Abstract
To circumvent the severe cytotoxicity and drug resistance of chemotherapeutics in cancer chemotherapy, we rationally designed an electrospun nanofibrous delivery system for the codelivery of the doxorubicin (DOX) and small interfering ribonucleic acid (siRNA) to improve antitumor activity and mitigate DOX drug resistance. DOX was intercalated into nanolamellar hydroxyapatite (LHAp), which was incorporated into electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers, and finally, the DOX-intercalated LHAp/PLGA scaffold was coated with polydopamine (PDA) followed by immobilization with siRNA/polyethyleneimine (PEI) complexes. Benefiting from its intrinsic degradability, the scaffold demonstrated pH-responsive release behavior, leading to the simultaneous delivery of DOX and siRNA. Consequently, the codelivery scaffold demonstrated enhanced therapeutic efficiency in vitro and in vivo compared with the scaffold loaded with single drug due to the combined effects of DOX and siRNA and did not show toxicity or side effects in mice. Therefore, it is a safe and effective strategy for preventing postsurgical tumor recurrence.
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