Step on the point of delivery of chemotherapy drugs: click on the new use of chemistry

News Events recently invented a new use of click chemistry to deliver chemotherapy drugs to tumor tissue.
the technology platform, called Click Activated Protodrugs Against Cancer (CAPAC), has two components, one is a water-soluble pre-drug injected directly into the tumor tissue hyaluracintic acid (NaHA) polypolymer derivative SQL70, and the other is a chemotherapy drug.
NaHA was added to a fragment called tetrate, while the chemotherapy drug was given a carbonate to a transcycline.
the two fragments can have a ring-plus reaction in the body, the product of which is unstable and can break down and release chemotherapy drugs.
the authors injected NaHA derivatives into tumor tissue and then systematically gave pre-chemotherapy drugs.
because the pre-drug itself is less active and toxic, it can be given more than 10 times the dose.
The authors derived four traditional chemotherapy drugs (amoelin, yew alcohol, etoposide, gixitabin) with this technique, and the derivative SQP33 of amycin worked best, not only increasing the dose by 10 times, but also greatly improving the water solubility.
mouse experiments showed that the pre-drug could indeed be activated by SQL70.
Drug source analysis Although targeted drugs and immunotherapy are flooding into tumor therapy, traditional chemotherapy drugs remain an important pillar because they have no biomarker restrictions, are more durable than targeted therapies, and have higher response rates than immunotherapy.
that although some adaptive chemotherapy is pushed from the front line to the back, patients often end up needing chemotherapy.
of course chemotherapy has its own problems, one is that the treatment window is too small, the system is very toxic.
is generally poor water solubility, forced to use dangerous dosage forms.
such as yew alcohol injections because the accessories may cause allergic reactions patients must use steroid drugs in advance, increasing the risk of infection.
drug is a common technique to solve the water solubility, the design idea is to add a soluble group to the drug molecule, to the body is metabolized to release the original drug.
Expanded treatment window through targeted delivery is a major precursor in the pharmaceutical industry, from ADC, CAR-T, dual-specific antibodies to nano-preparations, TME induced activation is to selectively increase the concentration of drugs in tumor tissue.
these existing technologies depend entirely on the intrinsic properties of tumors, either tumor-specific antigens, or TME-specific properties such as high permeability and high acidity.
today's technique is to artificially send an undercover agent to the tumor tissue, which is then combined with the drug before it enters the system, to release lethal drugs in the tumor tissue.
technology is equivalent to continuous drips in the tumor, or intra-tumor release preparations, and the drug exposure may be smoother than injecting tumor drugs in a direct tumor.
of course, the technology also faces a lot of uncertainty.
is security, NaHA security does not mean that its derivatives are also safe.
is the complex metabolism of pre-drugs, increasing the risk of toxic metabolites and drug interactions.
although poor water solubility of chemotherapy is a historical problem, but water-soluble pre-drug market is not many, although the technology is simpler than today's design, indicating that the pre-drug itself is difficult.
is whether the efficiency of this click reaction in the body can beat the drug metabolic mechanism and significantly increase the concentration of tumor tissue drugs.
of course, because the chemotherapy window is very narrow, any improvement may significantly expand the scope of treatment.
such as albumin yew alcohol only increased by 30% over the accumulation of yew alcohol in tumor tissue, but clinical differentiation has been shown.
's most recent victory was in a battle with Tecentriq, which was approved for listing and clinically failed.
click chemistry is a concept that Nobel Prize-winning Professor Sharpless has proposed for 20 years, that some chemical reaction substrates are highly specific and do not participate in other reactions except to see each other react efficiently.
today's so-called reverse electronic demand Diels-Alder response is one of the few click reactions.
reaction can occur in body temperature, neutral aqueous solutions, so it is used in many biological system studies.
the technique is mainly used to find target proteins that interact with drugs in cells, and target delivery drugs are relatively novel.
is certainly more challenging, as the concentration of exposure to drugs in the body is usually much lower than that required by normal chemical reactions, so efficiency is a challenge.
the chemical reaction and the difficult carbon bond formation reaction than its appearance, but in fact, it is very useful.
the study will attract more chemists to invent more efficient click reactions.