Role of EPAC1 in chronic pain.

Chronic pain usually lasts over three months and commonly occurs in chronic diseases (cancer, arthritis, and diabetes), injuries (herniated discs, torn ligaments), and many major pain disorders (neuropathic pain, fibromyalgia, chronic headaches). Unfortunately, there is currently a lack of effective treatments to help people with chronic pain to achieve complete relief. Therefore,it is particularly important to understand the mechanism of chronic pain and find new therapeutic targets. The exchange protein directly activated by cyclic adenosine monophosphate(cAMP) (EPAC) has been recognized for its functions in nerve regeneration, stimulating insulin release, controlling vascular pressure, and controlling other metabolic activities. In recent years, many studies have found that the subtype of EPAC, EPAC1 is involved in the regulation of neuroinflammation and plays a crucial role in the regulation of pain, which is expected to become a new therapeutic target for chronic pain. This article reviews the major contributions of EPAC1 in chronic pain.

Aerodynamic effects cause higher forest evapotranspiration and water yield reductions after wildfires in tall forests.

Wildfires are increasing in frequency, intensity, and extent globally due to climate change and they can alter forest composition, structure, and function. The destruction and subsequent regrowth of young vegetation can modify the ecosystem evapotranspiration and downstream water availability. However, the response of forest recovery on hydrology is not well known with even the sign of evapotranspiration and water yield changes following forest fires being uncertain across the globe. Here, we quantify the effects of forest regrowth after catastrophic wildfires on evapotranspiration and runoff in the world's tallest angiosperm forest (Eucalyptus regnans) in Australia. We combine eddy covariance measurements including pre- and post-fire periods, mechanistic ecohydrological modeling and then extend the analysis spatially to multiple fires in eucalypt-dominated forests in south-eastern Australia by utilizing remote sensing. We find a fast recovery of evapotranspiration which reaches and exceeds pre-fire values within 2 years after the bushfire, a result confirmed by eddy covariance data, remote sensing, and modeling. Such a fast evapotranspiration recovery is likely generalizable to tall eucalypt forests in south-eastern Australia as shown by remote sensing. Once climate variability is discounted, ecohydrological modeling shows evapotranspiration rates from the recovering forest which reach peak values of +20% evapotranspiration 3 years post-fire. As a result, modeled runoff decreases substantially. Contrary to previous research, we find that the increase in modeled evapotranspiration is largely caused by the aerodynamic effects of a much shorter forest height leading to higher surface temperature, higher humidity gradients and therefore increased transpiration. However, increases in evapotranspiration as well as decreases in runoff caused by the young forest are constrained by energy and water limitations. Our result of an increase in evapotranspiration due to aerodynamic warming in a shorter forest after wildfires could occur in many parts of the world experiencing forest disturbances.

Political embeddedness in public-private partnership for nature conservation: A land trust reserve case from China.

Private sector plays an increasingly vital role in nature conservation globally. This study explores the concept of political embeddedness, which suggests that governments and environmental nongovernmental organizations (ENGOs) can leverage each other's strengths to achieve both formal and informal goals. Using the case of Laohegou Nature Reserve in China, this study illustrated how the complementary advantages of the government and ENGOs form the foundation of a land trust reserve. Within the case, the study found that power and interest balance between the government and ENGOs during project implementation supported their formal cooperation in nature conservation. This study proposed a political perspective to elaborate power and interest in the formal and informal dimensions of nature conservation public-private partnership (PPP) project. Moreover, it noted that a balance of power between the government and ENGOs is essential in building partnership networks with inclusive interests.

Optical design algorithm utilizing continuous-discrete variables grounded on stochastic processes.

This work proposes an optimization algorithm in optical design based on the concepts of ergodic and stochastic processes in statistical mechanics. In mixed-variable optimization problems, pseudo-random number and discrete-to-continuous variable conversion dramatically increase the speed at which the system solves for the optimal solution. Pseudo-random numbers are mainly applied in two important steps in the optimization algorithm: determining the combination of glasses involved and the order in which the successive glass parameters are replaced by real glasses. After two series of stochastic processes, the merit function value decreases rapidly along the steepest descent path, and thus the optical system approaches the optimal solution within a very short duration of time. By using the method proposed in this paper, a plan apochromatic objective with a long working distance was optimized, and finally, a high-quality optical system was obtained.

Remotely sensed evidence of the divergent climate impacts of wind farms on croplands and grasslands.

To mitigate climate change, the utilization of wind energy has rapidly expanded over the last two decades. However, when producing clean electricity, wind farms (WFs) may in turn alter the local climate by interfering in land surface-atmosphere interactions. Currently, China and the United States have the highest wind energy capacities globally. Thus, quantitatively analyzing the impacts of WFs on land surface temperature (LST) between the two countries is valuable to deeply understand the climate impact of WF. In this study, we use the moderate-resolution imaging spectroradiometer (MODIS) time series from 2001 to 2018 to reveal the impacts of 186 WFs (76 in China and 110 in the US) on local LSTs. The remote sensing observations reveal that WFs generally lead to warming impacts in both countries, with stronger effects in the US compared to China. During the daytime, WFs in the US exhibit a significant warming effect of 0.08 °C (p < 0.05), while the impact in China is nonsignificant (0.06 °C, p = 0.15). At night, the warming impacts in the US are approximately 1.7 times greater than in China (0.19 °C vs. 0.11 °C). Differences in the LST impacts between the two countries are primarily driven by cropland WFs, which cause more significant cooling effects in China (-0.34 °C in the daytime and - 0.19 °C at night, p < 0.01) compared to the US. However, these differences are not significant for grassland WFs. Moreover, the impacts of WFs on croplands' LSTs are strongly correlated with their evapotranspiration impacts, likely influenced by irrigation practices. In addition to evapotranspiration, a machine learning model suggests that background climate and terrain factors can alter the LST impacts. Our observations in the two largest WF-deployment countries provide a new understanding of the climate impacts of WFs, which should be considered in the fields of wind and renewable energy deployment.

A sentiment analysis approach for travel-related Chinese online review content.

Using technology for sentiment analysis in the travel industry can extract valuable insights from customer reviews. It can assist businesses in gaining a deeper understanding of their consumers' emotional tendencies and enhance their services' caliber. However, travel-related online reviews are rife with colloquialisms, sparse feature dimensions, metaphors, and sarcasm. As a result, traditional semantic representations of word vectors are inaccurate, and single neural network models do not take into account multiple associative features. To address the above issues, we introduce a dual-channel algorithm that integrates convolutional neural networks (CNN) and bi-directional long and short-term memory (BiLSTM) with an attention mechanism (DC-CBLA). First, the model utilizes the pre-trained BERT, a transformer-based model, to extract a dynamic vector representation for each word that corresponds to the current contextual representation. This process enhances the accuracy of the vector semantic representation. Then, BiLSTM is used to capture the global contextual sequence features of the travel text, while CNN is used to capture the richer local semantic information. A hybrid feature network combining CNN and BiLSTM can improve the model's representation ability. Additionally, the BiLSTM output is feature-weighted using the attention mechanism to enhance the learning of its fundamental features and lessen the influence of noise features on the outcomes. Finally, the Softmax function is used to classify the dual-channel fused features. We conducted an experimental evaluation of two data sets: tourist attractions and tourist hotels. The accuracy of the DC-CBLA model is 95.23% and 89.46%, and that of the F1-score is 97.05% and 93.86%, respectively. The experimental results demonstrate that our proposed DC-CBLA model outperforms other baseline models.

Satellite-based evidence highlights a considerable increase of urban tree cooling benefits from 2000 to 2015.

Tree planting is a prevalent strategy to mitigate urban heat. Tree cooling efficiency (TCE), defined as the temperature reduction for a 1% tree cover increase, plays an important role in urban climate as it regulates the capacity of trees to alter the surface energy and water budget. However, the spatial variation and more importantly, temporal heterogeneity of TCE in global cities are not fully explored. Here, we used Landsat-based tree cover and land surface temperature (LST) to compare TCEs at a reference air temperature and tree cover level across 806 global cities and to explore their potential drivers with a boosted regression tree (BRT) machine learning model. From the results, we found that TCE is spatially regulated by not only leaf area index (LAI) but climate variables and anthropogenic factors especially city albedo, without a specific variable dominating the others. However, such spatial difference is attenuated by the decrease of TCE with tree cover, most pronounced in midlatitude cities. During the period 2000-2015, more than 90% of analyzed cities showed an increasing trend in TCE, which is likely explained by a combined result of the increase in LAI, intensified solar radiation due to decreased aerosol content, increase in urban vapor pressure deficit (VPD) and decrease of city albedo. Concurrently, significant urban afforestation occurred across many cities showing a global city-scale mean tree cover increase of 5.3 ± 3.8% from 2000 to 2015. Over the growing season, such increases combined with an increasing TCE were estimated to on average yield a midday surface cooling of 1.5 ± 1.3°C in tree-covered urban areas. These results are offering new insights into the use of urban afforestation as an adaptation to global warming and urban planners may leverage them to provide more cooling benefits if trees are primarily planted for this purpose.

Detecting formal and informal interests in forest governance.

To reveal the interests of actors in forest governance, this paper proposes a power-based interest identification (PII) approach. Based on the assumption of intentional action, the benefits that actors derive from policy impacts are the result of interest-driven actions. This paper further proposes a theoretical definition of interests that includes formal goals at the social and ecological levels, as well as informal political, economic, and strategic interests. Researchers need to identify powerful actors by identifying power mechanisms and resources, and can then observe actors' formal goals through interviews and documents. For informal interests, the actor observes the informal gains of powerful actors in policy impacts, which are then coded according to political, economic, and strategic interests. Combining these steps, actors can infer the formal and informal interests of powerful actors.•Researchers can verify actors' formal objectives by interview and documents.•Among policy impacts, researchers can observe influences at the social and ecological levels, as well as changes in actors' control, economic gains, and dissemination of ideas.•Researchers can infer informal interests of powerful actors from observation of policy impacts.

High-Strength Hydrogel Attachment through Nanofibrous Reinforcement.

The repair of a cartilage lesion with a hydrogel requires a method for long-term fixation of the hydrogel in the defect site. Attachment of a hydrogel to a base that allows for integration with bone can enable long-term fixation of the hydrogel, but current methods of forming bonds to hydrogels have less than a tenth of the shear strength of the osteochondral junction. This communication describes a new method, nanofiber-enhanced sticking (NEST), for bonding a hydrogel to a base with an adhesive shear strength three times larger than the state-of-the-art. An example of NEST is described in which a nanofibrous bacterial cellulose sheet is bonded to a porous base with a hydroxyapatite-forming cement followed by infiltration of the nanofibrous sheet with hydrogel-forming polymeric materials. This approach creates a mineralized nanofiber bond that mimics the structure of the osteochondral junction, in which collagen nanofibers extend from cartilage into a mineralized region that anchors cartilage to bone.

Antifouling Surfaces Enabled by Surface Grafting of Highly Hydrophilic Sulfoxide Polymer Brushes.

Antifouling surfaces are important in a broad range of applications. An effective approach to antifouling surfaces is to covalently attach antifouling polymer brushes. This work reports the synthesis of a new class of antifouling polymer brushes based on highly hydrophilic sulfoxide polymers by surface-initiated photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization. The sulfoxide polymer brushes are able to effectively reduce nonspecific adsorption of proteins and cells, demonstrating remarkable antifouling properties. Given the outstanding antifouling behavior of the sulfoxide polymers and versatility of surface-initiated PET-RAFT technology, this work presents a useful and general approach to engineering various material surfaces with antifouling properties, for potential biomedical applications in areas such as tissue engineering, medical implants, and regenerative medicine.

Low-Fouling Fluoropolymers for Bioconjugation and In†Vivo Tracking.

The conjugation of hydrophilic low-fouling polymers to therapeutic molecules and particles is an effective approach to improving their aqueous stability, solubility, and pharmacokinetics. Recent concerns over the immunogenicity of poly(ethylene glycol) has highlighted the importance of identifying alternative low fouling polymers. Now, a new class of synthetic water-soluble homo-fluoropolymers are reported with a sulfoxide side-chain structure. The incorporation of fluorine enables direct imaging of the homopolymer by 19 F MRI, negating the need for additional synthetic steps to attach an imaging moiety. These self-reporting fluoropolymers show outstanding imaging sensitivity and remarkable hydrophilicity, and as such are a new class of low-fouling polymer for bioconjugation and in vivo tracking.

Light-Induced ROS Generation and 2-DG-Activated Endoplasmic Reticulum Stress by Antitumor Nanosystems: An Effective Combination Therapy by Regulating the Tumor Microenvironment.

A multimodal cancer therapeutic nanoplatform is reported. It demonstrates a promising approach to synergistically regulating the tumor microenvironment. The combination of intracellular reactive oxygen species (ROS) generated by irradiation of photosensitizer and endoplasmic reticulum (ER) stress induced by 2-deoxy-glucose (2-DG) has a profound effect on necrotic or apoptotic cell death. Especially, targeting metabolic pathway by 2-DG is a promising strategy to promote the effect of photodynamic therapy and chemotherapy. The nanoplatform can readily release its cargoes inside cancer cells and combines the advantages of ROS-sensitive releasing chemotherapeutic drugs, upregulating apoptosis pathways under ER stress, light-induced generation of cytotoxic ROS, achieving tumor accumulation, and in vivo fluorescence imaging capability. This work highlights the importance of considering multiple intracellular stresses as design parameters for nanoscale functional materials in cell biology, immune response, as well as medical treatments of cancer, Alzheimer's disease, etc.

Correlation between Drug Loading Content and Biological Activity: The Complexity Demonstrated in Paclitaxel-Loaded Glycopolymer Micelle System.

Drug delivery carriers are now widely established because they can increase the therapeutic efficiency of drugs. In general, the aim in this field is to create effective carriers that have large amounts of drugs loaded to minimize drug carrier material that needs to be disposed of. However, there has been little attention so far in the literature on the effect of the amount of loaded drugs on the biological activity. In this paper, we are trying to answer the question of how the drug-loading content will affect the in vitro activity. We use two methods to load paclitaxel (PTX) into micelles based on the glycopolymer, poly(1- O-methacryloyl-ß-d-fructopyranose)- block-poly(methyl methacylate) (Poly(1- O-MAFru)35- b-PMMA145). In the one-step method, the drug is loaded into the particles during the self-assembly process. However, the size of nanoparticle increased with the PTX content from 26 to 50 nm, triggering enhanced cellular uptake by MCF-7 and MDA-MB-231, which was caused by changes in diameter size and not by changes in drug concentration. To keep the nanoparticle size constant, preformed micelles were loaded with PTX (two-step process). The increasing amount of loaded drug led to decreased cellular uptake and reduced cytotoxicity by the cancer cell lines. Small-angle neutron scattering and small-angle X-ray scattering, supported by transmission electron microscopy and dynamic light scattering, exposed the PTX location in the shell. This caused shrinkage of the shell and lower levels of shell hydration, resulting in lower cellular uptake and lower cytotoxicity. Upon the release of PTX, the shell regained its original level of hydration. We could show that because drug loading causes morphology changes, in either the shell or the size, it is impossible to separate the parameters that will influence the biological activity. Although the same phenomenon may not apply to every drug delivery system, it needs to be considered that except for the well-known parameters that affect cell uptake-size, shape, surface chemistry, type of nanoparticle, and presence of bioactive groups-the amount of loaded drugs might change the physicochemical parameters of the nanoparticle and thus the in vitro and potentially the in vivo outcomes.

Just add sugar for carbohydrate induced self-assembly of curcumin.

In nature, self-assembly processes based on amphiphilic molecules play an integral part in the design of structures of higher order such as cells. Among them, amphiphilic glycoproteins or glycolipids take on a pivotal role due to their bioactivity. Here we show that sugars, in particular, fructose, are capable of directing the self-assembly of highly insoluble curcumin resulting in the formation of well-defined capsules based on non-covalent forces. Simply by mixing an aqueous solution of fructose and curcumin in an open vessel leads to the generation of capsules with sizes ranging between 100 and 150 nm independent of the initial concentrations used. Our results demonstrate that hydrogen bonding displayed by fructose can induce the self-assembly of hydrophobic molecules such as curcumin into well-ordered structures, and serving as a simple and virtually instantaneous way of making nanoparticles from curcumin in water with the potential for template polymerization and nanocarriers.

Multihydroxy-Anthraquinone Derivatives as Free Radical and Cationic Photoinitiators of Various Photopolymerizations under Green LED.

Multihydroxy-anthraquinone derivatives [i.e., 1,2,4-trihydroxyanthraquinone (124-THAQ), 1,2,7-trihydroxyanthraquinone (127-THAQ), and 1,2,5,8-tetrahydroxyanthraquinone (1258-THAQ)] can interact with various additives [e.g., iodonium salt, tertiary amine, N-vinylcarbazole, and 2-(4-methoxystyryl)-4,6-bis(trichloromethyl)-1,3,5-triazine] under household green LED irradiation to generate active species (cations and radicals). The relevant photochemical mechanism is investigated using quantum chemistry, fluorescence, cyclic voltammetry, laser flash photolysis, steady state photolysis, and electron spin resonance spin-trapping techniques. Furthermore, the multihydroxy-anthraquinone derivative-based photoinitiating systems are capable of initiating cationic photopolymerization of epoxides or divinyl ethers under green LED, and the relevant photoinitiation ability is consistent with the photochemical reactivity (i.e., 124-THAQ-based photoinitiating system exhibits highest reactivity and photoinitiation ability). More interestingly, multihydroxy-anthraquinone derivative-based photoinitiating systems can initiate free radical crosslinking or controlled (i.e., reversible addition-fragmentation chain transfer) photopolymerization of methacrylates under green LED. It reveals that multihydroxy-anthraquinone derivatives can be used as versatile photoinitiators for various types of photopolymerization reactions.

Delivery of Amonafide from Fructose-Coated Nanodiamonds by Oxime Ligation for the Treatment of Human Breast Cancer.

The introduction of a strategy toward polymer/nanodiamond hybrids with high polymer grafting density and accessible polymer structural characterization is of critical importance for nanodiamonds' surface modification and bioagent attachment for their biomedical application. Here, we report a glycopolymer/nanodiamond hybrid drug delivery system, which was prepared by grafting amonafide-conjugated glycopolymers onto the surface of nanodiamonds via oxime ligation. Poly(1-O-methacryloyl-2,3:4,5-di-O-isopropylidene-ß-d-fructopyranose)-b-poly(3-vinylbenzaldehyde-co-methyl methacrylate), featuring pendant aldehyde groups, is prepared via RAFT polymerization. The anticancer drug amonafide is conjugated to the polymer chains via imine chemistry, resulting in acid-degradable imine linkages. The obtained amonafide-conjugated glycopolymers are subsequently grafted onto the surface of aminooxy-functionalized nanodiamonds via oxime ligation. The molecular weight of the conjugated polymers is characterized by size-exclusion chromatography (SEC), while the successful conjugation and corresponding grafting density is assessed by nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric aanalysis (TGA). Our results indicate that the mass percentage of amonafide in the polymer chains is around 17% and the surface density of polymer chains is 0.24 molecules/nm2. The prepared drug delivery system has a hydrodynamic size around 380 nm with low PDI (0.3) and can effectively deliver amonafide into breast cancer cell and significantly inhibit the cancer cell viability. In 2D cell culture models, the IC50 values of ND-Polymer-AMF delivery system (7.19 µM for MCF-7; 4.92 µM for MDA-MB-231) are lower than those of free amonafide (11.23 µM for MCF-7; 13.98 µM for MDA-MB-231). An inhibited cell viability of nanodiamonds/polymer delivery system is also observed in 3D spheroids' models, suggesting that polymer-diamonds hybrid materials can be promising platforms for breast cancer therapy.

Length vs. stiffness: which plays a dominant role in the cellular uptake of fructose-based rod-like micelles by breast cancer cells in 2D and 3D cell culture models?

Polymeric nanoparticles with long circulation time hold great promise for anti-cancer drug delivery. An enhanced circulation effect of rod-like micelles has been reported, yet efficient intracellular delivery, especially their interactions with cells during endocytosis, still remains inconsistent. Internalization of rod-like nanoparticles is significantly affected by a number of factors including aspect ratio, stiffness and surface chemistry of nanoparticles. Our previous research has shown that the length of rods affected their cellular uptake by breast cancer cells. Here, the influence of rod stiffness in cellular uptake was investigated to provide a comprehensive understanding of the interaction between rods and cells during endocytosis. Well-defined fructose-coated rod-like micelles of different lengths and stiffness were prepared successfully. The AFM results indicate that rods based on poly(1-O-MAFru)31-b-PMMA166 are significantly stiffer than those prepared from poly(1-O-MAFru)31-b-PBA158. The cellular uptake of these different rod-like micelles by breast cancer cells was investigated. In vitro studies via 2D and 3D cell culture models reveal that stiffer rods exhibit a higher cellular uptake and a deeper penetration into cells than the soft rod-like micelles. These results indicate that the internalization of rod-like micelles is significantly affected by their stiffness, though the length of rods also plays an important role. Our results yield a fundamental understanding of the stiffness effect of rod-like micelles on cellular uptake.

PEG Grafted-Nanodiamonds for the Delivery of Gemcitabine.

Carboxyl end-functionalized poly[poly(ethylene glycol) methyl ether methacrylate] [P(PEGMEMA)] and its block copolymer with gemcitabine substituted poly(N-hydroxysuccinimide methacrylate) [PGem-block-P(PEGMEMA)] are synthesized via reversible addition-fragmentation transfer (RAFT) polymerization. Then, two polymers are grafted onto the surface of amine-functionalized nanodiamonds to obtain [P(PEGMEMA)]-grafted nanodiamonds (ND-PEG) and [PGem-block-P(PEGMEMA)]-grafted nanodiamonds (ND-PF). Gemcitabine is physically absorbed to ND-PEG to produce ND-PEG (Gem). Two polymer-grafted nanodiamonds (i.e., with physically absorbed gemcitabine ND-PEG (Gem) and with chemically conjugated gemcitabine ND-PF) are characterized using attenuated total reflectance infrared spectroscopy, dynamic light scattering, and thermogravimetric analysis. The drug release, cytotoxicity (to seed human pancreatic carcinoma AsPC-1 cells), and cellular uptake of ND-PEG (Gem) and ND-PF are also investigated.

Fructose-Coated Nanodiamonds: Promising Platforms for Treatment of Human Breast Cancer.

Well-defined carboxyl end-functionalized glycopolymer Poly(1-O-methacryloyl-2,3:4,5-di-O-isopropylidene-ß-d-fructopyranose) (Poly(1-O-MAipFru)62) has been prepared via reversible addition-fragmentation chain transfer polymerization and grafted onto the surface of amine-functionalized nanodiamonds via a simple conjugation reaction. The properties of the nanodiamond-polymer hybrid materials ND-Poly(1-O-MAFru)62 are investigated using infrared spectroscopy, thermogravimetric analysis, dynamic light scattering, and transmission electron microscopy. The dispersibility of the nanodiamonds in aqueous solutions is significantly improved after the grafting of the glycopolymer. More interestingly, the cytotoxicity of amine-functionalized nanodiamonds is significantly decreased after decoration with the glycopolymer even at a high concentration (125 µg/mL). The nanodiamonds were loaded with doxorubicin to create a bioactive drug delivery carrier. The release of doxorubicin was faster in media of pH 5 than media of pH 7.4. The nanodiamond drug delivery systems with doxorubicin are used to treat breast cancer cells in 2D and 3D models. Although the 2D cell culture results indicate that all nanodiamonds-doxorubicin complexes are significantly less toxic than free doxorubicin, the glycopolymer-coated nanodiamonds-doxorubicin show higher cytotoxicity than free doxorubicin in the 3D spheroids after treatment for 8 days. The enhanced cytotoxicity of Poly(1-O-MAFru)62-ND-Dox in 3D spheroids may result from the sustained drug release and deep penetration of these nanocarriers, which play a role as a "Trojan Horse". The massive cell death after 8-day incubation with Poly(1-O-MAFru)62-ND-Dox demonstrates that glycopolymer-coated nanodiamonds can be promising platforms for breast cancer therapy.

Cellular Uptake and Movement in 2D and 3D Multicellular Breast Cancer Models of Fructose-Based Cylindrical Micelles That Is Dependent on the Rod Length.

While the shape effect of nanoparticles on cellular uptake has been frequently studied, no consistent conclusions are available currently. The controversy mainly focuses on the cellular uptake of elongated (i.e., filaments or rod-like micelles) as compared to spherical (i.e., micelles and vesicles) nanoparticles. So far, there is no clear trend that proposes the superiority of spherical or nonspherical nanoparticles with conflicting reports available in the literature. One of the reasons is that these few reports available deal with nanoparticles of different shapes, surface chemistries, stabilities, and aspects ratios. Here, we investigated the effect of the aspect ratio of cylindrical micelles on the cellular uptake by breast cancer cell lines MCF-7 and MDA-MB-231. Cylindrical micelles, also coined rod-like micelles, of various length were prepared using fructose-based block copolymers poly(1-O-methacryloyl-ß-d-fructopyranose)-b-poly(methyl methacrylate). The critical water content, temperature, and stirring rate that trigger the morphological transition from spheres to rods of various aspect ratios were identified, allowing the generation of different kinetically trapping morphologies. High shear force as they are found with high stirring rates was observed to inhibit the formation of long rods. Rod-like micelles with length of 500-2000 nm were subsequently investigated toward their ability to translocate in breast cancer cells and penetrate into MCF-7 multicellular spheroid models. It was found that shorter rods were taken up at a higher rate than longer rods.