Precision medicine is the most popular concept in recent years. From diagnosis, treatment to prognosis, all aspects of medical care are looking for suitable ways to achieve precision medicine. Specific to the drug development process, precision treatment is not only reflected in the precise guidance of targeted drugs, but also the precise delivery of new biological agents. Nowadays, nano-materials based on nanomaterials are becoming the new darling of the pharmaceutical industry, affecting the original drug development model.
Nanomedicine: a drug based on nanoscale materials
Nanomedicine can be broadly defined as the application of nanoscale materials in improving human health. This includes the development of early medical diagnostic and prophylactic applications, improvements in the diagnosis, treatment and follow-up of many life-threatening diseases, including cancer, cardiovascular disease, diabetes, AIDS, Alzheimer’s disease, Parkinson’s disease and various Inflammation and infectious diseases.
Nanomaterials range in size from 1-100 nm to basic biomaterials such as DNA, but their surface area is greatly increased, and their applications range from drug and gene delivery to biomedical imaging.
The nano drug has the characteristics of small particle size, large specific surface area, high surface reactivity, many active centers, and strong adsorption capacity. The use of nanomaterials as a drug carrier can improve the absorption and utilization of drugs, achieve efficient target delivery, prolong drug consumption half-life, and reduce harmful side effects on normal tissues.
Development formulas for nano drug particles include polymer nanoparticles, micelles, liposomes, dendrimers, metal nanoparticles, solid lipid nanoparticles, and the like. In 1995, researchers published the first liposome-based nano drug, Doxorubicin, for the treatment of tumors. To date, about 50 nanoparticle-based drugs have been developed due to the rapid development of science.
The interaction of nanomedicine with the biological environment (levels of molecules, cells, organs, etc.) is based on a complex series of interactions between particles and biological media. Each biological environment is unique. The particle size, shape, arrangement, surface charge distribution and surface chemistry of nanoparticles are the key factors determining the efficiency of the reaction between nanomedicine and its surrounding media.
Nanomedicine is mainly affected by three factors: biodistribution characteristics, cellular uptake rate, and the mechanism by which tissue is eventually cleared. The size of the drug determines how it is removed by the body. Particles smaller than 10 nm in size are removed by the kidneys; particles larger than 10 nm are eliminated by the liver and mononuclear phagocytic system.
The BCC study said in its September report that sales of nanostructure applications in the life sciences (such as nanoparticles, nanospheres, nanocapsules and quantum dots) are expected to continue to grow over the next five years. The global market for life sciences nanostructure applications will reach $17.8 billion in 2019 and is expected to reach $33.8 billion by 2024, with a compound annual growth rate of 13.7% over the next five years.
Gold nanoparticles (GNPs): both drug-loaded and therapeutic
Nanocarriers have the ability to increase tumor tissue permeability and retention rate effects (EPR). In addition, nano-drugs have the following advantages: loading multiple drugs to play a combined therapeutic role of drugs; targeting specific drugs to tumor cells and tumor microenvironment; simultaneously visualizing tumor treatment effects based on novel imaging techniques; prolonging drug cycle time; controlling drugs Release; and optimize treatment options to improve patient compliance.
It is worth mentioning that many widely used traditional chemotherapeutic drugs (such as taxanes and doxorubicin) have strong side effects and cause a variety of tumors to produce resistant mutations, which brings about the treatment of tumors. new challenge. A number of existing studies have shown that nanomedicine has the potential to overcome the above problems.
A particularly active area of nanomedical research is the design of functionalized gold nanoparticles as a versatile agent for biomedical imaging and drug delivery. Nanogold is known for its strong optical activity at the visible to near infrared (NIR) wavelength and is actively investigating contrast agents for optical imaging modalities. In particular, the NIR spectrum between 750 and 1300 nm provides a “biological window” through the optical absorption of tissue, as hemoglobin, bio-pigment and water attenuate the remaining wavelengths.
A new wave of research on gold nanoparticles is partly due to new developments in the scalable synthesis of anistropic gold particles. For example, gold nanorods (GNRs) with lengths well below 100 nm can now be prepared, and their high efficiency NIR (visible to near infrared) absorption can greatly increase the range of medical optical performance modes, such as optical coherence tomography (OCT). ) and photoacoustic tomography (PAT).
However, gold nanoparticles are not only passive imaging agents and carriers: most of the photons they absorb are converted into heat, producing a strong photothermal effect. At high gold nanoparticle concentrations and high laser power, these photothermal effects can produce a milder, high-temperature form with lower power illumination, resulting in ablation of nearby cells and tissues, enhancing the therapeutic effect in a more subtle way. These effects have spurred new concepts in nanomedicine, where photothermal effects combined with diagnostic imaging or with drugs have led to new combination therapies.
The delivery system designed by combining nanomedicine with microfluidics will bring new changes in the industry
Despite the broad prospects of nanomedicine, its clinical and commercial output is limited compared to its investment in the field over the past 30-40 years. Problems with formulation synthesis, lack of mass production methods, limited characterization methods, and stringent regulatory requirements are factors that contribute to limited production.
The development of multi-component clinical-scale nanomedicines, the main challenge is the gradual increase in the amount and consistency of product synthesis. Although nanomedicine has made great progress in the preclinical phase, achieving effective clinical performance is the most critical issue. For example, 20 grams of mouse-level drug delivery expands the body’s weight-level drug delivery, as well as synthetic procedures involving multiple typical therapeutic diagnostic steps (eg, ultrasound, centrifugation, sterilization, and lyophilization). It is less efficient and can create consistency problems on a large scale.
In R&D laboratories, the synthesis process can be easily optimized and retested; however, to date, there are no industrial manufacturing solutions available for therapeutic diagnostic nanostructures with multiple components that are reproducible. In addition, understanding the degradation and excretion of multi-component drug delivery systems and nanostructures in vivo is critical, and these factors are unclear, and these operational functions need to be studied before being approved by the FDA for commercial medical practice.
In the past decade, researchers have suggested that microfluidics may have the potential to solve these problems and influence the way drugs are researched and developed. Government agencies are now supporting this attempt.
As we all know, the pharmaceutical industry is slow to update and adapt to new and new technologies. However, with the continuous advancement of microfluidic technology, it is possible to solve the problem of consistent effects of nanomedicine from laboratory to clinical in the future, thereby realizing large-scale commercialization of nanomedicine products. In addition, advances in support technologies such as microfluidics and 3D printing may help the nanomedical industry achieve inexpensive and standardized fluid devices in the future, opening up possibilities for new applications in personalized medicine, drug manufacturing and wearable technologies. .
There is no doubt that nanomedicine has the opportunity to bring better health care outcomes. By 2025, the nanomedicine market is likely to reach $350.8 billion. According to another report from Market Research Engine, the drug delivery market in Europe will reach $536 billion by 2024. The economic incentives received by diagnostic nanomedicine methods should be an important step in stimulating nanomedicine to enter clinical practice.
Nano-pharmaceutical company with metal nanomaterials as the main technical means
Cytimmue Sciences: Patented colloidal nanogold technology for targeted drug delivery in tumors
Founded in 1988, CytImmune has evolved from a successful diagnostic company to a clinical stage nanomedicine company with a core focus on the discovery, development and commercialization of targeted cancer therapy. The company is developing a range of versatile therapeutics that combine known anticancer drugs with its patented colloidal gold tumor targeting nanotechnology.
CytImmune is a global leader in nanomedicine with more than 60 patents for colloidal gold nanotechnology published and pending in the US, EU, Japan and Canada. The clinical trial of the pancreatic cancer treatment drug CYT6091 based on its Aurimune nanomedical platform has been completed.
There are two main types of drugs currently under research at CytImmune Sciences:
Aurmine (CYT6091): The first generation of Aurimune platform nanotherapy CYT-6091 carries gold nanoparticles with TNF molecules attached to the tumor to destroy its blood vessels, enabling subsequent chemotherapy to penetrate the tumor and kill internal cancer cells. In a successful phase I clinical trial, CYT-6091 safely provided patients with a toxic but highly effective dose of the anticancer agent TNF; the dose level was three times the previous maximum tolerated dose. Tissue samples taken 24 hours after CYT-6091 administration showed that the nanomedicine had been concentrated in the tumor tissue rather than in the surrounding healthy tissue.
Phase II clinical trials will be combined with second-line treatment criteria to treat patients with pancreatic cancer. Additional details about the Phase II trial will be posted on the official website.
AuriTol (CYT2100): The second-generation Aurimune platform nanomedicine CYT-21000 carries paclitaxel in addition to gold nanoparticles with TNF molecules attached. Aurimune is currently the only nanotechnology capable of providing both biologics, TNF and the small molecule therapeutic drug paclitaxel, carried by the same nanoparticles.
Nano probes: nanogold labels for medical imaging and microscopic observation
Nano probes was founded in 1990 by Dr. James F. Hainfeld, and he was also alumnus with Dr. Hainfeld at the Brookhaven National Laboratory. Nano probes have designed some highly sensitive detection reagents and techniques for detecting biomolecules. Its 1.4nm nanogold probe has been cited in more than 250 published articles.
Nano probes’ unique gold marking technology uses chemically crosslinked metal clusters and nanoparticles as labels. These tags can be attached to any molecule with reactive groups for detection and localization, such as proteins, polypeptides, oligonucleotides, small molecules, and lipids. The unique FluoroNanogold probe combines Nanogold and fluorescein into one probe and images the sample by fluorescence and electron microscopy.
The new probe can be designed based on any fragment of a naturally occurring biomolecule that is positioned away from the binding site and therefore does not interfere with binding. Colloidal gold particles of conventional immunogold probes are electrostatically adsorbed onto antibodies and proteins. The gold markers of Nano probes are uncharged molecules that crosslink with specific sites on biomolecules. This gives their probes the range and versatility that colloidal gold does not have.
Nanoprobes has developed new technologies that extend the gold label for sensitive and rapid medical diagnosis, as well as a range of auxiliary reagents for chemical amplification, staining and imaging. They have also developed new applications for metal clusters and nanoparticles as components of new materials, sensors and data storage media.
Nanobiotix: Using Nanoparticles to Improve Radiation Therapy
Founded in 2003, Nanobiotix is a leading advanced clinical stage nanomedicine company (France). The company’s introduction of nanophysics into core cell applications has created an efficient and versatile solution that significantly improves patient outcomes.
Nanobiotix’s proprietary NanoXray is designed to increase the effectiveness of radiation for millions of cancer patients. In addition, the company’s immuno-oncology program has the potential to bring new content to cancer immunotherapy.
In March of this year, Nanobiotix received a loan of 14 million euros from the European Investment Bank for the development of NBTXR3, a crystalline nanoparticle used to improve the efficacy of radiation therapy for head and neck cancer. The nanoparticles are injected into tumor cells and then interacted with x-rays to maximize the effectiveness of radiation therapy and reduce preoperative tumor burden.
Other lipid-based nanomedicines that have received widespread attention
AmBisome: the world’s first marketed liposome formulation
AmBisome is the world’s first marketed liposome formulation developed by NeXstar Corporation of the United States and later acquired by Gilead. It was first listed in Europe in 1990 and then listed in the US in 1997. The product is a lyophilized preparation for the treatment of severe deep fungal infections such as kala-azar, yeast disease, coccidioidomycosis, etc., and can also be used for the treatment of aggressive systemic infections caused by Aspergillus, Candida, and the like.
Ambisome has a particle size of about 100 nm, and the drug is stably encapsulated by the negatively charged phospholipid DSPG combined with the positively charged trehalose amine in the amphotericin B structure, so the API amphotericin B is present on the phospholipid bilayer membrane. The cholesterol in the prescription has a hydrophobic effect with the drug molecule.
Bind Therapeutics: Developing Targeted Drugs Containing Docetaxel
BIND Therapeutics (NASDAQ: BIND) is a biotechnology company founded in 2006. Pfizer acquired most of its assets in 2016. Its leading drug, BIND-014, can escape the immune system, reach the disease site, selectively accumulate in diseased tissues and cells, and then release the encapsulated drug at a prescribed rate. The platform is protected by 16 US patents and 50 US patent applications.