Poly　γ-glutamic　acid　(γ-PGA)　is　attractive　due　to　its　desirable　biological　properties　such　as　nontoxicity,　excellent　biocompatibility,　and　minimal　immunogenicity.　Additionally,　γ-PGA　could　be　recognized　by　γ-glutamyl　transpeptidase,　which　is　regarded　as　a　potential　biomarker　for　many　tumors.　In　this　study,　we　have　developed　a　new　biodegradable,　reduction　sensitive,　and　tumor-specific　gene　nano-delivery　platform　consisting　of　a　cationic　carrier　(SSBPEI)　for　siRNA　condensation,　mPEG　shell　for　nanoparticle　stabilization,　and　γ-PGA　for　accelerated　cellular　uptake.　Disulfide　bonds　(-SS-)　could　be　reduced　specifically　in　the　tumor　environment,　which　is　full　of　reductants　such　as　glutathione　reductase.　Conjugating　polyethylene　glycol　(PEG)　to　the　γ-PGA　led　to　the　formation　of　mPEG-g-γ-PGA,　with　a　decreased　positive　charge　on　the　surface　of　SSBPEI@siRNA　and　substantially　higher　stability　in　an　aqueous　medium.　As　a　result,　mPEG-g-γ-PGA/SSBPEI@siRNA　nanoparticles　could　protect　siRNAs　from　RNase　A　degradation　and　release　siRNAs　in　a　reduction　sensitive　way.　The　multifunctional　delivery　system　was　shown　to　silence　the　Survivin　gene　and　further　promote　chemotherapeutic　drug-induced　apoptosis　in　the　A549　NSCLC　cell　line　efficiently,　thereby　representing　a　novel　promising　platform　for　the　delivery　of　siRNAs.　©　2020　Elsevier　B.V.