H index 280, the first person in biological materials!

The editorial department of Curious Things and Nanoman has compiled the big names of biomaterials, the academicians of the American Academy of Sciences ("Academicians of the Academy of Sciences", "Academicians of Engineering", "Academicians of the Academy of Arts and Sciences"), and "Professor of David H. Koch Institute of MIT". "(The highest honor that MIT professor can get) Part of the research results of Professor Robert S. Langers group in 2020.
Professor Robert Langer is a well-known scholar in the field of global bioengineering, especially for his research on targeted drug delivery systems and tissue engineering. His laboratory at MIT is currently the largest biomedical engineering laboratory in the world ( No one, and no rebuttal is accepted), as the first major in the field of biomaterials, the research group has achieved first-class technology to make products, second-rate achievements in water CNS, and third-rate products to be published.



His research group has published more than 1,500 articles so far, and has more than 1,400 published and pending patents worldwide. Professor Langers patents have been licensed or sublicensed by more than 400 pharmaceutical, chemical, biotechnology and medical device companies. He is the most cited engineer in history, with H-index 280, with more than 322,000 citations.



The main research directions of Professor Robert S. Langers group are:

1. Microstructure analysis and mathematical model study of polymer release mechanism

2. Research the application of these systems, including the development of effective long-term delivery systems for insulin, anti-cancer drugs, growth factors, gene therapy agents and vaccines

3. Develop a controlled release system that can be triggered by magnetic, ultrasonic or enzymatic to increase the release rate

4. Synthesis of a new type of biodegradable polymer delivery system

5. Create new methods to deliver drugs such as proteins and genes across complex barriers such as the blood-brain barrier, intestines, lungs and skin

6. Research new methods of creating tissues and organs, including creating new polymer systems for tissue engineering

7. Stem cell research, including controlling growth and differentiation

8. Create new biomaterials with shape memory or surface switching characteristics

9. Angiogenesis inhibition


The following is a summary of some representative research results of Robert Langers research team in 2020 for everyone to learn and communicate. (Mainly the corresponding author, please correct me if you have any omissions)
The following pages are divided into three parts

1. Drug Delivery

2. Oral delivery

3. Technical optimization



1. Drug Delivery



1. Nature Reviews Drug Discovery: Engineering precision nanoparticles for drug delivery (click to view detailed interpretation)

At present, many scientists want to overcome the biological obstacles of NP through precision medicine and personalized medicine. Based on the new NP design based on patient data, the delivery and response of precision drug therapy can be greatly improved.


In view of this, Academician Robert Langer of the Massachusetts Institute of Technology, Academician Nicholas A. Peppas of the University of Texas at Austin and Michael J. Mitchell of the University of Pennsylvania and others have published a review of engineered precision nanoparticles for drug delivery on Nature Reviews Drug Discovery. They focus on advances in nanomedicine, which can promote the clinical transformation of precision medicines and improve patient response to treatment, focusing on the use of biomaterials and biomedical engineering innovations to overcome biological barriers and patient heterogeneity.




Mitchell, M.J., et al. Engineering precision nanoparticles for drug delivery. Nat Rev Drug Discov(2020).

https://doi.org/10.1038/s41573-020-0090-8



2. Science Translational Medicine: A good "prescription" and a magical medicine only need one injection, and the pulsed drug release can effectively treat tumors! (Click to view detailed interpretation)







In current clinical trials, the dosing regimen of STING agonists includes multiple intratumoral injections (for example, three injections over a period of 28 days, or a treatment cycle every 9 weeks, once a week), up to 2 Years to achieve the therapeutic effect. There are too many injections, and the patient does not comply. In addition, multiple intra-tumor injections limit the scope of STING agonist-based treatment methods to easily available tumor types, and there is a risk of destroying the tumor microenvironment (TME) and vascular network, which may promote the extravasation and metastasis of cancer cells .



MIT Academician Robert Langer, Daniel G. Anderson, and Ana Jaklenec have developed a multi-dose drug delivery platform by engineering PLGA into cubic particles. The platform can release a certain dose of STING agonist at different time intervals, so that a single injection or implantation of particles can provide a complete treatment process.









XueguangLu, et al., Engineered PLGA microparticles for long-term, pulsatile release of STING agonist for cancer immunotherapy. Science Translational Medicine 2020.

DOI: 10.1126/scitranslmed.aaz6606

https://stm.sciencemag.org/content/12/556/eaaz6606



3. Advanced Drug Delivery Reviews: Parallel evolution of polymer chemistry and immunology: the combination of mechanobiology and material design





Robert Langer et al. discussed clinically device-based and micro/nanoparticle-based materials, as well as the biological understanding of how the immune system interacts with these materials, how these different immune cells become targets and targets for drug delivery design. Variables, and new directions in polymer chemistry to solve these interactions, and further promote our progress in medical treatment.







Kaitlyn Sadtler, et al., Parallel evolution of polymer chemistry and immunology: Integrating mechanistic biology with materials design. Advanced Drug Delivery Reviews 2020.

https://doi.org/10.1016/j.addr.2020.06.021



4. Nano Lett: Polymer nanocomposite micro-actuator, used to release chemical substances on demand through high-frequency magnetic field excitation







In the fields of chemical and biomedical engineering, on-demand delivery of substances has proven to have various applications. The single pulse release curves of micro/nano particles with different shape factors have been shown previously. However, to obtain sustained release, a pulsed release profile is required. Here, Robert Langer and others from the Massachusetts Institute of Technology demonstrated the release profile of drug-loaded polymer magnetic nanocomposite microspheres.



By activating the micro-actuator with an AC magnetic field, a cumulative release of 61% can be achieved within five days. One of the main advantages of using magnetic stimulation is that the characteristics of the environment where the particles are located (such as transparency, density, and depth) do not affect performance. The working amplitude of the magnetic field used in this work is safe and does not interact with any non-metallic materials. The method can be applied to the fields of microchemistry, drug delivery, lab-on-a-chip, and microrobots for drug delivery.







Seyed M. Mirvakili, et al., Polymer Nanocomposite Microactuators for On-Demand Chemical Release via High-Frequency Magnetic Field Excitation. Nano Letters 2020 20 (7), 4816-4822

DOI: 10.1021/acs.nanolett.0c00648



5. ACS Nano: Tissue Targeted Delivery Scalpel: Opportunities and Challenges of CRISPR/Cas-based Live Genome Editing






CRISPR/Cas9-based genome editing has quickly become a powerful breakthrough technology that can be used in multiple environments for biomedical research and therapeutic development. Recent efforts to understand in vitro gene modification methods have led to a significant increase in the efficiency of in vitro genome editing. Since genome-corrected disease targets are usually located in specific organs, to realize the full potential of genomic drugs, it is necessary to directly deliver the CRISPR/Cas9 system targeting specific tissues and cells in the body.



At this point, Robert Langer and others at MIT focused on the progress of delivering CRISPR/Cas components into the body. Both viral and non-viral delivery systems are expected to perform gene editing in a variety of tissues through local injection and systemic injection. They described various viral vectors and synthetic non-viral materials for in vivo gene editing and applications in research and therapeutic models, and summarized the opportunities and progress of these two methods so far. The challenges of viral delivery will also be discussed, including overcoming limited packaging capabilities, immunogenicity associated with multiple administrations, the potential for off-target effects, and non-viral delivery, including efforts to improve efficacy and expand the use of non-viral vectors in extrahepatic tissues. Application and cancer. Looking ahead, other advances in the safety and efficiency of viral and non-viral delivery systems for tissue and cell type-specific gene editing will be required to achieve extensive clinical translation. It also provides a summary of current delivery systems for in vivo genome editing, organized by route of administration, and highlights direct opportunities for biomedical research and applications. In addition, the current challenges of delivering the CRISPR/Cas9 system in vivo are discussed to guide the development of future therapies.

Tuo Wei, et al., Delivery of Tissue-Targeted Scalpels: Opportunities and Challenges for In Vivo CRISPR/Cas-Based Genome Editing. ACS Nano 2020 14 (8), 9243-9262

DOI: 10.1021/acsnano.0c04707



In addition, there are some research results of Professor Robert Langer as a co-author:



















2. Oral materials



6. PNAS: Development of a long-acting direct-acting antiviral system for porcine hepatitis C virus







Direct-acting antiviral (DAA) therapy is very effective against hepatitis C virus (HCV). Despite this, the burden of chronic hepatitis C is still high, especially among those who have difficulty taking drugs every day. Therefore, a long-acting DAA delivery mode can expand the treatment of HCV.



MIT Daniel G. Anderson, Robert Langer and others have developed a long-acting DAA system (LA-DAAS), which can support the HCV-DAAS multi-gram drug library and provide control of these drugs within a few weeks freed. The preliminary safety and effectiveness of LA-DAAS are proved on the pig model. Expanding the scope of DAA delivery to patients and healthcare providers will further work to eliminate HCV infection on a global scale.







Malvika Verma, et al., Development of a long-acting direct-acting antiviral system for hepatitis C virus treatment in swine. PNAS 2020.

https://www.pnas.org/content/117/22/11987.short



7. Science Advances: Absorbable transient anchoring electronics for microstimulation and signal conduction







Ingestible electronic devices are capable of non-invasive assessment and pathological diagnosis of the gastrointestinal tract (GI), but they usually cannot interact therapeutically with the tissue wall. For this reason, academicians Giovanni Traverso and Robert Langer of the Massachusetts Institute of Technology have developed an oral electrical stimulation device, which is characterized by autonomously inserting a conductive hook probe into an isolated human tissue and an in vivo pig model. Fixed on the stomach.



The probe provides stimulation to the tissue through timed electrical pulses and can be used as a method for treating gastric motility disorders. To demonstrate the interaction with gastric muscle tissue, the researchers used electrical stimulation to induce acute muscle contractions. The pulse transmits the successful anchoring and detachment events of the probe to the device placed parenterally. The ability to anchor into and interact with target gastrointestinal tissues controlled by the enteric nervous system provides opportunities to treat a variety of related pathologies.

Alex Abramson, et al., Ingestible transiently anchoring electronics for microstimulation and conductive signaling. Science Advances 2020.

DOI: 10.1126/sciadv.aaz0127







3. Technical optimization



8. Nature Biomed. Eng.: Automated whole tissue culture system for screening oral pharmaceutical preparations








Monolayer cancer cell lines are widely used to simulate gastrointestinal absorption of drugs and oral drugs
Development. However, they usually cannot predict the absorption of the drug in the body. For this, academicians Giovanni Traverso and Robert Langer of the Massachusetts Institute of Technology and others reported on a robotic operating system that uses large pig gastrointestinal tissue explants. These explants maintain their function in culture for a long time. , In order to conduct high-throughput interrogation of the entire part of the gastrointestinal tract (thousands of samples per day).

Key points of this article:

1) Compared with the Caco-2 Transwell system (Spearmans correlation coefficients are 0.906 and 0.302, respectively), the automated culture system is more predictive of drug absorption in the human gastrointestinal tract.

2) By using a culture system to analyze the intestinal absorption of 2930 peptide drug oxytocin preparations, the researchers found an absorption enhancer that can make the bioavailability of oral oxytocin in pigs without destroying intestinal tissue cells Degree increased by 11.3 times. The robot-operated whole tissue culture system should help promote the development of oral drug preparations and may also help drug screening applications.



von Erlach, T., et al. Robotically handled whole-tissue culture system for the screening of oral drug formulations. Nat Biomed Eng (2020).

https://doi.org/10.1038/s41551-020-0545-6



9. Science Advances: Optimize the injectability of microparticle drug formulations (click to view in-depth interpretation)

Inspired by the challenge and inspiration of injecting particles (especially large particles), Ana Jaklenec and Robert Langer of the Massachusetts Institute of Technology and others systematically studied the delivery of particles through hypodermic needles. Researchers have now developed a computational model that can help them improve the injectability of such particles and prevent clogging. The model analyzes various factors, including particle size and shape, to determine the best design for injectability. Using this model, the percentage of particles that researchers can successfully inject increased sixfold. They now hope to use the model to develop and test microparticles that can be used to deliver cancer immunotherapy drugs, as well as other potential applications.







MortezaSarmadi, et al., Modeling, design, and machine learning-based framework for optimal injectability of microparticle-based drug formulations. ScienceAdvances 2020.

DOI: 10.1126/sciadv.abb6594

https://advances.sciencemag.org/content/6/28/eabb6594







In addition, the research group has some research results, which are not listed here due to space limitations. Interested readers can go to the research group website to learn by themselves.



Research group website: https://langerlab.mit.edu/