Purpose:　Renal　cell　carcinoma　(RCC)　is　the　most　common　and　lethal　type　of　urogenital　cancer,　with　one-third　of　new　cases　presenting　as　metastatic　RCC　(mRCC),　which,　being　the　seventh　most　common　cancer　in　men　and　the　ninth　in　women,　poses　a　significant　challenge.　For　patients　with　poor　prognosis,　temsirolimus　(TEM)　has　been　approved　for　first-line　therapy,　possessing　pharmacodynamic　activities　that　block　cancer　cell　growth　and　inhibit　proliferation-associated　proteins.　However,　TEM　suffers　from　poor　water　solubility,　low　bioavailability,　and　systemic　side　effects.　This　study　aims　to　develop　a　novel　drug　formulation　for　the　treatment　of　RCC.　Methods:　In　this　study,　amphiphilic　block　copolymer　(poly(ethylene　glycol)　monomethyl　ether-poly(beta-amino　ester))　(mPEG-PBAE)　was　utilized　as　a　drug　delivery　vehicle　and　TEM-loaded　micelles　were　prepared　by　thin-film　hydration　method　by　loading　TEM　inside　the　nanoparticles.　Then,　the　molecular　weight　of　mPEG-PBAE　was　controlled　to　make　it　realize　hydrophobic-hydrophilic　transition　in　the　corresponding　pH　range　thereby　constructing　pH-responsive　TEM-loaded　micelles.　Characterization　of　pH-responsive　TEM-loaded　nanomicelles　particle　size,　potential　and　micromorphology　while　its　determination　of　drug-loading　properties,　in　vitro　release　properties.　Finally,　pharmacodynamics　and　hepatorenal　toxicity　were　further　evaluated.　Results:　TEM　loading　in　mPEG-PBAE　increased　the　solubility　of　TEM　in　water　from　2.6 μg/mL　to　more　than　5　mg/mL.　The　pH-responsive　TEM-loaded　nanomicelles　were　in　the　form　of　spheres　or　spheroidal　shapes　with　an　average　particle　size　of　43.83　nm　and　a　Zeta　potential　of　1.79　mV.　The　entrapment　efficiency　(EE)　of　pH-responsive　TEM　nanomicelles　with　12.5%　drug　loading　reached　95.27%.　Under　the　environment　of　pH　6.7,　the　TEM　was　released　rapidly　within　12 h,　and　the　release　rate　could　reach　73.12%　with　significant　pH-dependent　characteristics.　In　vitro　experiments　showed　that　mPEG-PBAE　preparation　of　TEM-loaded　micelles　had　non-hemolytic　properties　and　had　significant　inhibitory　effects　on　cancer　cells.　In　vivo　experiments　demonstrated　that　pH-responsive　TEM-loaded　micelles　had　excellent　antitumor　effects　with　significantly　reduced　liver　and　kidney　toxicity.　Conclusion:　In　conclusion,　we　successfully　prepared　pH-responsive　TEM-loaded　micelles.　The　results　showed　that　pH-responsive　TEM-loaded　micelles　can　achieve　passive　tumor　targeting　of　TEM,　and　take　advantage　of　the　acidic　conditions　in　tumor　tissues　to　achieve　rapid　drug　release.　©　2024　Wang　et　al.