As PNIPAM is temperature - responsive , [ 16 ] siRNA - SS - PNIPAM copolymers can self - assemble into nanoparticles upon heating , with al ower critical solution temperature ( LCST ) of 30 8 8C , 31 8 8C , and 32 8 8Cfor PNIPAM components of 7kDa , 13 kDa , and 19 kDa , respectively ( Supporting Information , Table S2 ) . This enables nanoparticles to control drug loading during the self - assembly process . G el retardation assays show that after siRNA - SS - PNIPAM heating , no free siRNAw as released and all siRNAs tayed in the initial position ( Figure 1a ) , further confirming successful nanoparticle formulation . Dynamic light scattering ( DLS ) measurements show that the formulated nanoparticles ranged in particle size from 126 nm to 135 nm ( Figure 1b and Supporting Information , Table S2 ) while exhibiting very narrow polydispersity index ( PDI ) . Tr ansmission electron microscopy ( TEM ) images further confirmed the particle size . M ore importantly , aclear vesicular morphology , w ith an empty interior and as olid layer , was observed in nanoparticles derived from PNIPAMs of three different molecular weights ( Figure 1cand Supporting Information , Figure S4 ) , indicating the successful formation of siRNAsome . F urthermore , t he siRNAsomes are very stable under physiological condition , their particle size was constant and no siRNAr elease was observed even after up to 7days of storage ( Supporting Information , Figure S5 ) . Thes iRNAsomes derived from PNIPAMs of 19 kDa in molecular weight showed the best dilution stability ( lowest critical aggregation concentration , CAC ; Supporting Information , Table S2 ) . Using PNIPAM of this molecular weight , the drug - loading utility of siRNAsome was confirmed by performing an encapsulation experiment using the hydrophilic drug doxorubicin hydrochloride ( Dox·HCl ) , the hydrophobic drug docetaxel ( DTX ) , and the hydrophilic protein bovine serum albumin ( BSA ) . As shown in Tables S3 in the Supporting Information , successful encapsulation of Dox·HCl , DTX , and BSA was achieved during the siRNAsome fabrication process . U sing siRNA - SS - PNIPAM copolymer , upon heating , loading efficacies of approximately 37 % , 43 % , and 33 % ( for Dox·HCl , DTX , and BSA , respectively ) were achieved at at heoretical drug loading content of 20 wt.% . These data confirm that the siRNAsome Scheme 1 . Illustration of siRNAsomef ormation , composition , and function . T > LCST = Temperatureg reater than the lower critical solution temperature . nanostructure can serve as au niquely versatile carrier for therapeutic agents with diverse chemical properties and types .