Cancer　cell　expresses　abundant　surface　receptors.　These　receptors　are　important　targets　for　cancer　treatment　and　imaging　applications.　Our　goal　here　is　to　develop　nanoparticles　with　cargo　loading　and　tumor　targeting　capability.　Methods:　A　peptide　targeting　at　cancer　cell　surface　receptor　(urokinase　receptor,　uPAR)　was　expressed　in　fusion　with　albumin　(diameter　of　~7　nm),　and　the　fusion　protein　was　assembled　into　nanoparticles　with　diameter　of　40　nm,　either　in　the　presence　or　absence　of　cargo　molecules,　by　a　novel　preparation　method.　An　important　feature　of　this　method　is　that　the　nanoparticles　were　stabilized　by　hydrophobic　interaction　of　the　fusion　protein　and　no　covalent　linking　agent　was　used　in　the　preparation.　The　stability,　the　cargo　release,　in　vitro　and　in　vivo　properties　of　such　formed　nanoparticles　were　characterized　by　transmission　electron　microscopy,　dynamic　light　scattering,　gel　shift　assay,　laser　scanning　confocal　microscopy　and　3D　fluorescent　molecular　tomography.　Results:　The　nanoparticles　were　stable　for　more　than　two　weeks　in　aqueous　buffer,　even　in　the　buffer　containing　10%　fetal　bovine　serum.　Interestingly,　in　the　presence　of　urokinase　receptor,　the　uPAR-targeting　nanoparticle　disintegrated　into　7.5　nm　fragments　and　released　its　cargo,　but　not　the　non-targeting　nanoparticles　made　from　albumin　by　the　same　preparation　method.　Such　nanoparticles　also　showed　higher　uptake　and　cytotoxicity　to　the　receptor-expressing　cancer　cells　in　vitro　and　higher　tumor　accumulation　in　xenografted　tumor-bearing　mice　in　vivo　compared　to　the　non-targeting　nanoparticles.　Conclusion:　Our　results　demonstrate　a　new　function　of　cell　surface　receptor　as　a　responsive　trigger　to　disassemble　nanoparticles,　besides　its　common　use　to　enrich　targeting　agents.　Such　nanoparticles　were　thus　named　receptor-responsive　nanoparticles　(RRNP).　©　Ivyspring　International　Publisher.