In recent years, anti-tumor peptides have emerged as a research hotspot in the biomedical field due to their unique molecular properties and broad therapeutic potential. Compared to traditional chemotherapy drugs, anti-tumor peptides offer advantages such as low molecular weight, high specificity, low toxicity, and ease of synthesis, providing new possibilities for cancer treatment.
What Are Anti-Tumor Peptides?
Bioactive molecules known as anti-tumor peptides present substantial prospects for cancer treatment. Anti-tumor peptides consist of multiple amino acids bonded together by peptide bonds and function to specifically target tumor cells while blocking tumor growth and metastasis and triggering tumor cell apoptosis. Due to their small relative molecular mass along with high activity and low toxicity properties anti-tumor peptides show great potential for cancer treatment.
Anti-tumor peptides demonstrate diversity regarding their classification and source of origin. Anti-tumor peptides can be divided into two groups depending on their origin: those that come from natural sources and those that are created through synthetic methods. Anti-tumor peptides that occur naturally exist within animals as well as plants and microorganisms. Research shows that some mammalian-derived peptides demonstrate potent anti-tumor effects when tested against lymphoma cells. Synthetic peptides result from chemical synthesis processes and biotechnological production methods. Anti-tumor peptides undergo classification through their structural properties and operational mechanisms which define their distinct functions in cancer treatment.
Comparison of Natural and Synthetic Peptides
Naturally derived anti-tumor peptides offer a wide range of biological activities and are often well-compatible with living organisms due to their evolutionarily optimized structures and functions. However, they also have limitations, such as complex extraction processes, low yields, and short half-lives in vivo due to rapid enzymatic degradation.
Synthetic peptides help overcome these challenges. Advanced synthesis techniques allow precise control over amino acid sequences and structures, enhancing stability and bioactivity. Moreover, chemical modifications can extend the half-life of synthetic peptides and improve their targeting capabilities. For instance, structural modifications can make peptides more resistant to enzymatic degradation, enabling them to exert prolonged effects in the body. Therefore, synthetic techniques play a crucial role in addressing the limitations of natural peptides and expanding the potential applications of anti-tumor peptides.
Key Characteristics and Advantages of Anti-Tumor Peptides
Anti-tumor peptides, typically composed of 10-50 amino acids, exhibit several notable features:
Targeting Specificity: Peptides can precisely bind to tumor cell surface receptors via specific amino acid sequences, enabling highly targeted action.
Low Toxicity: Compared to traditional chemotherapy drugs, peptides have fewer side effects and lower toxicity to the human body.
Ease of Modification: Peptides can be engineered through chemical modifications or genetic techniques to enhance their stability and therapeutic efficacy.
Core Mechanisms of Anti-Tumor Peptides
The anti-cancer effects of anti-tumor peptides involve various mechanisms, with apoptosis induction and membrane disruption being particularly critical. Inducing apoptosis is a key pathway through which anti-tumor peptides drive cancer cells toward programmed cell death. These peptides interfere with the normal physiological processes of tumor cells, ultimately leading to apoptosis. Meanwhile, membrane disruption exploits the unique properties of cancer cell membranes to directly attack and compromise their integrity, causing leakage of cellular contents and eventual cell death.
In addition to these primary mechanisms, anti-tumor peptides also inhibit angiogenesis and modulate the immune system, contributing to their therapeutic effects. Tumor growth and metastasis rely on newly formed blood vessels for nutrient and oxygen supply, and inhibiting angiogenesis can starve tumors, limiting their proliferation and spread. Immune modulation, on the other hand, enhances the body’s immune response against tumors by boosting the recognition and killing capabilities of immune cells.
Apoptosis Induction Pathways
Anti-tumor peptides can trigger apoptosis through multiple pathways. One crucial step involves disrupting mitochondrial membrane potential. When anti-tumor peptides act on cancer cells, they increase intracellular Ca2+ levels, leading to calcium overload and subsequent mitochondrial membrane potential reduction. This imbalance prompts the release of cytochrome C into the cytoplasm, initiating a cascade of apoptotic reactions.
Activation of the Caspase family is another key step in apoptosis induction. Cytochrome C interacts with Caspase-9 and apoptosis-inducing factor-1 to form an apoptotic complex, which subsequently activates Caspase-9 and downstream apoptotic proteins, driving cells toward programmed death. During this process, pro-apoptotic proteins such as Bax increase in expression, while anti-apoptotic proteins like Bcl-2 decrease, disrupting the intracellular balance of apoptosis regulation.
The p53 gene also plays a crucial role in apoptosis regulation. Over half of human tumors harbor p53 mutations, leading to defective apoptotic pathways. Certain anti-tumor peptides can partially restore p53 function by modulating p53-related signaling pathways to induce tumor cell apoptosis. For example, peptides derived from p53 and its associated proteins, such as SMAR1 and p73, can bind to p73, thereby triggering p73-dependent apoptosis and compensating for p53 dysfunction.
By leveraging these diverse mechanisms, anti-tumor peptides offer a powerful and versatile approach to combating cancer, making them a promising area for future therapeutic development.
Targeted Membrane Disruption Models
The targeted membrane disruption models primarily include the barrel-stave model, toroidal pore model, and carpet model. In the barrel-stave model, antitumor peptide molecules aggregate on the cell membrane, forming a barrel-like structure that inserts into the membrane, compromising its integrity. The toroidal pore model involves peptide molecules forming ring-like pores on the membrane, leading to leakage of intracellular contents and ultimately causing cell death. In the carpet model, peptides cover the membrane surface like a carpet and disrupt membrane structure through physical interactions.
Cancer cell membranes exhibit a negative charge and high fluidity, which provides an advantage for the targeted action of antitumor peptides. Due to the overexpression of negatively charged phosphatidylserine and glycosylated mucins on cancer cell membranes, these cells carry a higher net negative charge. Since antitumor peptides are generally positively charged, electrostatic interactions enable them to specifically bind to cancer cell membranes. Additionally, the high fluidity of cancer cell membranes facilitates the insertion and diffusion of peptide molecules, enhancing membrane disruption effects.
Anti-Angiogenesis and Immune Regulation
Anti-Angiogenesis: Antitumor peptides have shown significant success in inhibiting angiogenesis. Some peptides can inhibit the activity of vascular endothelial growth factor (VEGF), a key factor in promoting angiogenesis. By inhibiting VEGF, these peptides reduce tumor blood vessel formation. Other peptides can block the migration of human umbilical vein endothelial cells (HUVECs), a crucial step in the angiogenesis process. By preventing endothelial cell migration, these peptides effectively suppress angiogenesis and cut off the tumor’s nutrient supply.
Immune Regulation: Antitumor peptides can enhance immune responses by activating natural killer (NK) cells, which are essential components of the immune system that directly kill tumor cells. Additionally, peptides can regulate the PD-1/PD-L1 pathway, a key mechanism in tumor immune evasion. By modulating this pathway, these peptides can relieve the tumor-induced suppression of the immune system, enhance immune cell cytotoxicity against tumor cells, and achieve antitumor effects.
Production and Optimization Strategies for Antitumor Peptides
In the production and optimization of antitumor peptides, solid-phase synthesis and recombinant DNA technology are the mainstream methods. Solid-phase peptide synthesis (SPPS) builds peptides step-by-step on a solid support, offering advantages such as rapid synthesis, high purity, and automation capability. This method precisely controls peptide sequences and is suitable for short-chain peptide synthesis. Recombinant DNA technology, on the other hand, introduces peptide-encoding genes into host cells, enabling peptide production through the host’s expression system. This approach is particularly advantageous for synthesizing complex and long-chain peptides.
AI-assisted design has introduced new strategies for the development of antitumor peptides. Artificial intelligence algorithms can predict and optimize peptide structures and activities, improving research and development efficiency. Long-acting formulations are also being developed to address the issue of peptides’ short half-life in vivo. By encapsulating peptides in specific carriers, controlled release can be achieved, prolonging their therapeutic effects.
Comparison of Mainstream Production Techniques
Common peptide production methods include enzymatic hydrolysis, microbial fermentation, and SPPS, each with distinct efficiency and cost considerations.
Enzymatic hydrolysis utilizes enzymes to break down proteins into peptides. While relatively simple to operate, this method has low efficiency, and it is challenging to control product purity and activity, making it costly.
Microbial fermentation involves using microbial metabolism to produce peptides. It offers high yield and low cost but requires precise control of fermentation conditions, and product separation and purification can be complex.
SPPS excels in rapid synthesis and high purity, allowing precise sequence and structural control. However, its efficiency and cost may be limited for long-chain peptide synthesis.
Recombinant technology has clear advantages for long-chain peptides, as it allows genetic engineering methods to introduce peptide-encoding genes into host cells, achieving high-yield production while enabling modifications that enhance peptide activity and stability.
Structural Modification and Delivery Systems
To enhance the stability and bioavailability of antitumor peptides, structural modifications and delivery system innovations are essential.
Lipid Nanoparticles (LNPs): Lipid nanoparticles (LNPs) serve as a common delivery carrier, encapsulating peptides within a stable nanoparticle structure. LNPs exhibit excellent biocompatibility and targeting ability, protecting peptides from enzymatic degradation and extending their circulation time in the body. Additionally, LNPs can bind to receptors on tumor cell surfaces, enabling targeted delivery and enhancing antitumor efficacy.
Targeting Ligand Modification: Another crucial strategy is targeting ligand modification, where ligands are conjugated to peptides to enable specific binding to tumor cell receptors. This modification improves targeting efficiency and affinity. For example, tumor-specific antibodies or peptide fragments can be attached to antitumor peptides, guiding them precisely to tumor sites and enhancing their cytotoxic effects. These strategies provide strong support for the clinical application of antitumor peptides.
Peptide Modification Services at Creative Peptides
Applications of Antitumor Peptides
Drug Delivery Systems: The immense potential of peptides in drug delivery systems has been clearly demonstrated by research results. Research indicates that peptides function as delivery vehicles that transport chemotherapy drugs and immunomodulators directly to tumor tissues to enhance treatment effectiveness while reducing adverse effects. pH-sensitive peptide-based nanomicelles respond to tumor microenvironment pH changes by enabling controlled drug release.
Immunotherapy: The field of immunotherapy has benefited from substantial advancements in the use of peptides. Chiral peptide hydrogel vaccines function similarly to multiple-dose injections by continuously activating the immune system which leads to stronger antitumor responses.
Recent developments demonstrate antitumor peptides as groundbreaking elements in contemporary cancer therapy.
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