure and dynamics of pH-sensitive block copolymer nanoparticles with nitroxide radicals using scattering and EPR techniques

This research emphasizes the crucial role of electron paramagnetic resonance (EPR) spectroscopy in nanoparticle analysis, showcasing its distinctive ability to probe molecular-level details. We demonstrate the synthesis and self-assembly of a new class of pH-responsive amphiphilic diblock copolymers, specifically poly[N-(2-hydroxypropyl)-methacrylamide]-block-poly[2-(diisopropylamino)ethyl methacrylate] (PHPMA-b-PDPA), incorporating 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radicals covalently bound to the hydrophilic PHPMA segment. The copolymer synthesis involved a three-step process, combining reversible addition − fragmentation chain transfer (RAFT) polymerization with carbodiimide (DCC) chemistry. TEMPO radical-containing nanoparticles (RNPs) were created using microfluidic (MF) nanoprecipitation, a technique essential for generating uniform nanoparticles with predictable biodistribution and cellular uptake. Adjusting MF protocol parameters allowed fine-tuning of RNP sizes. EPR spectroscopy confirmed the formation of core–shell RNPs, with features aligning closely with those obtained from scattering techniques like dynamic light scattering (DLS), static light scattering (SLS), small-angle X-ray scattering (SAXS), and cryo-transmission electron microscopy (cryo-TEM). EPR spectroscopy emerges as a potent tool for molecular-level analysis of colloidal polymer systems. This study highlights the EPR-spin label method’s efficacy in probing the internal structural features and dynamics of core–shell nanoparticles, especially their response to pH-triggered disassembly. The findings open new avenues for the use of pH-responsive TEMPO-labeled diblock copolymers in controlled drug delivery applications.

Preparation and biological evaluation of a glucose-responsive block copolymer nanoparticle with the ability to ameliorate diabetic kidney damage

In this study, a p(AAPBA-b-Daidzein) block copolymer was designed and synthesised using glucose-responsive 3-acrylamidophenylboronic acid (AAPBA) and esterified daidzein as structural units; this copolymer possessed anti-diabetic pharmacological activity. After confirming the chemical structure of the copolymer, nanoparticles of the copolymer were prepared using the water-in-oil method. The results of the in vitro experiments showed that nanoparticles swelled when the pH was >7 or when the glucose concentration exceeded 1.0 mg/mL. Particle size measurements showed that the size of the nanoparticles was kept in the range of 100–300 nm before and after the glucose response, which helped avoid their clearance by the liver and kidneys. As the nanoparticles swelled, insulin and esterified daidzein were continuously released. The nanoparticles subcutaneously injected into mice with streptozotocin-induced diabetes were able to quickly and continuously reduce the blood sugar levels; significantly improve renal pathological damage and reduce renal function damage, inflammatory factors and oxidative stress indicators. In summary, the p(AAPBA-b-Daidzein) glucose-responsive nanoparticles prepared in the current study possess good pH value and glucose sensitivity, can achieve a precise and controlled release of insulin and exert the pharmacological activity of esterified daidzein. Therefore, it shows potential clinical application value in the treatment of diabetes and its complications.

Spatioselective Occlusion of Copolymer Nanoparticles within Calcite Crystals Generates Organic-Inorganic Hybrid Materials with Controlled Internal Structures.

Efficient occlusion of particulate additives into a single crystal has garnered an ever-increasing attention in materials science because it offers a counter-intuitive yet powerful platform to make crystalline nanocomposite materials with emerging properties. However, precisely controlling the spatial distribution of the guest additives within a host crystal remains highly challenging. We herein demonstrate a unique, straightforward method to engineer the spatial distribution of copolymer nanoparticles within calcite (CaCO3) single crystals by judiciously adjusting initial [Ca2+] concentration used for the calcite precipitation. More specifically, polymerization-induced self-assembly is employed to synthesize well-defined and highly anionic poly(3-sulfopropyl methacrylate potassium)41-block-poly(benzyl methacrylate)500 [PSPMA41-PBzMA500] diblock copolymer nanoparticles, which are subsequently used as model additives during the growth of calcite crystals. Impressively, such guest nanoparticles are preferentially occluded into specific regions of calcite depending on the initial [Ca2+] concentration. These unprecedented phenomena are most probably caused by dynamic change in electrostatic interaction between Ca2+ ions and PSPMA41 chains based on systematic investigations. This study not only showcases a significant advancement in controlling the spatial distribution of guest nanoparticles within host crystals, enabling the internal structure of composite crystals to be rationally tailored via a spatioselective occlusion strategy, but also provides new insights into biomineralization.

Spatioselective Occlusion of Copolymer Nanoparticles within Calcite Crystals Generates Organic‐Inorganic Hybrid Materials with Controlled Internal Structures

AbstractEfficient occlusion of particulate additives into a single crystal has garnered an ever‐increasing attention in materials science because it offers a counter‐intuitive yet powerful platform to make crystalline nanocomposite materials with emerging properties. However, precisely controlling the spatial distribution of the guest additives within a host crystal remains highly challenging. We herein demonstrate a unique, straightforward method to engineer the spatial distribution of copolymer nanoparticles within calcite (CaCO3) single crystals by judiciously adjusting initial [Ca2+] concentration used for the calcite precipitation. More specifically, polymerization‐induced self‐assembly is employed to synthesize well‐defined and highly anionic poly(3‐sulfopropyl methacrylate potassium)41‐block‐poly(benzyl methacrylate)500 [PSPMA41‐PBzMA500] diblock copolymer nanoparticles, which are subsequently used as model additives during the growth of calcite crystals. Impressively, such guest nanoparticles are preferentially occluded into specific regions of calcite depending on the initial [Ca2+] concentration. These unprecedented phenomena are most probably caused by dynamic change in electrostatic interaction between Ca2+ ions and PSPMA41 chains based on systematic investigations. This study not only showcases a significant advancement in controlling the spatial distribution of guest nanoparticles within host crystals, enabling the internal structure of composite crystals to be rationally tailored via a spatioselective occlusion strategy, but also provides new insights into biomineralization.

Crystallization-Driven Controlled 2D Self-Assemblies via Aqueous RAFT Emulsion Polymerization.

Aqueous emulsion polymerization is a robust technique for preparing nanoparticles of block copolymers; however, it typically yields spherical nanoassemblies. The scale preparation of nanoassemblies with nonspherical high-order morphologies is a challenge, particularly 2D core-shell nanosheets. In this study, the polymerization-induced self-assembly (PISA) and crystallization-driven self-assembly (CDSA) are combined to demonstrate the preparation of 2D nanosheets and their aggregates via aqueous reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization. First, the crucial crystallizable component for CDSA, hydroxyethyl methacrylate polycaprolactone (HPCL) macromonomer is synthesized by ring opening polymerization (ROP). Subsequently, the RAFT emulsion polymerization of HPCL is conducted to generate crystallizable nanomicelles by a grafting-through approach. This PISA process simultaneously prepared spherical latices and bottlebrush block copolymers comprising poly(N',N'-dimethylacrylamide)-block-poly(hydroxyethyl methacrylate polycaprolactone) (PDMA-b-PHPCL). The latexes are now served as seeds for inducing the formation of 2D hexagonal nanosheets, bundle-shaped and flower-like aggregation via the CDSA of PHPCL segments and unreacted HPCL during cooling. Electron microscope analysis trace the morphology evolution of these 2D nanoparticles and reveal that an appropriate crystallized component of PHPCL blocks play a pivotal role in forming a hierarchical structure. This work demonstrates significant potential for large-scale production of 2D nanoassemblies through RAFT emulsion polymerization.

Jeffamine-based diblock copolymer nanoparticles via reverse sequence polymerization-induced self-assembly in aqueous media

Jeffamines® are commercially available amine-capped poly (alkylene oxides) that have been used for various applications. In this study, a weakly hydrophobic monoamine-capped propylene oxide-rich Jeffamine® (M2005) is derivatized to introduce a trithiocarbonate end-group via amidation. This precursor is then dissolved using N,N′-dimethylacrylamide (DMAC), 2-(N-acryloyloxy)ethyl pyrrolidone (NAEP) or N-acryloylmorpholine (NAM) as a co-solvent to produce a concentrated aqueous reaction mixture containing 20 % w/w water. Subsequently, reversible addition-fragmentation chain transfer (RAFT) polymerization is used to prepare Jeffamine®-core diblock copolymer nanoparticles by reverse sequence polymerization-induced self-assembly (PISA). At intermediate conversion, additional degassed water is added and each polymerization continues to almost full conversion (>99 %) within 4 h at 60 °C, resulting in a 10–20 % w/w aqueous dispersion of sterically-stabilized Jeffamine®-core nanoparticles. Efficient chain extension of the Jeffamine® precursor is achieved in most cases and relatively narrow molecular weight distributions are obtained (Mw/Mn < 1.30) as judged by GPC analysis. Transmission electron microscopy studies confirm a polydisperse spherical morphology and dynamic light scattering studies report hydrodynamic diameters ranging from 145 to 312 nm. Finally, aqueous electrophoresis studies indicate essentially neutral nanoparticles over a wide range of solution pH, as expected for the three types of non-ionic steric stabilizer chains selected for this study.

Sub-micron colloidosomes with tuneable cargo release prepared using epoxy-functional diblock copolymer nanoparticles

HypothesisPickering emulsions stabilized using epoxy-functional block copolymer nanoparticles should enable the formation of sub-micron colloidosomes that are stable with respect to Ostwald ripening and allow tuneable small-molecule cargo release. ExperimentsEpoxy-functional diblock copolymer nanoparticles of 24 ± 4 nm were prepared via reversible addition-fragmentation chain transfer (RAFT)-mediated dispersion polymerization of methyl methacrylate (MMA) in n-dodecane. Sub-micron water-in-n-dodecane Pickering emulsions were prepared by high-pressure microfluidization. The epoxy groups were then ring-opened using 3-aminopropyltriethoxysilane (APTES) to prepare cross-linked colloidosomes. The colloidosomes survived removal of the aqueous phase using excess solvent. The silica shell thickness could be adjusted from 11 to 23 nm by varying the APTES/GlyMA molar ratio. The long-term stability of the colloidosomes was compared to precursor Pickering emulsions. Finally, the permeability of the colloidosomes was examined by encapsulation and release of a small molecule. FindingsThe Pickering emulsion droplet diameter was reduced from 700 to 200 nm by increasing the salt concentration within the aqueous phase. In the absence of salt, emulsion droplets were unstable due to Ostwald ripening. However, emulsions prepared with 0.5 M NaCl are stable for at least one month. The cross-linked colloidosomes demonstrated much more stable than the precursor sub-micron emulsions prepared without salt. The precursor nanoemulsions exhibited complete release (>99 %) of an encapsulated dye, while higher APTES/GlyMA ratios resulted in much lower dye release, yielding nearly impermeable silica capsules that retained around 95 % of the dye.

Oral co-polymeric raft-forming nano gels for targeted empagliflozin delivery against stomach cancer (SGC7901)

Empagliflozin (EMP) is known for its poor safety and efficacy profile due to its fast body distribution and poor solubility. Accordingly, an oral long-acting and floating/raft-forming nano gel was optimized to release coated EMP nanoparticles, and the released EMP nanoparticles showed enhanced dissolution compared to raw EMP particles. To repurpose EMP for cancer treatment, EMP shows anti-cancer and anti-inflammatory effects against cancer cells. EMP nanoparticles were characterized using FT-IR, PXRD, SEM, EMP encapsulation assay, and release studies. The raft-forming gel encapsulating the EMP was optimized and characterized. The EMP co-polymeric nanoparticles were studied to investigate EMP anti-cancer and anti-inflammatory activities against stomach cancer cells. The solubility of EMP nanoparticles was enhanced in 0.1 N HCl and pH 6.8 by 5 and 12 folds, respectively, compared to raw EMP powder. The particle size and zeta-potential values of improved EMP nanoparticles were 135.40 ± 18.60 nm, and −19.30 ± 0.80 mV, respectively. FT-IR, PXRD, SEM and TEM characterizations revealed polymeric coating of EMP particles. The study suggested that this optimized controlled-release raft-forming gel is a promising local oral approach against stomach cancer. The repurposing of EMP co-polymeric nanoparticles for stomach cancer and associated gastritis treatment was justified.

Light-Triggered Reversible Swelling of Azobenzene-Containing Block Copolymer Worms via Confined Deformation Prepared by Polymerization-Induced Self-Assembly.

Stimuli-responsive block copolymer nanoparticles (NPs) have received close attention in recent years owing to their tremendous application potential in smart materials. Azobenzene-containing NPs are widely studied due to the advantages of light as a stimulus and fast reversible trans-cis isomerization of azobenzene chromophores. However, the inefficient preparation process and difficult reversible transformation of morphologies limit their development. Herein it is demonstrated that the light-triggered reversible swelling behavior of wormlike NPs with high azobenzene content could be realized via confined deformation. These worms are prepared in large quantities via polymerization-induced self-assembly based on the copolymerization of 11-(4-(4-butylphenylazo)phenoxy)undecyl methacrylate (MAAz) and N-(methacryloxy)succinimide (NMAS) monomers. Upon UV/visible light irradiation, the reversible deformation of worms is achieved when the feed molar ratio of NMAS/MAAz is relatively high or via crosslinking using diamines, which leads to the reduction of the photoisomerization efficiency. The diameter variation of the worms is influenced by the amount and types of crosslinkers. Moreover, the scalability of this strategy is further proved by the fabrication of photo- and reductant-responsive crosslinked worms. It is expected that this study not only provides a new route to affording reversible photoresponsive NPs but also offers a unique insight into the reversible photodeformation mechanism of azobenzene-containing NPs.

Characterization of Mass, Diameter, Density, and Surface Properties of Colloidal Nanoparticles Enabled by Charge Detection Mass Spectrometry.

A variety of scattering-based, microscopy-based, and mobility-based methods are frequently used to probe the size distributions of colloidal nanoparticles with transmission electron microscopy (TEM) often considered to be the "gold standard". Charge detection mass spectrometry (CDMS) is an alternative method for nanoparticle characterization that can rapidly measure the mass and charge of individual nanoparticle ions with high accuracy. Two low polydispersity, ∼100 nm diameter nanoparticle size standards with different compositions (polymethyl methacrylate/polystyrene copolymer and 100% polystyrene) were characterized using both TEM and CDMS to explore the merits and complementary aspects of both methods. Mass and diameter distributions are rapidly obtained from CDMS measurements of thousands of individual ions of known spherical shape, requiring less time than TEM sample preparation and image analysis. TEM image-to-image variations resulted in a ∼1-2 nm range in the determined mean diameters whereas the CDMS mass precision of ∼1% in these experiments leads to a diameter uncertainty of just 0.3 nm. For the 100% polystyrene nanoparticles with known density, the CDMS and TEM particle diameter distributions were in excellent agreement. For the copolymer nanoparticles with unknown density, the diameter from TEM measurements combined with the mass from CDMS measurements enabled an accurate measurement of nanoparticle density. Differing extents of charging for the two nanoparticle standards measured by CDMS show that charging is sensitive to nanoparticle surface properties. A mixture of the two samples was separated based on their different extents of charging despite having overlapping mass distributions centered at 341.5 and 331.0 MDa.

Disulfide bonds as a molecular switch of enzyme-activatable anticancer drug precise release for fluorescence imaging and enhancing tumor therapy

Enzyme-activatable drug delivery systems have been developed for cancer diagnosis and therapy. However, targeted intracellular drug delivery is a challenge for precisely tumor imaging and therapy due to the increased stability of copolymer nanoparticles (NPs) is accompanied by a notable decrease in enzyme degradation. Herein, disulfide bond was designed as an enzyme-activatable molecular switch of SS-P(G2)2/DOX NPs. The copolymer NPs consists of polyvinylpyrrolidone (PVP) with disulfide bonds in the center and enzyme-degradable peptide dendrites (Phe-Lys) to form dendritic-linear-dendritic triblock copolymers (TBCs). The amphiphilic TBCs could be split into two identical amphiphilic diblock copolymers (DBCs) by glutathione (GSH) in cancer cells specifically while maintaining the same hydrophilic-lipophilic equilibrium. This structural transformation significantly reduced the stability of copolymer NPs and enhanced sensitivity of DOX release by cathepsin B-activated. Subsequently, the released DOX acted as an indicator of fluorescence imaging and chemotherapy drug for cancer cells. The polymeric NPs achieved excellent drug-loaded stability and prolonged blood circulation in vivo, and realized fluorescence imaging and specific cancer cell killing capabilities by responding to the overexpression of GSH and cathepsin B in tumor cells. Furthermore, the copolymer NPs demonstrated excellent blood compatibility and biosafety. Therefore, a novel strategy based on one tumor marker acting as the switch for another tumor microenvironment responsive drug delivery system could be designed for tumor intracellular imaging and chemotherapy.

Polymeric Micellar Nanoparticles Enable Image-guided Drug Delivery in Solid Tumors.

We report the development of a nanotechnology to co-deliver chemocoxib A with a reactive oxygen species (ROS)-activatable and COX-2 targeted pro-fluorescent probe, fluorocoxib Q (FQ) enabling real time visualization of COX-2 and CA drug delivery into solid cancers, using a di-block PPS 135 - b -POEGA 17 copolymer, selected for its intrinsic responsiveness to elevated reactive oxygen species (ROS), a key trait of the tumor microenvironment. FQ and CA were synthesized independently, then co-encapsulated within micellar PPS 135 - b -POEGA 17 co-polymeric nanoparticles (FQ-CA-NPs), and were assessed for cargo concentration, hydrodynamic diameter, zeta potential, and ROS-dependent cargo release. The uptake of FQ-CA-NPs in mouse mammary cancer cells and cargo release was assessed by fluorescence microscopy. Intravenous delivery of FQ-CA-NPs to mice harboring orthotopic mammary tumors, followed by vital optimal imaging, was used to assess delivery to tumors in vivo . The CA-FQ-NPs exhibited a hydrodynamic diameter of 109.2 ± 4.1 nm and a zeta potential (σ) of -1.59 ± 0.3 mV. Fluorescence microscopy showed ROS-dependent cargo release by FQ-CA-NPs in 4T1 cells, decreasing growth of 4T1 breast cancer cells, but not affecting growth of primary human mammary epithelial cells (HMECs). NP-derived fluorescence was detected in mammary tumors, but not in healthy organs. Tumor LC-MS/MS analysis identified both CA (2.38 nmol/g tumor tissue) and FQ (0.115 nmol/g tumor tissue), confirming the FQ-mediated image guidance of CA delivery in solid tumors. Thus, co-encapsulation of FQ and CA into micellar nanoparticles (FQ-CA-NPs) enabled ROS-sensitive drug release and COX-2-targeted visualization of solid tumors.

Development and Evaluation of Stable Long Circulating Decitabine-loaded Copolymeric Nanoparticles: Harnessing QbD Approach and Lyophilization Technique

Development and Evaluation of Stable Long Circulating Decitabine-loaded Copolymeric Nanoparticles: Harnessing QbD Approach and Lyophilization Technique

Amphiphilic N-halamine copolymer antibacterial nanoparticles with hydrogen-donor and hydrogen-acceptor

Bacterial contamination in water bodies is potentially transmissible to humans, making water bodies a major pathway of bacterial transmission. However, existing hydantoin copolymer nanoparticles did not achieve the regulation of nanoparticle dispersion and particle size by adjusting the ratio of hydrogen-donors and hydrogen-acceptors. To tackle this issue, amphiphilic hydantoin copolymer nanoparticles (P(VBDH-BA-NVP)NPs) were synthesized by modulating hydrogen-donors and hydrogen-acceptors using emulsion polymerization, and amphiphilic N-halamine copolymer nanoparticles (P(ClV-BA-NVP)NPs) were subsequently prepared via chlorination treatment. Impressively, nanoparticle dispersion and particle size were modulated by adjusting the ratio of hydrogen-donors and hydrogen-acceptors. With the increase of nanoparticle dispersion and the decrease of particle size, the active chlorine content was gradually enlarged, and the antibacterial performance was progressively enhanced against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). More importantly, amphiphilic N-halamine copolymer nanoparticles with two-dimensional dispersing (2DD-P(ClV-BA-NVP)NPs) exhibited excellent antibacterial properties, which benefited from the dual coordination of direct contact killing and indirect release killing in aqueous medium. Through designing P(VBDH-BA-NVP)NPs with hydrogen bond interactions, this approach aims to achieve the constitutive relationship between the effective exposure of active sites and the antibacterial effect.

Usefulness of percutaneous estradiol-loaded PLGA-PEG-PLGA nanoparticles for the treatment of osteoporosis

Compared with poly (dl-lactide-co-glycolide) (PLGA) nanoparticles, triblock copolymer (PLGA-PEG-PLGA) nanoparticles composed of PLGA and polyethylene glycol (PEG) may improve the skin permeability of drugs. In this study, the usefulness of estradiol-loaded (E2-loaded) PLGA-PEG-PLGA nanoparticles in the treatment of osteoporosis was investigated by comparison with E2-loaded PLGA nanoparticles. The cumulative E2 permeation of each nanoparticle through rat skin was quantified using a Franz cell. The results showed that PLGA-PEG-PLGA nanoparticles had significantly higher permeation than PLGA nanoparticles. Next, in vivo treatment experiments were conducted using an ovariectomized rat model of osteoporosis. Nanoparticles were administered once per week in combination with iontophoresis. At 6 weeks after the initiation of treatment, significant improvement in bone density was observed in the treated group compared with the untreated group. The improvement in bone density tended to be greater in the PLGA-PEG-PLGA nanoparticle group versus the PLGA nanoparticle group. This may be attributed to the higher hydrophilicity of the particle surface of PLGA-PEG-PLGA nanoparticles compared with PLGA nanoparticles and the improved skin permeability of the particles through the trans-adnexal pathway.

Arginine-Functional Methacrylic Block Copolymer Nanoparticles: Synthesis, Characterization, and Adsorption onto a Model Planar Substrate.

Recently, we reported the synthesis of a hydrophilic aldehyde-functional methacrylic polymer (Angew. Chem., 2021, 60, 12032-12037). Herein we demonstrate that such polymers can be reacted with arginine in aqueous solution to produce arginine-functional methacrylic polymers without recourse to protecting group chemistry. Careful control of the solution pH is essential to ensure regioselective imine bond formation; subsequent reductive amination leads to a hydrolytically stable amide linkage. This new protocol was used to prepare a series of arginine-functionalized diblock copolymer nanoparticles of varying size via polymerization-induced self-assembly in aqueous media. Adsorption of these cationic nanoparticles onto silica was monitored using a quartz crystal microbalance. Strong electrostatic adsorption occurred at pH 7 (Γ = 14.7 mg m-2), whereas much weaker adsorption occurred at pH 3 (Γ = 1.9 mg m-2). These findings were corroborated by electron microscopy, which indicated a surface coverage of 42% at pH 7 but only 5% at pH 3.

Dual lanthanide Complexes-Loaded ratiometric nanothermometer for elucidating intracellular variations of temperature and calcium transport

Herein, we report a ratiometric nanothermometer to study the correlation of heat/temperature and intracellular calcium transport. Firstly, poly(methyl methacrylate)-based copolymeric nanoparticles (NPs) from nanoprecipitation encapsulates two lanthanide complexes (Eu(DNPD)3Phen and Sm(DBM)3Phen) to enhance fluorescence of lanthanide ions (Ln3+). NPs were thereafter coated with an amphiphilic block copolymer pluronic F-127 to prevent nonspecific interaction between NPs and proteins, which ensures internalization of the nanothermometer into living cells. The back energy transfer (BET) from the excited state of Ln3+ to the triplet energy levels of ligand endows the temperature dependence on ratiometric fluorescence of Eu3+ and Sm3+. This nanothermometer has excellent anti-interference ability, ensuring accurate cell temperature measurement within a range of 29.0–40.0℃. It exhibits a maximum relative thermal sensitivity of 1.9 % ℃-1 at 29.0℃ and a minimum temperature resolution of 0.1℃ at 39.0℃ in live HeLa cells. The nanothermometer was applied for studying temperature or heat induced intracellular Ca2+ transport. It illustrated that free cytoplasmic Ca2+ concentration ([Ca2+]i) increased only when the cell temperature reached a certain threshold under photothermal stimulation, and the rise of temperature corresponds to the increase of [Ca2+]i. Furthermore, Ca2+ burst induced Ca2+ transport from cytoplasm to endoplasmic reticulum, which promoted ATP hydrolysis along with the rise of intracellular temperature. 200 s stimulation with FCCP enhanced ca. 1.7℃ of intracellular temperature along with 2.2 folds increment of [Ca2+]i, as FCCP induces Ca2+ efflux from mitochondria by increasing proton concentration therein. These results indicate that a close relationship between intracellular temperature and Ca2+ transport, which is of great significance for further understanding the role of temperature in signaling pathways and neurotransmitter release events.

Grafting Block Copolymer Nanoparticles to a Surface via Aqueous Photoinduced Polymerization-induced Self-Assembly at Room Temperature.

The creation of well-defined surface nanostructures is important for a diverse set of applications such as cell adhesion, superhydrophobic coating, and lithography. In this study, we describe a robust bottom-up method for surface functionalization that involves surface-initiated reversible deactivation radical polymerization (RDRP) and the grafting of block copolymer nanoparticles to material surfaces via aqueous photoinduced polymerization-induced self-assembly (photo-PISA) at room temperature. Using silica nanoparticles as a model substrate, colloidal mesoscale hybrid assemblies with various morphologies were successfully prepared. The morphologies can be easily tuned by changing the lengths of macromolecular chain transfer agents and parameters of the silica nanoparticles. The surface-initiated photo-PISA approach can also be employed for other large-scale substrates such as silicon wafer. Taking advantage of mild reaction conditions of this method (room temperature, aqueous medium, and visible light), enzymatic deoxygenation was introduced to develop oxygen-tolerant surface-initiated photo-PISA that can fabricate well-defined nanostructures on large-scale substrates under open-to-air conditions.