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Charge and Size Dual Switchable Nanocage for Novel Triple-Interlocked Combination Therapy Pattern
Rui Yang1, Zipeng Zhang1, Shunli Fu1
1Department of Pharmaceutics Key Laboratory of Chemical Biology (Ministry of Education) School of Pharmaceutical Sciences Shandong University 44 Wenhuaxi Road Jinan Shandong 250012 China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|October 1, 2020
Summary
A novel pH-triggered nanocage delivers abemaciclib and IMD-0354, enhancing cancer treatment through combined chemotherapy and immunotherapy. This dual-action drug delivery system shows promise for improved antitumor activity.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapy
Background:
- Combination therapy is crucial for improving antitumor activity in cancer treatment.
- Synergistic effects of combined drugs are essential for enhanced efficacy.
- Developing advanced drug delivery systems is key to overcoming treatment limitations.
Purpose of the Study:
- To develop a pH-triggered, dual-switchable nanocage (PA/PI-ND) for co-delivering abemaciclib and IMD-0354.
- To investigate the triple-interlocked combination of chemotherapy, immunotherapy, and chemoimmunotherapy.
- To evaluate the enhanced cellular uptake, tumor penetration, and antitumor efficacy of the PA/PI-ND system.
Main Methods:
- Fabrication of a charge reversal polymer (NGR-PEG-PLL-DMA) for pH-triggered size and charge switching.
- Co-loading of abemaciclib and IMD-0354 into the nanocage system (PA/PI-ND).
- Evaluation of pH-triggered changes in size (180 to 10 nm) and charge (negative to positive) in acidic tumor microenvironments.
- Assessment of cellular uptake, tumor penetration, and antitumor effects, including cell cycle arrest, Treg inhibition, and TAM repolarization.
Main Results:
- The PA/PI-ND system demonstrated pH-triggered charge reversal and significant size reduction in acidic conditions.
- Enhanced cellular uptake and deep tumor tissue penetration were observed.
- The combination therapy exhibited synergistic effects: abemaciclib induced G1 cell cycle arrest, IMD-0354 reduced cyclin D levels, abemaciclib inhibited regulatory T cells, and IMD-0354 promoted M2 to M1 repolarization of tumor-associated macrophages.
- Improved anti-tumor efficiency was achieved through the combined chemoimmunotherapy effects.
Conclusions:
- PA/PI-ND is a promising dual-switchable nanocage for cancer combination therapy.
- The triple-interlocked strategy of chemotherapy and immunotherapy offers enhanced antitumor activity.
- This approach provides a valuable platform for designing future drug delivery carriers and combination cancer therapies.
