Biocompatible CuS-based nanoplatforms for multifunctional theranostics

Written by Dr Sudip Mukherjee

The rationale for combination therapy is to employ various therapeutic methods which work using different mechanisms, thereby decreasing the chance of developing resistant cancer cells. Photothermal therapy (PTT) is the use of electromagnetic radiation to eradicate cancer cells which can also be utilized to increase the effectiveness of chemotherapy or radiation therapy. The application of targeted and functional nanoparticles can be used to overcome the existing limitations of nonspecific toxicity which is associated with PTT. Therefore, functional nanomaterials with near-infrared (NIR) PTT, high biocompatibility and excellent photothermal conversion efficiency can be dynamic tools for cancer ablation without affecting normal healthy tissue.
Biocompatible CuS-based nanoplatforms for multifunctional theranostics

The Chen group used core-shell water-soluble copper sulphide nanoparticles (CuSNPs) coated with mesoporous silica nanoshells (MSNs) for effective delivery of anti-cancer drug doxorubicin (DOX) towards H22 liver cancer. Cleverly, the hollow cavity of MSN was utilized for the loading of anti-cancer drug DOX. CuS@MSN-DOX demonstrated good water dispersibility, high stability, excellent biocompatibility and strong NIR absorption. Its excellent photothermal and NIR thermal imaging properties are due its strong NIR photothermal conversion efficiency. The anti-tumor activity of CuS@MSN-DOX was extensively studied in both in vitro and in vivo therapeutic models which supports excellent chemotherapeutic activity. Complete eradication of the liver tumor was observed by combination therapy of PTT and chemotherapy using CuS@MSN-DOX. Infrared thermal imaging was used to monitor the photothermal treatment. These results clinically validate the multifunctional cancer theranostics property of CuS@MSN-DOX that has enormous potential for clinically translatable thermochemotherapy and enhanced drug delivery in the future.

 

Biocompatible CuS-based nanoplatforms for efficient photothermal therapy and chemotherapy in vivo Biomater. Sci., 2017, 5, 475 – 484

 

 

About the WebwriterDr. Sudip Mukherjee

Dr. Sudip Mukherjee is a Web Writer for Biomaterials Science. He is currently a Postdoctoral Research Associate working alongside Dr. Omid Veiseh at the Department of Bioengineering at the Rice University. His research is involved in the development of advanced nanomaterials for drug/gene delivery in cancer theranostics, immunomodulatory applications & angiogenesis. He published a total of ~30 research articles/patents. He serves as International Advisory Board Member for‘Materials Research Express‘, IOP Sciences. He is an associate member (AMRSC) of RSC, UK. He serves as reviewer for several international journals like Chem Comm, J Mater Chem A, J Mater Chem B, Journal of Biomedical Nanotechnology, RSC Advances, IOP Nanotechnology etc.
Contact Email: sudip.mukherjee@rice.edu

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Focus on: Nanoparticle Delivery Systems

Written by web writer Yingfei Xue

Developing nanoparticle formulations that can deliver drugs more effectively to the target sites with enhanced efficacy and reduced side effects has been an overarching goal in the field of nanobiotechnology. Dendrimers, micelles, and liposomes represent three major classes of nanoparticles that have shown promising results in drug delivery and bio-sensing.  Each type of nanoparticle has its own strengths and limitations in terms of the desirable payload, site of action, duration of action, release profile, and dosing frequency. Therefore, it is imperative to engineer these classical nanoparticle delivery systems for specific drug delivery application.

Nanoparticle delivery system

This month we focus on four articles published in Biomaterials Science reporting the recent advances in leveraging those different nanoparticle delivery systems for efficient, controlled, and targeted delivery of therapeutic agents.

1. Nucleobase-modified polyamidoamine-mediated miR-23b delivery to inhibit the proliferation and migration of lung cancer
Haobo Han, Jiebing Yang, Yudi Wang, Wenqi Chen, Jiawen Chen, Yan Yang and Quanshun Li
Biomater. Sci., 2017, 5, 2268. DOI: 10.1039/c7bm00599g

In the current study, the authors aimed to further improve the transfection efficiency and biocompatibility of conventional polyamidoamine (PAMAM) dendrimers. To this end, the surface of PAMAM was chemically modified with 2-amino-6-chloropurine. This modification further enhanced the carrier/DNA interaction via the fine balance of hydrogen bonding and electrostatic interaction. Compared to the prototype PAMAM, the modified PAMAM demonstrated higher transfection efficiency. In an in vitro model, this gene carrier delivered miR-23b, a potent anti-proliferative and anti-invasive agent, more efficiently into A549 cancer cells, indicating the potential of this carrier in cancer nanotherapy.

2. Novel poly(vinyl alcohol)-based amphiphilic nanogels by non-covalent boric acid crosslinking of polymeric micelles
Hen Moshe, Yuval Davizon, Maya Menaker Raskin and Alejandro Sosnik
Biomater. Sci., 2017, 5, 2295. DOI: 10.1039/c7bm00675f

Poor physical stability often presents as a major drawback for polymeric micelles. The authors addressed this issue by non-covalent crosslinking of a poly(vinyl alcohol) (PVA) based polymeric micelles system with boric acid. Compared to the non-crosslinked control, this novel micelles demonstrated improved physical stability under harsh environment. More interestingly, these micelles could be spray-dried and efficiently consolidated into dry powders which were able to regenerate back into the original nanoparticles upon re-dispersion. This non-covalently crosslinked micelles also maintained good mucoadhesiveness and cytocompatibility.

3. Codelivery of sorafenib and GPC3 siRNA with PEI-modified liposomes for hepatoma therapy
Weitong Sun, Yong Wang, Mingyue Cai, Liteng Lin, Xiaoyan Chen, Zhong Cao, Kangshun Zhu and Xintao Shuai
Biomater. Sci., 2017, 5, 2468. DOI: 10.1039/c7bm00866j

Combination therapy using chemotherapeutic drugs and siRNA represents a promising strategy that can potentially induce and/or enhance the synergistic anticancer effects. To overcome the individual drawbacks of sorafenib and gene therapy, the authors developed a PEI based liposome system which allow the co-delivery of GPC3 siRNA and hydrophobic sorafenib molecule. The drug loaded liposomal delivery system displayed enhanced anticancer effects by suppressing the expression of the anti-apoptotic GPC3 gene and the proliferative cyclin D1 gene simultaneously in human hepatocellular carcinoma (HCC) HepG2 cells. Further, the improved therapeutic effects of this delivery system was demonstrated in an in vivo xenograft model.

4. Dimeric camptothecin-loaded RGD-modified targeted cationic polypeptide-based micelles with high drug loading capacity and redox-responsive drug release capability
Zhaopei Guo, Xingzhi Zhou, Mengze Xu, Huayu Tian, Xuesi Chen and Meiwan Chen
Biomater. Sci., 2017, 5, 2501. DOI: 10.1039/c7bm00791d

To tackle the low bioavailability problem of camptothecin, the authors devised a novel polymeric micelles system composed of cationic polypeptide poly-lysine-block-poly-leucine, polyethylene glycol (PEG), and arginine-glycine-aspartic acid (RGD) peptide. The micelles system increased drug encapsulation efficiency, drug loading capacity, and physical stability of camptothecin. The RGD moiety further enhanced the intracellular uptake of micelles due to the cellular targeting capability of RGD sequence. Importantly, the drug loaded micelles effectively inhibited the proliferation of malignant MDA-MB-231 breast cancer cells by inducing cellular apoptosis and decreasing mitochondrial membrane potential.

Read these articles for free until 10 January 2018

About the webwriterYingfei Xue

Yingfei Xue is a web writer for Biomaterials Science. Currently, he is a PhD candidate and graduate student researcher in Dr. Shilpa Sant lab at the University of Pittsburgh, USA.  His research focus on nano-/micro-technology in novel heart valve therapy. Find him on Twitter: @Phil_Xue or connect with him on ResearchGate

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2018 Biomaterials Science Lectureship is now open for nominations!

Do you know an early-career researcher who deserves recognition for their contribution to the biomaterials field?

Now is your chance to put them forward for the accolade they deserve.

Biomaterials Science is pleased to announce that nominations are now being accepted for its 2018 Lectureship award. This annual award was established in 2014 to honour an early-stage career scientist who has made a significant contribution to the biomaterials field.

2017 winner Zhuang Liu receives his certificate from Executive Editor Neil Hammond

Previous winners

2017 – Zhuang Liu, Soochow University, China

2016 – Fan Yang, Stanford University, USA

2015 – Joel Collier, Duke University, USA

2014 – Suzie Pun, University of Washington, USA

Qualification

To be eligible for the Biomaterials Science Lectureship, the candidate should be in the earlier stages of their scientific career, typically within 7 years of attaining their first independent research position, and will have made a significant contribution to the field.

Description

The recipient of the award will be asked to present a lecture at the European Society for Biomaterials Annual Meeting in Maastricht in September 2018, where they will also be presented with the award. The Biomaterials Science Editorial Office will provide financial support to the recipient for travel and accommodation costs.

The recipient will also be asked to contribute a lead article to the journal and will have their work showcased free of charge on the front cover of the issue in which their article is published.

Selection

The recipient of the award will be selected and endorsed by the Biomaterials Science Editorial Board.

Nominations

Those wishing to make a nomination should send details of the nominee, including a brief C.V. and a letter supporting the nomination, to the Biomaterials Science Editorial Office by 28th February 2018. Self-nomination is not permitted.

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Congratulations to Biomaterials Science Award Winners at ICBZM2017

The 3rd International Conference on Bioinspired and Zwitterionic Materials

Biomaterials Science was proud to sponsor ICBZM2017, which took place this year in Tokyo, from the 18th to the 20th October. During the conference two Biomaterials Science Poster prizes were awarded.

Winners of the Biomaterials Science poster prize were;

Sarah Ward, (University of Massachusetts), for her poster presentation on ‘Polymer Zwitterion Prodrugs as Chemotherapeutics’.

Sarah Ward

Sarah Ward with Professor Todd Emrick

Erik Liu, (University of Washington), for his poster presentation on ‘Expression of EK Fusion Proteins to Enhance Protein Kinetics and Stability’.

Erik Liu

Erik Liu with Professor Shaoyi Jiang

 

Congratulations to both Sarah and Erik!

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Repurposing Drug Action with Targeted Nanomedicine

Written by Dr. Sudip Mukherjee

In cancers, rapid tumour growth is attributed to overexpression of anti-apoptotic proteins, inhibition or functional inefficiency of apoptotic proteases like caspases. Among caspases, caspase-8 signalling cascade is vital and interesting because of its ability to induce cell death by involving both mitochondria mediated intrinsic as well as death receptor (DR) – mediated extrinsic pathways. Notably, among ovarian cancer patients, tumors with low levels of caspase 8 are inherently resistant to chemotherapies. Incidentally, aggressive melanoma cells have functional expression of both Folate receptor (FR) on cell membrane and Estrogen receptor (ER) in cytoplasm. Stitching these basic facts one can deliver anti-cancer drugs, possibly targeting ER, using a liposomal system which will carry FR-targeting ligand to treat the aggressive melanoma cells.

In this present work, the Banerjee group used a hydrophobic drug molecule called NME2 (a recently developed ER-targeted anticancer drug for the treatment in breast cancer). Using a special FR-targeted liposome, the drug was successfully delivered to FR-moderately expressing melanoma cells.

Melanoma Regression in Mice

The efficient targeting to FR-moderately expressed melanoma cells was accomplished by a new robust, cationic folate ligand named FA8. This efficiency of delivery is in stark contrast to other available FR-targeted liposomes which target only FR-over expressing cancer cells. The concoction of NME2 in FA8-associated liposome selectively induced caspase-8 expression-mediated apoptotic cell death in melanoma cancer cells (in vitro and in vivo). However, the drug in pristine state or in non-targeted liposome could not induce caspase-8 mediated apoptosis. Preliminarily, docetaxel, another potent anticancer drug, showed a similar result upon FA8-mediated delivery. Clearly, the given FR-targeted, liposomal delivery methodology indicated a change in mechanism of anticancer action of drug cargo and hence exemplified an interesting possibility to elude impending drug resistance (if any) against the given drug.

Tips from the authors:

1) In MDR cancers repurposing drug’s mechanistic pathway is essential, as acquired drug resistance is one of the major obstacles in fruitful cancer treatment.

2) The given FR-targeted formulation affected the change of mechanism of action of drug cargo (here, NME2) from non-caspase 8 to caspase-8 mediated apoptosis, thereby repurposing the apoptotic pathway of encapsulated drug.

3) The unique cationic lipid-conjugated folic acid based-ligand facilitated a) targeting to FR-moderately expressed melanoma cells; b) modification of mechanistic action of drug-cargo.

4) The liposomal delivery system with an FR-targeting ligand instigated an independent cell death pathway through the up-regulation of caspase-8 with subsequent cleavage of pro-survival factor RIP-1.

Article Link:

Cationic folate-mediated liposomal delivery of bis-arylidene oxindole induces efficient melanoma tumor regression Biomater. Sci., 2017, 5, 1898-1909

About the Webwriter:

Dr. Sudip Mukherjee Dr. Sudip Mukherjee is a Webwriter for Biomaterials Science. He is currently a Postdoctoral Research Associate working alongside Dr. Omid Veiseh at the Department of Bioengineering at the Rice University. His research is involved in the development of advanced nanomaterials for drug/gene delivery in cancer theranostics, immunomodulatory applications & angiogenesis. He published a total of ~30 research articles/patents. He serves as International Advisory Board Member for ‘Materials Research Express‘, IOP Sciences. He is an associate member (AMRSC) of The Royal Society of Chemistry, UK. He serves as reviewer for several international journals like Chem Comm, J Mater Chem A, J Mater Chem B, Journal of Biomedical Nanotechnology, RSC Advances, IOP Nanotechnology etc.

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Mapping Oxygen Gradients in 3D Cell Cultures

Written by Dr. Sudip Mukherjee

Microenvironmental oxygen levels and gradients within three-dimensional (3D) tissue cultures directly influence cellular behavior and function, dictating the mode of proliferation, metabolism and interaction of cells with each other and their environment. While advances and prevalence of in vitro generated 3D cultures have spurred new techniques and systems for biological interrogation, it is necessary to develop and implement parallel systems to monitor and characterize the oxygen microenvironment within the tissue cultures and around them in the vessel used for the cultures. Conventional oxygen evaluation platforms can be ill-suited for continuous oxygen evaluation in custom tissue cultures. The Takayama group was able to robustly evaluate multiple 3D culture platforms by combining the use of phase-fluorimetry and lab-fabricated dispersible oxygen responsive microparticles. Oxygen microsensors were used to evaluate two spheroid culture vessels, hanging-drop and low-adhesion microwell plates, to highlight the variations in the oxygen levels peripheral to the spheroids in the two culture techniques. Dramatic differences can be seen in the steady state oxygen levels between the two culture techniques because of the difference in distance between the spheroids and the air-liquid interface in these two vessel types. These results highlighted the importance of minding the gas exchange location as compared to the cell culture to ensure appropriate tissue culture microenvironments.

Figure 1

Furthermore, these microsensors were used to map radial oxygen distribution across a circular, cell-patterned hydrogel by dispersing the microsensors within the culture. Coupling the spatial oxygen mapping to computational models of oxygen diffusion, the authors were able to estimate oxygen uptake behavior of the tissue culture. While 3D tissue culture platforms leverage the in vitro tissue architecture to produce more physiologically similar phenomena, integrated design and analysis of these 3D cell cultures from both biomaterial and oxygen supply aspects will be paramount in enabling researchers to effectively recreate some of the complexities present within both healthy and diseased tissues.

Tips from the authors:

  1. When fabricating oxygen microsensing beads, infusion with Dichloromethane enabled large amount of Ruthenium caging within the PDMS microspheres, while leaving them oxygen sensitive. While other solvents swell PDMS more readily and enabled higher efficiency infusion of ruthenium, these solvents resulted in oxygen unresponsive ruthenium loaded PDMS beads.
  2. Microsensors cannot be effectively integrated in the multicellular spheroids we tried with HEK293T, HS-5 and MDA-MB-231 cells; as the spheroids contract microsensors are ejected out of the spheroids.
  3. The only limitation of phase-fluorimetry for the oxygen measurements is sufficient signal output that it can be detected by the photodiode, or other detection system. This was generally not a problem with beads greater than 80 microns assuming the culture systems was less than 1-mm thick. However, we were unable to effectively infuse beads under 80 microns with enough ruthenium to have enough output signals from the microsensors to get robust readings with cultures > 1 mm.

Article Link:

Dispersible oxygen microsensors map oxygen gradients in three-dimensional cell cultures Biomater. Sci., 2017,5, 2106-2113

About the WDr. Sudip Mukherjee ebwriter:

Dr. Sudip Mukherjee is a Web Writer for Biomaterials Science. He is currently a Postdoctoral Research Associate working alongside Dr. Omid Veiseh at the Department of Bioengineering at the Rice University. His research is involved in the development of advanced nanomaterials for drug/gene delivery in cancer theranostics, immunomodulatory applications & angiogenesis. He published a total of ~30 research articles/patents. He serves as International Advisory Board Member for ‘Materials Research Express’, IOP Sciences. He is an associate member (AMRSC) of RSC, UK. He serves as reviewer for several international journals like Chem Comm, J Mater Chem A, J Mater Chem B, Journal of Biomedical Nanotechnology, RSC Advances, IOP Nanotechnology etc.

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Brazil MRS Meeting – New frontiers on biomaterials for bone regeneration

Biomaterials Science is pleased to support the ‘New frontiers on biomaterials for bone regeneration‘ symposium at the 2017 Brazil MRS Meeting, which will take place from 10-14 September in Gramado, Brazil.

The focus of this symposium is on advanced biomaterials for bone regeneration, including biomimetic materials or emerging metallic alloys, ceramics, natural and synthetic polymers, composites, and adhesives, as well as their interactions with proteins, blood, cells and mineral tissues.

By gathering together clinicians, biologists, materials researchers, engineers and industrials, this symposium will highlight the most recent advances on biomaterials for bone regeneration.

Confirmed invited speakers:

Register to attend now – click here to access the registration page or visit the website for more information.

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ACS Polymeric Materials: Science and Engineering Symposium 2017

 

Biomaterials Science is proud to sponsor the PMSE Symposium: Synthesis, Self-Assembly & Applications of Peptides & Polypeptides, at this year’s ACS Fall meeting.

The conference, which will take place from 20-24 August in Washington, DC, offers scientific professionals a legitimate platform to present, publish, discuss and exhibit the most exciting research discoveries and technologies in chemistry and its related disciplines, as well as providing them a greater understanding of the role chemistry plays in the global economy, health, safety, and the environment.

The PMSE Symposium, held on Sunday 20 August and organised by Jianjun Cheng and Hua Lu, will cover topics such as:

  • Design and self-assembly of polypeptide and elastin-like amphiphilic copolymers
  • Development of polypeptide hydrogels for central nervous system therapy
  • Scaffold directed cooperative polymerization of amino acid N-carboxyanhydrides
  • Versatile star-shaped polypeptide conjugates with controlled self-assembly as therapeutics

Registration is now open – click here to register now and take a look at the programme overview.

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IMRC 2017 – Biomaterials for Tissue Regeneration

We are pleased to announce the Biomaterials for Tissue Regeneration symposium which will take place at the 25th International Materials Research Congress in Cancun, Mexico.

The symposium, endorsed by Biomaterials Science and held from 20-25 August, will gather together clinicians, biologists, materials researchers, engineers and industrialists to highlight the most recent advances on the interactions of biomaterials with cells and tissues.

The focus of the symposium is on the most novel knowledge on the cross-talking between biomaterials and biological systems, i.e how biomaterials, including biomimetic materials or emerging metallic alloys, ceramics, natural and synthetic polymers, composites, and adhesives, interact with proteins, blood, cells and mineral tissues in order to provide tissue regeneration.

Confirmed invited speakers:

Early bird registration ends on 31 May – click here to register now or visit the IMRC website for more information.

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2017 Biomaterials Science Lectureship awarded to Zhuang Liu

It is with great pleasure that we announce Prof. Zhuang Liu (Soochow University, China) as the recipient of the 2017 Biomaterials Science Lectureship.

The Biomaterials Science Lectureship is an annual award that honours an early-career researcher for their significant contribution to the biomaterials field. The recipient is selected by the Biomaterials Science Editorial Board from a list of candidates nominated by the community.

Read on to find out more about Zhuang…

Prof. Zhuang Liu

 

Zhuang Liu obtained his PhD in Chemistry at Stanford University in 2008 after completing a Bachelor’s Degree at Peking University in 2004. He remained another year at Stanford University for a postdoctoral fellowship, before becoming a Professor at the Institute of Functional Nano & Soft Material (FUNSOM), in Soochow University, China in 2009.

His current research interests focus on the development of various synthetic functional nanomaterials as well as natural biomaterials for applications in biomedical imaging, drug delivery, and novel cancer therapies. Since 2005, Dr. Liu has authored over 255 peer-reviewed papers, which have been cited over 27,000 times. He was listed as one of the ‘Most Cited Chinese Researchers (Materials Science)’ by Elsevier in 2014 and 2015, and one of the ‘Highly Cited Researchers 2015 (Chemistry, Materials)’ by Thomson Reuters. He received the NSFC distinguished young scholar award in 2015.

 

 

 

 

To learn more about Zhuang’s research, have a look at his recent publication in Biomaterials Science:

Comparison of nanomedicine-based chemotherapy, photodynamic therapy and photothermal therapy using reduced graphene oxide for the model system
Jingjing Liu, Kai Liu, Liangzhu Feng, Zhuang Liu and Ligeng Xu
Biomater. Sci.
, 2017, 5, 331-340

 

We would like to thank everybody who nominated a candidate for the Lectureship; we received many excellent nominations, and the Editorial Board had a difficult task in choosing between some outstanding candidates.

Please join us in congratulating Zhuang on his award!

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