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Cryptobiosis-inspired assembly of "AND" logic gate platform for potential tumor-specific drug delivery
Hu Zhou1, Gang He2, Yanbin Sun2
1Shenzhen Maternity and Child Healthcare Hospital, Shandong University, Shenzhen 518028, China.
Abstract:
Developing tumor-specific drug delivery systems with minimized off-target cargo leakage remains an enduring challenge. In this study, inspired from the natural cryptobiosis explored by certain organisms and stimuli-responsive polyphenol‒metal coordination chemistry, doxorubicin (DOX)-conjugated gelatin nanoparticles with protective shells formed by complex of tannic acid and FeIII (DG@TA-FeIII NPs) were successfully developed as an "AND" logic gate platform for tumor-targeted DOX delivery. Moreover, benefiting from the well-reported photothermal conversion ability of TA-FeIII complex, a synergistic tumor inhibition effect was confirmed by treating 4T1 tumor-bearing mice with DG@TA-FeIII NPs and localized near-infrared (NIR) laser irradiation. As a proof of concept study, this work present a simple strategy for developing "AND" logic gate platforms by coating enzyme-degradable drug conjugates with detachable polyphenol‒metal shells.
Insights
This study developed novel doxorubicin (DOX)-conjugated nanoparticles with protective tannic acid-iron (TA-FeIII) shells for targeted cancer drug delivery. These nanoparticles demonstrated synergistic tumor inhibition when combined with near-infrared laser therapy.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Drug Delivery Systems
Background:
- Minimizing off-target drug leakage from tumor-specific delivery systems is a significant challenge.
- Natural cryptobiosis and stimuli-responsive polyphenol-metal coordination chemistry inspire new strategies.
- Doxorubicin (DOX) is a widely used chemotherapeutic agent with potential for targeted delivery.
Purpose of the Study:
- To develop an "AND" logic gate platform for tumor-targeted doxorubicin delivery.
- To create doxorubicin-conjugated gelatin nanoparticles (DG NPs) with protective tannic acid-iron (TA-FeIII) shells.
- To investigate the synergistic tumor inhibition effect of these nanoparticles with near-infrared (NIR) laser irradiation.
Main Methods:
- Synthesis of doxorubicin-conjugated gelatin nanoparticles (DG NPs).
- Formation of protective shells using tannic acid and FeIII complex (TA-FeIII).
- In vivo evaluation of synergistic tumor inhibition in 4T1 tumor-bearing mice using DG@TA-FeIII NPs and NIR laser irradiation.
Main Results:
- Successfully developed DG@TA-FeIII NPs functioning as an "AND" logic gate for tumor-targeted DOX delivery.
- Demonstrated a synergistic tumor inhibition effect in vivo when DG@TA-FeIII NPs were combined with localized NIR laser irradiation.
- Confirmed the photothermal conversion ability of the TA-FeIII complex contributing to the synergistic effect.
Conclusions:
- Presented a simple strategy for creating "AND" logic gate platforms for drug delivery.
- Coating enzyme-degradable drug conjugates with detachable polyphenol-metal shells offers a promising approach for targeted cancer therapy.
- The developed DG@TA-FeIII NPs show potential for enhanced chemothermal treatment of tumors.
