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Smart Cancer-Targeting and Super-Sensitive Sensing of Eu3+/Tb3+-Induced Hyaluronan Characteristic Nano-Micelles with
Yupeng Bi1, Longlong Li1, Jin Liu1
1Institute of Hybrid Materials, National Center of International Joint Research for Hybrid Materials Technology, National Base of International Science & Technology Cooperation on Hybrid Materials, Qingdao University, 308 Ningxia Road, Qingdao 266071, China.
Abstract:
To avoid the critical problems of effective drugs not being carried to their targeted cancers and their quantity and location not being sensed in situ, this work presents a completely new innovative strategy to achieve both smart cancer targeting (SCT) and super-sensitive sensing (SSS), where one drug carrier works for effective drug loading and release. Herein, malignant melanoma treatment is used as an example of reliable detection and effective therapy. We report two characteristic dumbbell-like nano-micelles and spherical-like nano-micelles of hyaluronan induced by the Eu3+/Tb3+ complexes for effective drug loading and release, respectively. These special Eu3+/Tb3+-loaded nano-micelles (marked as ENM and TNM) have strong and sharp red/green luminescence that can sensitively detect the malignant melanoma drug dacarbazine through changes in fluorescence intensity. Cytotoxicity experiments confirmed that both ENM and TNM are not toxic to normal cells at very high concentrations of 4 mM. However, when loaded with cancer drugs (D-ENM and D-ENM), they both killed cancer cells with more than 40% efficacy at this concentration. The in vivo experiments confirmed that D-ENM and D-TNM can effectively target cancer cells in tissue and effectively impede cancer growth. The detection limits of ENM and TNM in sensing cancer drugs can reach 0.456 μg/mL and 0.139 μg/mL, respectively. Therefore, the reported Eu3+/Tb3+-induced hyaluronan nano-micelles (ENM and TNM) are distinguished carriers of this cancer drug and excellent in situ sensors, and they have highly therapeutic effects with extremely low toxicity to normal cells.
Insights
This study introduces novel hyaluronan nano-micelles using Eu3+/Tb3+ for smart cancer targeting and sensing. These nano-micelles effectively deliver drugs and monitor cancer treatment with minimal toxicity.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapeutics
Background:
- Effective cancer drug delivery faces challenges in targeting and in situ monitoring.
- Developing smart drug carriers is crucial for improving therapeutic efficacy and reducing side effects.
Purpose of the Study:
- To develop novel hyaluronan nano-micelles for smart cancer targeting (SCT) and super-sensitive sensing (SSS).
- To demonstrate the potential of these nano-micelles in malignant melanoma treatment and drug monitoring.
Main Methods:
- Synthesis of dumbbell-like (ENM) and spherical-like (TNM) hyaluronan nano-micelles induced by Eu3+/Tb3+ complexes.
- Evaluation of drug loading and release capabilities.
- Assessment of luminescence properties for dacarbazine detection.
- In vitro cytotoxicity assays on normal and cancer cells.
- In vivo experiments to confirm targeting and therapeutic effects.
Main Results:
- Eu3+/Tb3+-loaded nano-micelles (ENM and TNM) exhibited strong red/green luminescence.
- Nano-micelles showed high sensitivity in detecting dacarbazine, with detection limits as low as 0.139 μg/mL.
- Cytotoxicity studies confirmed negligible toxicity to normal cells at high concentrations.
- Drug-loaded nano-micelles (D-ENM, D-TNM) demonstrated over 40% cancer cell killing efficacy.
- In vivo studies confirmed effective targeting of cancer cells and inhibition of tumor growth.
Conclusions:
- Eu3+/Tb3+-induced hyaluronan nano-micelles serve as effective drug carriers and in situ sensors for cancer therapy.
- These nano-micelles offer highly therapeutic effects with extremely low toxicity to normal cells.
- The developed system shows significant promise for advanced cancer treatment strategies.
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