Current Understanding of Interactions between Nanoparticles and ABC Transporters in Cancer Cells
Jian Yin1, Xudong Deng2, Jie Zhang1,3
1CAS Key Lab of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu 215163, China.
Background:
ATP-binding cassette (ABC) transporters-mediated multidrug resistance (MDR) remains the major obstacle for effective cancer therapy. Nanoparticles (NPs)-based delivery systems are promising to overcome MDR, but only a few of them have been accepted for clinical treatment, which should be due to their insufficient transportation and potential toxicity. In this respect, more and more attentions are being attracted on the interactions between NPs and ABC transporters, which hold a key role in the treatment of MDR cancer and the toxicity of NPs. However, there are no systematic reviews about such interactions, especially about their corresponding mechanism.
Methods:
We undertook extensive search of PubMed databases for peer-reviewed literatures using focused review questions. The retrieved papers were mostly published within the 5 years (84 of 104) and all with an impact factor above 2. First, this review focused on the current knowledge of ABC transporters involved in MDR and their inhibitors. Then, we reviewed the most recent literature about the inhibitory effects of organic NPs' excipients on ABC transporters and the direct interactions of inorganic NPs with ABC transporters. The major elements of obtained papers were described and classified depending on the structure of NPs.
Results:
Both organic and inorganic NPs can inhibit the function of ABC transporters, but based on different mechanisms. The effects of organic NPs are caused by several excipients like surfactants, polymers, lipids and cyclodextrin. Meanwhile, inorganic NPs usually act as the substrates of ABC transporters and competitively inhibit the efflux of drugs. These phenomena are interesting and worth investigating.
Conclusion:
The finding of this review confirmed the potential interactions between NPs and ABC transporters. These phenomena are interesting and worth investigating, and a knowledge of related mechanism would not only be important for the clinical therapies toward overcoming cancer MDR, but also help the treatment of other diseases like tuberculosis, AIDS, and central nervous system disorders, whose drugresistance was also related to ABC transporter-mediated efflux.
Insights
Nanoparticles (NPs) can inhibit ATP-binding cassette (ABC) transporters, which mediate multidrug resistance (MDR). Understanding these interactions is key for improving cancer therapy and treating other ABC transporter-related diseases.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Pharmacology
Background:
- Multidrug resistance (MDR) mediated by ATP-binding cassette (ABC) transporters hinders effective cancer therapy.
- Nanoparticle (NP)-based delivery systems show promise for overcoming MDR but face challenges in clinical translation due to transport limitations and toxicity.
- Interactions between NPs and ABC transporters are crucial for both MDR cancer treatment and NP toxicity, yet systematic reviews on these mechanisms are lacking.
Purpose of the Study:
- To systematically review the interactions between nanoparticles and ATP-binding cassette (ABC) transporters.
- To explore the mechanisms by which nanoparticles influence ABC transporter function.
- To assess the implications of these interactions for overcoming multidrug resistance (MDR) in cancer and other diseases.
Main Methods:
- Conducted a comprehensive literature search of PubMed for peer-reviewed articles published within the last five years.
- Focused on studies investigating ABC transporters in MDR, their inhibitors, and the effects of both organic and inorganic NPs on ABC transporters.
- Classified and described NP elements based on their structure and interaction mechanisms.
Main Results:
- Both organic and inorganic NPs demonstrate the ability to inhibit ABC transporter function through distinct mechanisms.
- Organic NPs exert their effects via excipients such as surfactants, polymers, lipids, and cyclodextrins.
- Inorganic NPs often act as substrates for ABC transporters, competitively inhibiting drug efflux.
Conclusions:
- Confirmed significant interactions between NPs and ABC transporters, highlighting their potential therapeutic relevance.
- Further investigation into the mechanisms underlying these NP-ABC transporter interactions is warranted.
- Understanding these mechanisms can advance clinical therapies for cancer MDR and other diseases involving ABC transporter-mediated drug resistance, including tuberculosis, AIDS, and CNS disorders.
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