Chemotherapy　is　currently　one　of　the　promising　therapeutic　methods　for　non-small-cell　lung　cancer　(NSCLC),　but　the　emergence　of　multidrug　resistance　(MDR)　is　the　greatest　obstacle　to　efficient　drug　delivery　for　successful　chemotherapy.　Nanotechnology-based　drug　delivery　holds　great　promise　to　promote　intracellular　drug　delivery　to　reverse　MDR.　In　this　work,　we　used　our　previously　synthesized　ursolic　acid　(UA)　derivative,　FZU-03,010　(F3),　to　prepare　nanodrugs　of　F3　with　different　architectures　and　study　the　role　of　the　structure　on　the　physiochemical　properties　and　the　biological　effects　against　A549　and　its　PTX-resistant　A549/PTX　lung　cancer　cells.　Using　different　preparation　methods,　amphiphilic　F3　could　self-assemble　into　different　structures　such　as　nanoaggregates　(F3-NA),　vesicles　(F3-VC),　or　nanoparticles　(F3-NP)　with　different　physiochemical　properties.　The　self-assembled　nanodrugs　could　be　utilized　for　the　entrapment　of　fluorophores　and　showed　different　cellular　uptake　efficiencies.　The　cytotoxicity　results　demonstrated　that　compared　with　UA,　F3-NA　and　F3-NP　could　suppress　A549　and　A549/PTX　cells　viability　more　potently　at　lower　concentration.　In　addition,　F3-NA　and　F3-NP　could　induce　G1　cell　cycle　arrest,　cell　apoptosis　and　caspase-3　activation　more　efficiently　than　that　of　UA.　Furthermore,　F3-NA　and　F3-NP　could　effectively　inhibit　PI3K/Akt　pathway　and　decrease　the　expression　of　Bcl-2　and　the　cell　cycle-dependent　kinase　inhibitors　p-ERK1/2　and　Cyclin　D1　in　both　A549　and　A549/PTX　cells.　In　conclusion,　our　results　suggest　that　the　UA　derivative　F3　is　more　potent　in　inhibiting　cancer　cell　proliferation,　and　F3-NA　and　F3-NP　have　the　potential　to　be　developed　as　a　therapeutic　agent　for　resistant　NSCLC　cells.