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Microbial enzymes are crucial catalysts in various industries due to their versatility and efficiency. The microbial enzymes market has recently expanded due to increased demand for many reasons. Among them are eco-friendly solutions, developing novel microbial strains with enhanced enzymes that perform under harsh conditions, providing sustainability, and raising awareness about the benefits of enzyme-based products. By 2030, the global enzyme market is expected to account for $525 billion, with a growth rate of 6.7 %. L-asparaginase and L-glutaminase are among the leading applied microbial enzymes in antitumor therapy, with a growing market share of 16.5 % and 9.5 %, respectively. The use of microbial enzymes has opened new opportunities to fight various tumors, including leukemia, lymphosarcoma, and breast cancer, which has increased their demand in the pharmaceutical and medicine sectors. Despite their promising applications, commercial use of microbial enzymes faces challenges such as short half-life, immunogenicity, toxicity, and other side effects. Therefore, this review explores the industrial production, purification, formulation, and commercial utilization of microbial enzymes, along with an overview of the global enzyme market. With ongoing discoveries of novel enzymes and their applications, enzyme technology offers promising avenues for cancer treatment and other therapeutic interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Liposomes serve as promising and versatile vehicles for drug delivery. Tracking these nanosized vesicles, particularly in vivo, is crucial for understanding their pharmacokinetics. This study introduces the design and synthesis of three new conjugated electrolyte (CE) molecules, which emit in the second near-infrared window (NIR-II), facilitating deeper tissue penetration. Additionally, these CEs, acting as biomimetics of lipid bilayers, demonstrate superior compatibility with lipid membranes compared to commonly used carbocyanine dyes like DiR. To counteract the aggregation-caused quenching effect, CEs employ a twisted backbone, as such their fluorescence intensities can effectively enhance after a fluorophore multimerization strategy. Notably, a "passive" method was employed to integrate CEs into liposomes during the liposome formation, and membrane incorporation efficiency was significantly promoted to nearly 100%. To validate the in vivo tracking capability, the CE-containing liposomes were functionalized with cyclic arginine-glycine-aspartic acid (cRGD) peptides, serving as tumor-targeting ligands. Clear fluorescent images visualizing tumor site in living mice were captured by collecting the NIR-II emission. Uniquely, these CEs exhibit additional emission peak in visible region, enabling in vitro subcellular analysis using routine confocal microscopy. These results underscore the potential of CEs as a new-generation of membrane-targeting probes to facilitate the liposome-based medicine research., (© 2024 Wiley-VCH GmbH.)

Biopolymers with excellent biocompatibility and biodegradability show great potential for designing drug nanocarriers, while it's difficult to fabricate smart vehicles with multiple switching (size, surface, shape) based on biopolymers alone. Here, we report a dual size/charge-switchable and multi-responsive doxorubicin-loaded gelatin-based nanocluster (DOX-icluster) for improved tumor penetration and targeted anti-tumor therapy. The DOX-icluster was electrostatically assembled from folic acid and dimethylmaleic anhydride modified gelatin (FA-GelDMA) and small-sized DOX-loaded NH 2 modified hollow mesoporous organosilicon nanoparticles (DOX-HMON-NH 2 ). DOX-icluster had an initial size of about 199 nm at neutral pH. After accumulation in tumor tissue, the DMA bond of FA-GelDMA was cleaved and gelatin was degraded by matrix metalloproteinase (MMP-2), thus 48 nm and positively charged DOX-HMON-NH 2 was released to facilitate penetration and cell internalization. DOX-HMON-NH 2 was further degraded by intracellular glutathione (GSH) with releasing 48.1 % of DOX. The cellular uptake results indicated that the fabricated icluster promoted the uptake of DOX by 4T1 cells. With enhanced penetration efficacy, the tumor spheroids volume treated with DOX-icluster was reduced to 15.1 % on day 7. This cytocompatible multi-responsive gelatin-based icluster with size-shrinking and charge-reversible characteristics may be used as a significant drug carrier for tumor therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In this paper, guaiacyl dehydrogenated lignin polymer (G-DHP) was synthesized using coniferin as a substrate in the presence of β-glucosidase and laccase. Carbon-13 nuclear magnetic resonance ( 13 C-NMR) determination revealed that the structure of G-DHP was relatively similar to that of ginkgo milled wood lignin (MWL), with both containing β-O-4, β-5, β-1, β-β, and 5-5 substructures. G-DHP fractions with different molecular weights were obtained by classification with different polar solvents. The bioactivity assay indicated that the ether-soluble fraction (DC 2 ) showed the strongest inhibition of A549 lung cancer cells, with an IC 50 of 181.46 ± 28.01 μg/mL. The DC 2 fraction was further purified using medium-pressure liquid chromatography. Anti-cancer analysis revealed that the D 4 and D 5 compounds from DC 2 had better anti-tumor activity, with IC 50 values of 61.54 ± 17.10 μg/mL and 28.61 ± 8.52 μg/mL, respectively. Heating electrospray ionization tandem mass spectrometry (HESI-MS) results showed that both the D 4 and D 5 were β-5-linked dimers of coniferyl aldehyde, and the 13 C-NMR and 1 H-NMR analyses confirmed the structure of the D 5 . Together, these results indicate that the presence of an aldehyde group on the side chain of the phenylpropane unit of G-DHP enhances its anticancer activity.

Cancer immunity is dependent on dynamic interactions between T cells and dendritic cells (DCs). Polymer-based nanoparticles target DC receptors to improve anticancer immune responses. In this paper, DC surface receptors and their specific coupling natural ligands and antibodies are reviewed and compared. Moreover, reaction mechanisms are described, and the synergistic effects of immune adjuvants are demonstrated. Also, extracellular-targeting antigen-delivery strategies and intracellular stimulus responses are reviewed to promote the rational design of polymer delivery systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Reactivity of MCEC (3) with diazonium chloride, DMF-DMA and NH 2 NH 2 to afford fused heterocyclic cellulosic derivative which confirmed through spectral analysis. Also, the cellulosic compounds were evaluated their growth inhibitory activity contra cancer cells A549 and Caco2 using neutral red uptake assay. Compounds, MCEN(6), MCPT(5a), MCPT(5b) showed better growth inhibitory activity on A549 and Caco2 growth compared to control values. While compound MCPY(7) exerted the best cytotoxic activity against A549 cells after 48 h. The expression levels of HIF-1α, β-Catenin, MYC, Cyclin D1 and MMP7 genes in A549 cells were examined using QRT-PCR. The compounds MCEN(6) and MCPY(7) down regulated levels of β-Catenin, MYC, Cyclin D1 and MMP7 genes and up-regulated levels of HIF-1α when treated with A549 cells compared to control values. Also, these biological studies confirmed through docking stimulation with different proteins and showed least binding energy with amino acids and attached with NH 2 and OH of cellulose with hydrogen bond interaction. Moreover, optimization of compounds using DFT/6-311(G) showed the stability of them and identifies their physical descriptors which showed excellent correlation with experimental results. Noteworthy, compounds, MCEN(6) and MCPY(7) were most promising anticancer agents against lung cancer through the regulation of apoptosis, cell cycle, proliferation, progression, chemo-resistance, and angiogenesis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Recent breakthroughs in the field of nanoparticle-based therapeutic delivery methods have changed the standpoint of cancer therapy by effectively delaying the process of disease development. Nanoparticles have a unique capacity of good penetrating ability than other therapeutic leads used in traditional therapeutics, and also, they have the highest impact on disease management. In the current study isolongifolene-loaded Chitosan nanoparticles have been formulated, synthesized and then characterized by the use of Fourier Transform Infrared Spectroscopy, X-ray Diffraction, Scanning Electron Microscopy and Transmission Electron Microscopy. Further, the characterized chitosan nano formulation was evaluated for hemocompatibility, plasma stability, and in-vitro release. Isolongifolene-loaded chitosan nanoparticles were found to be compatible with plasma and also, they exhibited a constant release pattern. Hence, chitosan-loaded nanoparticles could be employed as an excellent adjuvant in cancer therapeutic, to combat the multi-drug resistance in solid tumors., (© 2022. The Author(s).)

Although many treatments have been developed for oncotherapy, the lack of effective imaging guidance in the therapeutic process is still an urgent problem to be solved. In this study, magnetic resonance contrast agent (Gd) chelated on CuS nanoparticles and glucose oxidase (GOx) were coloaded into mesoporous silica nanoparticles (MSNs) to form GOx-Gd-CuS@MSNs, in which the Gd provided magnetic resonance imaging (MRI) for therapeutic process monitor while GOx could catalyze the generation of H 2 O 2 to enhance the photodynamic therapy (PDT). The in vitro results show that under near-infrared (NIR) laser irradiation (2 W·cm -2 , 5 min), temperature rapidly increased by approximately 30 °C for the accumulation of heat. At the same time, GOx on GOx-Gd-CuS@MSNs effectively consumed glucose to produce a large amount of H 2 O 2 , which was used to augment PDT through producing highly toxic hydroxyl radicals (·OH) and singlet oxygen ( 1 O 2 ). The photothermal and augmented-photodynamic could induce apoptosis and death of tumor cells. More importantly, the study found that GOx-Gd-CuS@MSNs had MRI performance, which provided imaging guidance during the treatment process, and it can monitor the diffusion of water molecules in the tumor tissue during the treatment and microcirculation perfusion of capillary network. These results indicate that the nanomaterial produced significant synergistic therapeutic effects through photothermal and photodynamic forces, meanwhile showed excellent spatial resolution and deep tissue penetration in imaging., (Copyright © 2022. Published by Elsevier Inc.)

Despite significant advances in early detection and personalized treatment, cancer is still among the leading causes of death globally. One of the possible anticancer approaches that is presently receiving a lot of attention is the development of nanocarriers capable of specific and efficient delivery of anticancer drugs. Graphene-based materials are promising nanocarriers in this respect, due to their high drug loading capacity and biocompatibility. In this review, we present an overview on the interactions of graphene-based materials with normal mammalian cells at the molecular level as well as cellular and subcellular levels, including plasma membrane, cytoskeleton, and membrane-bound organelles such as lysosomes, mitochondria, nucleus, endoplasmic reticulum, and peroxisome. In parallel, we assemble the knowledge about the interactions of graphene-based materials with cancerous cells, that are considered as the potential applications of these materials for cancer therapy including metastasis treatment, targeted drug delivery, and differentiation to non-cancer stem cells. We highlight the influence of key parameters, such as the size and surface chemistry of graphene-based materials that govern the efficiency of internalization and biocompatibility of these particles in vitro and in vivo. Finally, this review aims to correlate the key parameters of graphene-based nanomaterials specially graphene oxide, such as size and surface modifications, to their interactions with the cancerous and non-cancerous cells for designing and engineering them for bio-applications and especially for therapeutic purposes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Inorganic nanoparticles (INPs) have been paid great attention in the field of oncology in recent past years since they have enormous potential in drug delivery, gene delivery, photodynamic therapy (PDT), photothermal therapy (PTT), bio-imaging, driven motion, etc. To overcome the innate limitations of the conventional INPs, such as fast elimination by the immune system, low accumulation in tumor sites, and severe toxicity to the organism, great efforts have recently been made to modify naked INPs, facilitating their clinical application. Taking inspiration from nature, considerable researchers have exploited cell membrane-camouflaged INPs (CMCINPs) by coating various cell membranes onto INPs. CMCINPs naturally inherit the surface adhesive molecules, receptors, and functional proteins from the original cell membrane, making them versatile as the natural cells. In order to give a timely and representative review on this rapidly developing research subject, we highlighted recent advances in CMCINPs with superior unique merits of various INPs and natural cell membranes for cancer therapy applications. The opportunity and obstacles of CMCINPs for clinical translation were also discussed. The review is expected to assist researchers in better eliciting the effect of CMCINPs for the management of tumors and may catalyze breakthroughs in this area., (© 2022. The Author(s).)

Background: We have developed hybrid nanoparticles (NPs) by co-loading copper sulfide (CuS) NPs and glucose oxidase (GOD) (CuS@GOD NPs) to explore their antitumor properties., Purpose: To investigate the feasibility of using multiparametric magnetic resonance imaging (MRI) including intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and R 2 * mapping to quantitatively assess the early antitumor effect of CuS@GOD NPs., Study Type: Prospective., Animal Model: The orthotopic BALB/c mice 4 T1 breast cancer model. The 4 T1 xenografts in group 1 mice received normal saline, group 2 received CuS@GOD NPs, group 3 received CuS NPs plus laser, and group 4 received CuS@GOD NPs plus laser (n = 28 for each group)., Field Strength/sequence: A 3.0 T/IVIM-DWI MRI single-shot echo-planar imaging, R 2 * mapping spoiled gradient recalled echo (SPGR) sequence, T2-weighted images (T2WI) and T1-weighted images (T1WI) fast spin echo (FSE) sequence., Assessment: The IVIM-DWI and R 2 * mapping were performed before and after treatment at 0 hour, 0.5 hour, 1 hour, 2 hours, 4 hours, and 24 hours in four groups and the MRI parameters were obtained. Correlation analysis between the MRI parameters and histological analyses was conducted., Statistical Tests: One-way ANOVA, Pearson's correlation analysis, two independent samples t test, intraclass correlation coefficient. P < 0.05 was considered to be statistically significant., Results: In group 4, the tumoral D value was significantly higher than that of group 2 at 24 hours (0.541 ± 0.065 vs. 0.492 ± 0.051). The f value of group 4 was significantly lower than that of groups 1 and 2 at 2 hours (10.83 ± 2.16 vs. 14.28 ± 1.86, 16.67 ± 3.53, respectively). The R 2 * value was significantly increased at 0 hour in group 4 compared to that of groups 1 and 2 (64.552 ± 4.663 vs. 42.441 ± 1.516, 43.165 ± 1.709, respectively). D, f, and R 2 * were correlated with the histological staining results (r = 0.695-0.970)., Data Conclusion: The IVIM-DWI-derived D and f and R 2 * mapping-derived R 2 * could monitor early response to CuS@GOD NPs treatment in vivo., Evidence Level: 2 TECHNICAL EFFICACY: Stage 2., (© 2021 International Society for Magnetic Resonance in Medicine.)

Hydrogen peroxide (H 2 O 2 ) plays a vital role in organism due to its strong oxidizability, especially in resisting the invasion of pathogens. Cancer cells have abnormal concentrations of hydrogen peroxide due to their disordered reproduction. In complex biological systems, however, conventional fluorescent probes based solely on their fluorescent response to abnormal H 2 O 2 overexpression in cancer cells are not enough to distinguish cancer cells from other unhealthy or immune cells. Therefore, it is necessary to develop other methods to allow the probe to selectively enter the cancer cells and perform fluorescence imaging of the hydrogen peroxide in the cancer cells. Herein, we developed a biotin-guided, two-photon fluorescent probe (BT-HP) for sensitive detection of H 2 O 2 in cancer cells. Through the study on the properties of the probe, it was found that the probe can selectively enter cancer cells. The depth penetration imaging of H 2 O 2 in cancer cells and tumor tissues by two-photon microscope proves the potential of the probe BT-HP as a tumor targeting H 2 O 2 biosensor. The probe was further applied to detect hydrogen peroxide in cancer cells during the ferroptosis process., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Carbon dioxide (CO 2 ), an important gas molecule metabolite produced by the tricarboxylic acid cycle, is a direct signal for identifying cancers in cells and tissues. Herein, design and synthesis of a novel "breathable" block polymer supramolecular assembly probe consisting of a hydrophilic block, an amidine-containing CO 2 -responsive block, and an aggregation-induced emission (AIE) luminescence block to detect CO 2 metabolized by cancer cells is reported. The triblock copolymer poly-(4-undecoxy tetraphenyl ethylene methacrylate)- b -poly-(( N -amidino)-(2,3-dihydro-1 H -1, 4-methyl-1, 2,3-triazole)-(ethenylbenzene))- b -poly(ethylene oxide) (PTPE- b -PAD- b -PEO) was successfully synthesized and characterized. This triblock copolymer could be self-assembled into "breathable" aqueous solution vesicles. In the presence of CO 2 , the amidine-containing CO 2 -responsive block (PAD block) of the vesicle "inhales" an amount of CO 2 , which causes the volume of the vesicle to expand. The expansion of the vesicle induces the aggregation of the AIE luminescence block (PTPE block), which resulted in the fluorescence intensity enhancement. The supramolecular vesicles "exhale" CO 2 , and the volume and AIE phenomenon of the vesicles decrease when N 2 is passed into the solution. On the basis of this reversible change of fluorescence intensity, HeLa cervical cancer cells, CNE1 nasopharynx cancer cells, 5-8F nasopharynx cancer cells, 16HBE human bronchial epithelial cells, and GES-1 human gastric mucosa epithelial cells have all been successfully detected and identified.

The aim of the current study was to biosynthesize the silver nanoparticles (AgNPs) from the bacterial strain of Bacillus cereus (ATCC 14579) extracellularly. When bacterial extract was challenged with 1 mM silver nitrate (AgNO3) the color of the extract changed into brown confirms the formation of nanoparticles. These nanoparticles were capped with bovine serum albumin (BSA). UV- visible spectroscopy showed the absorption peak at 420 nm indicates the formation of AgNPs. Fourier Infra -red (FTIR) attenuated total reflection (ATR) spectroscopy showed amide and amine group associated with AgNPs that stabilizes the nanoparticles. Energy dispersive x-ray spectroscopy (EDX) showed a strong peak of silver confirms the presence of silver. Thermo gravimetric analysis (TGA) analysis was used to determine the protein degradation showed less protein degradation at higher temperature confirms the stability of nanoparticles. Transmission electron microscopy (TEM) showed the AgNPs are well dispersed and spherical, and 5.37 nm to 17.19 whereas albumin coated nanoparticles are size ranges from 11.26 nm to 23.85 nm. The anticancer effect of capped AgNPs (cAgNPs) showed the IC50 value against breast cancer MCF-7 at 80 μg/mL, intestinal colon cancer HCT- 116 60 μg/mL, and bone cancer osteosarcoma MG-63 cell line80 μg/mL while against normal fibroblast cells 3T3 cells showed the IC50 value at 140 μg/mL. Lactate dehydrogenase assay (LDH) showed higher toxicity on MCF-7, HCT-116, and MG-63 cells. The apoptotic study clearly showed the blebbing of membrane, chromatin condensation due to the production of reactive oxygen species (ROS) by ethidium bromide and acridine orange dual staining method. The DNA analysis showed the complete fragmentation of the DNA of treated cells when compared with control cells., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In ultrasonography, ultrasound contrast agents (UCAs) that possess high acoustic impedance mismatch with the bulk medium are frequently employed to highlight the borders between tissues by enhanced ultrasound scattering in a clinic. Typically, the most common UCA, microbubble, is generally close in size to a red blood cell (<∼10 μm). These microscale UCAs cannot be directly entrapped into the target cells but generate several orders of magnitude stronger echo signals than the nanoscale ones. And their large containment and high ultrasound responsiveness also greatly facilitate to perform combined treatments, e.g., drug delivery and other imaging techniques. So multifunctionalized microscale UCAs appear on this scene and keep growing toward a promising direction for precise theranostics. In this review, we systematically summarize the new advances in the principles and preparations of multifunctionalized microscale UCAs and their medical applications for malignant tumors.

Cancer has become one of the primary causes of death worldwide. Current cancer-therapy schemes are progressing relatively slowly in terms of reducing mortality, prolonging survival, time and enhancing cure rate, owing to the enormous obstacles of cancer pathophysiology. Therefore, specific diagnosis and therapy for malignant tumors are becoming more and more crucial and urgent, especially for early cancer diagnosis and cancer-targeted therapy. Derived theranostics that combine several functions into one "package" could further overcome undesirable differences in biodistribution and selectivity between distinct imaging and therapeutic agents. In this article, we discuss a chief clinical diagnosis tool - MRI - focusing on recent progress in magnetic agents or systems in multifunctional polymer nanoassemblies for combing cancer theranostics. We describe abundant polymeric MRI-contrast agents integrated with chemotherapy, gene therapy, thermotherapy, and radiotherapy, as well as other developing directions., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Tea polyphenols have received much attention from the pharmaceutical and food industries owing to their extraordinary antioxidant and antibacterial characteristics. However, tea polyphenols are very unstable in processing and storage, since they are sensitive to the environmental factors like temperature, light and pH. Therefore, the effective application of tea polyphenols requires a protective mechanism to maintain its activity. The utilization of compounded tea polyphenols, instead of raw materials, can potentially help to improve their stability. This review focuses on the summarization of the compounding technologies for tea polyphenols, including physical technologies, chemical-interfacial technologies and nano-scale compounding technologies. Of which, the emerging nano cellulose bio-carrier, as a promising technology, is particularly proposed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

As a key enzyme for glycolysis, lactate dehydrogenase (LDH) remains as a topic of great interest in cancer study. Though a number of kinetic models have been applied to describe the dynamic behavior of LDH, few can reflect its actual mechanism, making it difficult to explain the observed substrate and competitor inhibitions at wide concentration ranges. A novel mechanistic kinetic model is developed based on the enzymatic processes and the interactive properties of LDH. Better kinetic simulation as well as new enzyme interactivity information and kinetic properties extracted from published articles via the novel model was presented. Case studies were presented to a comprehensive understanding of the effect of temperature, substrate, and inhibitor on LDH kinetic activities for promising application in cancer diagnosis, inhibitor evaluation, and adequate drug dosage prediction.

Inorganic nanoparticles, which can absorb and convert near infrared (NIR) light to heat to ablate cancer cells, have been widely investigated in photothermal therapy. However, the inherent poor solubility and acute systemic toxicity of these inorganic particles hinder their application in clinical practice. Polymeric nanocomposites materials containing both inorganic nanoparticles and polymers could be harnessed to achieve enhanced photothermal therapeutic effect as well as improved biocompatibility and multi-responsiveness. Synergistic chemo-photothermal efficacy towards cancer cells and tumor tissue can thus be realized through such multi-functional and multi-responsive polymeric nanocomposites. In this review, the recent developments in polymeric nanocomposites based on different types of inorganic nanoparticles (i.e. gold, carbon nanotube, graphene, and upconversion nanoparticles) for NIR-triggered cancer therapy are summarized., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Cellulose is an important environmentally-friendly renewable polymer on the earth. Cellulose has been widely used as feedstocks for the synthesis of biomaterials, biofuels and biochemicals. Recently, cellulose and cellulose derivatives have received intense attention in biomedical applications, such as tissue engineering, scaffold, artificial blood vessel, skin grafts, artificial skin, drug carrier, and chronic skin diseases, many of which are somehow related to cancer therapy. In this mini-review, we focus on the up-to-date development of cellulosebased nanocarriers used for cancer therapy. Various cellulose-based nanocarriers such as bacterial cellulose (BC), cellulose acetate, microcrystalline cellulose, carboxymethyl cellulose, cellulose nanocrystals, cellulose nanofibrills, etc, are reviewed in terms of being used in drug delivery systems for cancer treatment. Different strategies for the synthesis of cellulose-based nanocarriers are summarized. Special attention is paid on the structure and properties of cellulose-based drug carriers for cancer therapy via some representative examples. Finally, the problems and future developments of these promising polymeric nanocarriers are raised and proposed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Ultrasound contrast agents (UCA) represented by gas-filled microbubble, can provide simultaneous and co-localized enhancement on image contrast to help disease diagnosis by highlighting tissue borders. Nowadays, Some UCAs (e.g. Levovist®, Optison®, Definity®, and Sonovue®) are commercially available, and have been clinically utilized for enhanced ultrasonography in the US, Canada, Europe, Asia and so on. However, their large diameters (1~10 µm) mainly hinder more precise and deeper applications in the imaging of capillaryabundant organs or tissues (e.g. tumor), and undersized nanoscale UCAs also lack enough backscattering echo intensity to distinguish abnormal distribution of vessels. So novel shapes, structures and materials of nano-sized UCAs are constantly emerging for cancer ultrasonic imaging. Particularly, the cavitation effect of diagnostic ultrasound can accelerate effusion of loaded contents from UCAs, following cellular uptake. This will inevitably contribute to develop other potential applications of nano-sized UCAs towards cancer therapy and theranostics., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

A water-soluble, ratiometric fluorescent pH probe, L-SRhB, was synthesized via grafting spirolactam Rhodamine B (SRhB) to lignosulfonate (LS). As the ring-opening product of L-SRhB, FL-SRhB was also prepared. The pH-response experiment indicated that L-SRhB showed a rapid response to pH changes from 4.60 to 6.20 with a pK a of 5.35, which indicated that L-SRhB has the potential for pH detection of acidic organelle. In addition, the two probes were internalized successfully by living cells through the endocytosis pathway and could distinguish normal cells from cancer cells by different cell staining rates. In addition, L-SRhB showed obvious cytotoxicity to cancer cells, whereas it was nontoxic to normal cells in the same condition. L-SRhB might have potential in cancer therapy. L-SRhB might be a promising ratiometric fluorescent pH sensor and bioimaging dye for the recognition of cancer cells. The results also provided a new perspective to the high-value utilization of lignin.

In the present study the effect of process (homogenization speed) and formulation (polymer-alginate-concentration, surfactant concentration, drug amount, perfluorohexane volume fraction and co-surfactant inclusion) variables on particle size, entrapment efficiency, and drug release kinetics of doxorubicin-loaded alginate stabilized perfluorohexane nanodroplets were evaluated. Particle size and doxorubicin entrapment efficiency were highly affected by formulation and process variables. Increase in homogenization speed resulted in significant decrease in particle size and increase in entrapment efficiency. Polymer concentration and perfluorohexane amount both had similar effect on particle size. Particle size increased by an increase in the amount of both. Entrapment efficiency increased by increasing polymer concentration. In case of surfactant concentration and drug amount, particle size and entrapment efficiency had optimum values and an increase in concentration of both of them behind a certain limit resulted in increase in particle size and decrease in doxorubicin entrapment. In vitro release profile of doxorubicin was an apparently biphasic release process and 7%-13% of drug released after 24h incubation in PBS, pH=7.4, depending on the nanodroplets composition but ultrasound exposure for 10min resulted in triggered release of 85.95% of doxorubicin from optimal formulation (formulation E1 with 39.2nm diameter size and 92.2% entrapment efficiency)., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Tumors cannot be understood in isolation from their microenvironment. Tumor and stromal cells change phenotype based upon biochemical and biophysical inputs from their surroundings, even as they interact with and remodel the microenvironment. Cancer should be investigated as an adaptive, multicellular system in a dynamical microenvironment. Computational modeling offers the potential to detangle this complex system, but the modeling platform must ideally account for tumor heterogeneity, substrate and signaling factor biotransport, cell and tissue biophysics, tissue and vascular remodeling, microvascular and interstitial flow, and links between all these sub-systems. Such a platform should leverage high-throughput experimental data, while using open data standards for reproducibility. In this chapter, we review advances by our groups in these key areas, particularly in advanced models of tissue mechanics and interstitial flow, open source simulation software, high-throughput phenotypic screening, and multicellular data standards. In the future, we expect a transformation of computational cancer biology from individual groups modeling isolated parts of cancer, to coalitions of groups combining compatible tools to simulate the 3-D multicellular systems biology of cancer tissues.