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Acid-responsive dextran-based therapeutic nanoplatforms for photodynamic-chemotherapy against multidrug resistance
Lin Liu1, Yanli Bao1, Yu Zhang1
1Department of Chemistry, Northeast Normal University, Changchun 130024, PR China.
Abstract:
Limited by multidrug resistance (MDR) and nonspecific selectivity, free molecular chemotherapies still are inefficient in clinical cancer treatment. Nanoscale therapeutics delivery systems with controllable release capacity have been developed to reverse multidrug resistance and improve anticancer efficacy. Herein, we constructed acid-sensitive dextrin-based nanoplatforms (THDP) to deliver chemotherapies via supramolecular coordination between tetra sodium meso-tetra (sulfonatophenyl)-porphyrin zinc (II) (Zn-TPPS) and histidine modified dextrin-graft-poly (ethylene glycol) (HDP) to reverse multidrug resistance through photodynamic-chemotherapy. The introductions of hydrophilic poly (ethylene glycol) (PEG) not only prevent undesired aggregation under physiological conditions but also enhanced cellular endocytosis effect. Doxorubicin loaded nanoplatforms (THDP@DOX) with a relatively uniform size of average 63 nm exhibited excellent stability in blood circulation. When THDP@DOX was internalized, the acidic intercellular environment could control the chemotherapies release. Moreover, the generated reactive oxygen species by photosensitizer Zn-TPPS with light irradiation could obviously block DOX efflux and ultimately induce apoptosis to effectively reverse multidrug resistance of tumor cells. Meanwhile, the combination of photosensitizers and chemotherapies obviously created an enhanced MDR reversal effect, providing a promising approach for MDR reversal to achieve highly efficient cancer therapeutics.
Insights
This study developed acid-sensitive nanoplatforms combining photodynamic and chemotherapy to overcome multidrug resistance (MDR) in cancer. The nanocarrier effectively delivered drugs and enhanced cancer cell apoptosis, offering a promising strategy for MDR reversal.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Therapeutics
Background:
- Chemotherapy faces limitations due to multidrug resistance (MDR) and poor selectivity.
- Nanoscale delivery systems offer improved control and efficacy for cancer treatment.
Purpose of the Study:
- To construct acid-sensitive dextrin-based nanoplatforms (THDP) for combined photodynamic-chemotherapy.
- To reverse multidrug resistance (MDR) and enhance anticancer efficacy.
Main Methods:
- Supramolecular coordination of Zn-TPPS (photosensitizer) and HDP (histidine-modified dextrin-graft-PEG).
- Loading doxorubicin (DOX) onto the nanoplatform (THDP@DOX) with an average size of 63 nm.
- Utilizing acid-sensitive properties and photodynamic effects for controlled drug release and MDR reversal.
Main Results:
- THDP@DOX showed good stability in circulation and enhanced cellular uptake due to PEG.
- Acidic environments triggered controlled DOX release.
- Photodynamic action of Zn-TPPS blocked DOX efflux and induced apoptosis, effectively reversing MDR.
Conclusions:
- The combined photodynamic-chemotherapy approach using THDP@DOX shows significant potential for reversing MDR.
- This nanoplatform offers a promising strategy for developing highly efficient cancer therapeutics.
