Journal
ACS APPLIED BIO MATERIALS
Volume 3, Issue 4, Pages 2284-2294Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsabm.0c00072
Keywords
combination therapy; synergistic effect; drug self-framed delivery system; MDR cancer; polyphosphazene
Funding
- National Natural Science Foundation of China [51573089, 21704076, 51973160]
- China Postdoctoral Innovation Talent Project
- China Postdoctoral Science Foundation
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Combination therapy is a burgeoning research field due to the advantages of the synergistic contributions from incorporating drugs and promising potentials in the therapy of aggressive tumors with multidrug resistance (MDR). Given the great efforts, it is extremely difficult to coordinate pharmacokinetics between drugs and elucidate the mechanism of synergistic effects. Additionally, limited by the inherent solubility of anticancer drugs, a common strategy for simultaneously delivering various drugs is yet a challenging target. To overcome these, we develop a drug self-framed delivery system (DSFDS) via treating multiple drugs as monomers to constructing cyclomatrix polyphosphazene nanoparticles (CPPZ NPs). Notably, it is a superflexible common platform to realize the rational design of combination therapy, which is verified by delivering doxorubicin (DOX) with mitoxantrone (Mit), resveratrol (RES), curcumin (Cur), and porphyrin (TPP). As a proof of concept, DOX-RES-CysM-CPPZ NP was selected to therapeutic feasibility of DSFDSs. Obvious improvement in killing MDR tumors indicated an efficient combination therapy. The corresponding synergistic mechanism of DOX and RES was also addressed in this work. Throughout cutting-edge research, the drug self-framed delivery system is drawing promising blueprint for combination therapy.
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