It is well-known that the Dengue fever virus undergoes a distinct morphological transition from topologically smooth particles to 'bumpy' particle on increasing the temperature from that of the mosquito carrier (28 C) to that of the human host (37 C). This virus also possesses pH-sensitive surface domains that undergo conformational changes during infection which facilitates exit from the endosomes. Herein we take a bio-inspired approach to design synthetic Dengue virus-mimicking nanoparticles to target triple-negative (TN) breast cancer cells that overexpress SR-B1 scavenger receptors. Thus, sterile pH-responsive methacrylic ABC triblock copolymer vesicles were prepared in aqueous solution via polymerization-induced self-assembly. Microphase separation between two enthalpically-incompatible hydrophobic membrane-forming blocks produced a well-defined framboidal morphology, with surface globules of $28 nm diameter protruding from the membrane. The hydrophilic stabilizer block comprises 97% hydroxyl-functionalized chains and 3% phosphorylcholine-functionalized chains, with the latter being critical for selective intracellular uptake. These framboidal vesicles remain intact at neutral pH but become swollen and cationic at pH 5-6 because the tertiary amine residues in the hydrophobic C block become protonated. We demonstrate that such nanoparticles enable selective targeting of TN breast cancer cells. This is because such malignant cells overexpress SR-B1 receptors for naturally-occurring phospholipids and hence take up the phosphorylcholine-decorated framboidal vesicles preferentially. In contrast, negligible cell uptake is observed over the same time period for both human dermal fibroblasts and normal breast cancer cells that minimally express the SR-B1 receptor.Moreover, we show that genetic material within such pH-responsive framboidal vesicles can be efficiently delivered to the cell nuclei while maintaining high cell viability. ; Tel: +44 (0)114 222 1093 † Electronic supplementary information (ESI) available: Full experimental details for the synthesis and characterization of the copolymer vesicles, assigned 1 H NMR spectra, GPC traces, bioburden and MTT test results, ow cytometry scavenger receptor expression studies, co-localization studies and a table of structural parameters obtained from SAXS analysis are provided. See Fig. 1 Synthesis of fluorescently-labelled PGMA 58 -P(HPMA 300 -stat-GlyMARh 1 ) diblock copolymer vesicles (denoted G 58 -(H 300 -stat-ERh 1 ), where m ¼ 100 and n ¼ 0) and (97 PGMA 58 + 3 PMPC 60 )-P(HPMA 300 -stat-GlyMARh 1 ) diblock copolymer vesicles (denoted (97 G 58 + 3 M 60 )-(H 300 -stat-ERh 1 )-D 52 where m ¼ 97 and n ¼ 3) via RAFT aqueous dispersion polymerization. Corresponding schematic cartoons are also shown for each type of precursor vesicle, where PGMA ¼ red, PMPC ¼ green, P(HPMA-stat-ERh 1 ) ¼ blue. RAFT endgroups are omitted from chemical structures to aid clarity.This journal is