Diabetic cardiomyopathy (DCM) is a serious cardiac complication of diabetes that currently lacks specific treatment.
Fibroblast growth factor 21 (
FGF21) has been proved to have cardioprotective effect in DCM. However, the insufficient cardiac delivery effect of
FGF21 limits its application in DCM. Therefore, to improve the therapeutic efficacy of
FGF21 in DCM, an effective drug delivery system is urgently required. In this study,
perfluoropropane (C3F8) and
polyethylenimine (PEI)-doped
poly (lactic-co-glycolic acid) (PLGA) nanobubbles (CPPNBs) were synthesized via double-
emulsion evaporation and
FGF21 was efficiently absorbed (CPPNBs@
FGF21) via the electrostatic incorporation effect. CPPNBs@
FGF21 could effectively deliver
FGF21 to the myocardial tissue through the cavitation effect under low-frequency ultrasound (LFUS). The as-prepared CPPNBs@
FGF21 could efficiently load
FGF21 after doping with the cationic
polymer PEI, and displayed uniform dispersion and favorable biosafety. After filling with C3F8, CPPNBs@
FGF21 could be used for distribution monitoring through ultrasound imaging. Moreover, CPPNBs@
FGF21 significantly downregulated the expression of
ANP, CTGF, and
caspase-3 mRNA via the action of LFUS owing to increased
FGF21 release, therefore exhibiting enhanced inhibition of myocardial
hypertrophy, apoptosis, and interstitial
fibrosis in DCM mice. In conclusion, we established an effective
protein delivery nanocarrier for the diagnosis and prophylactic treatment of DCM. STATEMENT OF SIGNIFICANCE:
Diabetic cardiomyopathy (DCM) is a serious cardiac complication of diabetes that currently lacks effective clinical treatments.
Fibroblast growth factor 21 (
FGF21) can protect cardiomyocytes from diabetic damage, but insufficient cardiac drug delivery limits the application of
FGF21 in DCM. In this study,
perfluoropropane (C3F8) and
polyethylenimine (PEI)-doped
poly (lactic-co-glycolic acid) (PLGA) nanobubbles loaded with
FGF21 (CPPNBs@
FGF21) were developed for the prophylactic treatment of DCM. CPPNBs@
FGF21 could effectively deliver the
FGF21 to the myocardial tissue through the cavitation effect of low-frequency ultrasound (LFUS). Our results indicated that CPPNBs@
FGF21 combined with LFUS could significantly down-regulate the expressions of
ANP, CTGF, and
caspase-3 mRNA, and as a result, it prevented the myocardial
hypertrophy, apoptosis, and interstitial
fibrosis of DCM mice. Overall, we established an effective
protein delivery nanocarrier for the diagnosis and prophylactic treatment of DCM.