We report on the fabrication of self-assembled micelles from ABC-type miktoarm star polypeptide hybrid copolymers consisting of poly(ethylene oxide)

poly(L-lysine)

and poly(

ε

-caprolactone) arms

PEO(-

b

-PLL)-

b

-PCL

and their functional applications as co-delivery nanocarriers of chemotherapeutic drugs and plasmid DNA. Miktoarm star copolymer precursors

PEO(-

b

-PZLL)-

b

-PCL

were synthesized at first via the combination of consecutive "click" reactions and ring-opening polymerizations (ROP)

where PZLL is poly(

ε

-benzyloxycarbonyl-L-lysine). Subsequently

the deprotection of PZLL arm afforded amphiphilic miktoarm star copolymers

PEO(-

b

-PLL)-

b

-PCL. In aqueous media at pH 7.4

PEO(-

b

-PLL)-

b

-PCL self-assembles into micelles consisting of PCL cores and hydrophilic PEO/PLL hybrid coronas. The hydrophobic micellar cores can effectively encapsulate model hydrophobic anticancer drug

paclitaxel; whereas positively charged PLL arms within mixed micellar corona are capable of forming electrostatic polyplexes with negatively charged plasmid DNA (pDNA) at N/P ratios higher than

ca

. 2. Thus

PEO(-

b

-PLL)-

b

-PCL micelles can act as co-delivery nanovehicles for both chemotherapeutic drugs and genes. Furthermore

polyplexes of pDNA with paclitaxel-loaded PEO(-

b

-PLL)-

b

-PCL micelles exhibited improved transfection efficiency compared to that of pDNA/blank micelles. We expect that the reported strategy of varying chain topologies for the fabrication of co-delivery polymeric nanocarriers can be further applied to integrate with other advantageous functions such as targeting

imaging

and diagnostics.