A New pH-Sensitive Peptide for Drug Delivery

The drug delivery system (DDS) is a technical system that comprehensively regulates the distribution of drugs in organisms in space, time, and dose. The goal is to deliver the right amount of drug to the right place at the right time, thereby increasing the utilization efficiency of the drug, improving the efficacy, reducing the cost, and reducing the toxic and side effects. Drug delivery needs to achieve the following effects: drug-controlled release, drug targeting, enhancement of drug stability, regulation of drug metabolism time, promotion of drug absorption, and passage of various biological barriers. The ultimate goal of drug delivery is to improve the drug's physicochemical properties, change the drug's kinetics and metabolic behavior in the body, and achieve better pharmacodynamics and efficient delivery of the drug through formulation means.

Ineffective cell delivery is one of the key issues hindering the development of new drugs. Biofilms are lipophilic, a major obstacle to drug penetration into cellular targets. Many drugs that have good therapeutic effects on significant diseases have hydrophilic or macromolecular structures, so they cannot effectively reach their target sites in cells. Therefore, to improve the targeting of drugs, it is necessary to optimize drug delivery and enhance delivery efficiency. Cell-penetrating peptides, CPPs, are a class of powerful drug transmembrane delivery carriers. CPPs are hydrophilic oligopeptides that carry active macromolecules into the cytoplasmic matrix and/or the nucleus, making them perfect drug delivery carriers. However, cell-penetrating peptides also have some disadvantages as a vehicle for drug delivery, such as low targeting efficiency. Therefore, improving the targeting efficiency of drug delivery carriers.

Alterations in the acidic pH of the tumor microenvironment caused by tumor cell metabolism are characteristic of abnormal cell-to-cell interactions and disruption of homeostasis. This pH change is due to the large amount of lactic acid produced by glycolysis in the tumor microenvironment. Studies have shown that the pH 6-6.6 acidic environment formed by high concentrations of lactic acid is essential for tumor cell metastasis, angiogenesis, and treatment resistance. However, rational use of the acidic microenvironment of tumors could also be an excellent way to increase drug targeting. Recently, researchers have optimized the drug delivery system of cell-penetrating peptides by exploiting the acidic microenvironment of tumor cells. This optimized drug delivery system can effectively enhance drug delivery efficiency, improve drug targeting and internalization, and has excellent potential in developing drug delivery.

Figure 1. Model of Cell Penetrating Peptide drug delivery. ^[1]

The Advantages of this platform include the following:

Improve drug targeting
Improve drug delivery efficiency
Improve the efficiency of cancer treatment

Potential Applications

Vaccine Development
Immunity Therapy
Drug Delivery

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Reference

Kim GC, Cheon DH, Lee Y. Challenge to overcome current limitations of cell-penetrating peptides. Biochim Biophys Acta Proteins Proteom. 2021 Apr;1869(4):140604. doi: 10.1016/j.bbapap.2021.140604.