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The mechanism for protein stabilization or destabilization has long been an open quest. In the present study, we have studied the interactions between amino acids and guanidinium (Gdm+)/ammonium (NH4+) ions by using low field nuclear magnetic resonance (LF-NMR), where Gdm+ and NH4+ are denaturant and stabilizer for proteins, respectively. It shows that Gdm+ favors to bind to the thiol group or the hydroxyl group on the side chain but weakly interacts with the α-carboxyl group. In contrast, NH4+ prefers to bind to the α-carboxyl group but slightly interacts with the thiol group or the hydroxyl group on the side chain of amino acids. 1HNMR reveals the hydrogen bonding between NH4+ and the α-carboxyl group, which is not involved in the interactions between Gdm+ and cysteine. Our study demonstrates that the strong interactions between the denaturant and the sulfur atom or the disulfide bond promote the direct binding of the denaturant toward proteins, leading to the destabilization.

Owing to the convenient and visual advantages, dye mapping agents are the most popular lymph tracing agents in the current clinic practices. However, limit tissue penetration always leads to hardly detect deeper lymph nodes (LNs), such as regional lymph nodes (RLNs). Therefore, exploring multimodal nanotheranostic agents for diagnosis and treatment of metastatic LNs are desired. In this study, polydopamine-encapsulated gadolinium-loaded multi-walled carbon nanotube (MWCNT-Gd@PDA) were strategically designed for dual-modality mapping guided photothermal therapy (PTT) by positive signal of magnetic resonance imaging (MRI) as well as deep black of the nanomaterials providing visual information. PDA, with excellent biocompatibility and biodegradability, can be easily deposited on many kinds of inorganic and organic materials to prepare functional materials. In order to prevent gadolinium ion escaping from the MWCNT, PDA shell was coated on the surface of MWCNT-Gd. Thus, the prepared MWCNT-Gd@PDA nanomaterials were lack of inherent biological toxicity. More importantly, under the guidance of dual-modality mapping, we demonstrated that primary tumors and RLNs could be simultaneously and effectively ablated by near-infrared irradiation to acquire the radical photothermal dissection. The results showed that our nanosystem possessed the precise spatial-temporal selectivity in comparison with conventional surgery and T2-MRI guided PTT.

Carbonaceous dots (CDs) are superior nanomaterials owing to their promising luminescence properties and good biocompatibility. However, most CDs have relatively short excitation/emission, which restrict their application in bioimaging. In this study, a simple one-step procedure was developed for synthesis of melanin-originated CDs (MNPs). The MNPs showed two long red shift emissions at 570 nm and 645 nm with broad absorptions from 200 nm to 400 nm and 500 nm to 700 nm, suggesting the great potential of MNPs in bioimaging. Besides, several experiments indicated that MNPs possessed good serum stability and well blood compatibility. In vitro, MNPs could be taken up by C6 cell in a concentration- and time-dependent manner with endosomes involved. In conclusion, MNPs were prepared using a simple one-step method with unique optical and good biological properties and could be used for bioimaging.

This study discusses the unbalanced development of Chinese inter-provincial high-grade highway from 1997 to 2013. It does so from the viewpoint of the inter-provincial Gini coefficient based on per capita mileage of high-grade highway, which is decomposed according to such dimensions as the increment of the Gini coefficient, the Gini coefficient of different types of high-grade highway, and the Gini coefficient between and within inland and coastal areas. The Gini coefficient of China’s per capita mileage of inter-provincial high-grade highway shows a declining trend year by year. According to the results from the decomposition of the contribution rate of different types of high-grade highway, the unbalanced development of inter-provincial high-grade highway is caused mainly by that of first- and second-grade highway. According to the results from the decomposition related to the increment of the Gini coefficient of China’s per capita mileage of inter-provincial high-grade highway, the decrease of the Gini coefficient from 1997 to 2013 was mainly the result of balanced distribution of high-grade highway among regions in China. According to the results from the decomposition of the Gini coefficient between and within inland and coastal areas, the unbalanced development of inter-provincial high-grade highway in China from 1997 to 2013 was caused mainly by the unbalanced development of inter-provincial high-grade highway in inland areas. Therefore, the authors argue that the government should pay more attention to protecting the environment and providing a suitable scale of highway network, which could promote long-term sustainable development.

Although development of nanomedicines has been a promising direction in tumor treatment, the therapeutic outcome of current nanomedicines is unsatisfying, partly because of the poor retention and penetration in tumors. Recently, a kind of tumor microenvironment sensitive size shrinkable nanoparticles (DOX-AuNPs-GNPs) has been developed by our lab, which could enhance the tumor penetration and retention depending on the size shrinking. However, the further enhancement is still restricted by dense collagen network in tumors. Thus in this study, we combined DOX-AuNPs-GNPs with losartan to deplete tumor collagen (constituted up to 90% of extracellular matrix) to further improve tumor penetration. In vitro, DOX-AuNPs-GNPs can shrink from over 117.8 nm to less than 50.0 nm and release DOX-AuNPs under the triggering of tumor overexpressed matrix metalloproteinases-2 (MMP-2). In vivo, pretreatment with losartan significantly decrease the collagen level and improve the tumor penetration. In combination, losartan combined with DOX-AuNPs-GNPs showed the best drug delivery efficiency, striking penetration efficiency and best 4T1 breast tumor inhibition effect. In conclusion, this study provided a promising synergetic strategy to improve the tumor treatment efficiency of nanomedicines. Statement of significance We have developed a dual strategy for deep tumor penetration through combining size shrinkable DOX-AuNPs-GNPs with depleting tumor collagen by losartan. Additionally, we demonstrate therapeutic efficacy in breast tumor bearing mouse model. DOX-AuNPs-GNPs co-administration with losartan is a novel and highly attractive strategy for anti-tumor drug delivery with the potential for broad applications in clinic.

Glioma is still hard to be treated due to their complex microenvironment. In this study, a gold nanoparticle-based delivery system was developed. The system, An-PEG-DOX-AuNPs, was loaded with doxorubicin (DOX) through hydrazone, an acid-responsive linker, and was functionalized with angiopep-2, a specific ligand of low density lipoprotein receptor-related protein-1 (LRP1), which could mediate the system to penetrate blood brain barrier and target to glioma cells. The particle size of An-PEG-DOX-AuNPs was 39.9 nm with a zeta potential of -19.3 mV, while the DOX loading capacity was 9.7%. In vitro, the release of DOX from DOX-AuNPs was pH-dependent. At lower pH values, especially 5.0 and 6.0, release of DOX was much quicker than that at pH 6.8 and 7.4. After coating with PEG, the acid-responsive release of DOX from PEG-DOX-AuNPs was almost the same as that from DOX-AuNPs. Cellular uptake study showed obviously higher intensity of intracellular An-PEG-DOX-AuNPs compared with PEG-DOX-AuNPs. In vivo, An-PEG-DOX-AuNPs could distribute into glioma at a higher intensity than that of PEG-DOX-AuNPs and free DOX. Correspondingly, glioma-bearing mice treated with An-PEG-DOX-AuNPs displayed the longest median survival time, which was 2.89-fold longer than that of saline. In conclusion, An-PEG-DOX-AuNPs could specifically deliver and release DOX in glioma and significantly expand the median survival time of glioma-bearing mice.