Malignant tumor is one of the most serious diseases threatening human life and health.It is still globally maintaining high incidence rate and mortality.There are six biological characteristics of malignant tumors:continuous proliferation, anti growth inhibition,anti apoptosis,anti cell aging,induction of angiogenesis and active transport.These six characteristics are necessary in the multi-step development process and reflecting the complexity of tumor diseases. In-depth study of these six characteristics will help us to develop anti-tumor drugs with a focused goal.
Despite the breakthrough in immunotherapy in recent years, surgery, radiotherapy and chemotherapy are still widely used in clinical cancer treatment. Finding a safe, reasonable and effective tumor treatment method is an urgent problem in the field of tumor treatment.
Compared with other anti-cancer treatment, antitumor peptides have become a research hotspot in the field of anticancer in recent years because of their many advantages:
|Operation||Radiotherapy||Chemical drugs||Protein drugs||Antitumor peptide|
• Unable to eliminate cancer cells completely
• Difficult in some body part
• High cost of treatment
• Long treatment cycle
• More complications
• Can't eliminate cancer cells completely
• Nonspecific, will kill normal cells of human body
• Some tumors are not sensitive to drugs
• Cancer cells will recur or metastasize
• High price
• Easy to cause autoimmune reaction
• High molecular weight and complex structure
• Accurate target specificity
• Easy synthesis and sequence optimization
• Low molecular weight lead to high cell permeability
• Low toxicity
There are many sources of anti-tumor peptides, including antimicrobial peptides, peptide hormones, peptide toxin and endostatin. More than 800 peptide drugs in preclinical research and development stage,and over 30 kinds of anti-tumor peptide drugs in clinical trials. The research of anti-tumor peptide mainly selects active peptide molecules with less than 50 amino acids.
At present the development of antitumor peptides focuses on the following areas:
Most of these antitumor peptides come from antimicrobial peptides.It plays an anti-cancer role by inducing tumor cell apoptosis, inhibiting tumor neovascularization, inhibiting tumor cell growth and metastasis, and anti-tumor immunotherapy.The optimization of these peptides focuses on the following aspects:
• Extend half-life:
Sequence modification,such as acetylation, D- amino acid, cyclization or α - helix stapled peptide to enhance its anti enzymatic ability.
Connect peptide with high molecular compounds, such as PEG, PAS, HSA to increase their hydrodynamic radius.
• Alter dosage form
About 80% of the protein peptide drugs were injected.The drug delivery system (DDS) can deliver the drug to the specific tissue in a certain time by changing the preparation method.It can also improve the targeting of the drug and reduce the side effects of peptide.
2. Peptide Carrier
Peptides as nano carriers of antitumor drugs, have unique advantages in targeted drug delivery, drug sustained release, drug dosage reduction and adverse drug reactions reduction.
•Targeted peptide(THP) .a small peptide containing 3-10 amino acids.It can be used as a tumor related diagnostic reagent or as a target molecule to guide anti-tumor drugs into the tumor site to play an anti-tumor effect, reduce the toxic side effects of drugs and increase the distribution of drugs in the tumor site.
•Cell-penetrating peptide(CCP).Most CPPs are small peptides rich in arginine and lysine (most of them are positively charged and pH is close to neutral).Usually connected with nanoparticles, proteins, nucleic acids and other active anti-tumor drugs in the form of covalent or non covalent, through endocytosis or transmembrane transduction to play a role in the cell.
A kind of peptides with highly ordered nanostructures such as nanofibers, nanoparticles and nanotubes are self-assembled by non covalent bonds such as hydrophobic interaction, hydrogen bond and van der Waals force.These self-assembled peptides can be used as drug carriers to improve drug properties, slow release and targeting, and have good biocompatibility and low toxicity.
3. Peptide Vaccine
With the development of biotechnology, the production of tumor peptide vaccine is becoming more and more perfect. Tumor peptide vaccine has become a new tumor therapy because of its advantages such as small side effects and accurate targeting. It has a broad application prospect in the field of tumor therapy.
According to the known or predicted amino acid sequence of a certain antigen epitope in pathogen antigen gene, the vaccine was produced by chemical peptide synthesis method. Peptide vaccine is an important direction of vaccine research at present and it has been developed for the peptide vaccine of HIV and HCV.
Because peptide vaccine is completely synthesized, there is no problem of virulence recovery or incomplete inactivation. In particular, some microbial pathogens can not get enough antigens through in vitro culture. Peptides, as immunogens that cause immune response of effector cells in vivo will become a new type of vaccine.
4. Tumor cell probe tool
Peptides can be used as molecular probe tools for molecular diagnosis and imaging of tumors.Molecular imaging technology can sense and detect cellular and molecular processes in vivo remotely and non invasively. The radiolabeled peptides can be used as biomarkers for different types of tumor imaging, providing a new tool and method for early detection of tumor.
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