pH responsive biohybrid BSA-poly(DPA) nanoparticles for interlysosomal drug delivery

pH-responsive nanocarrier systems exhibit diverse applications due to their relevance to biological systems where, discrete pH differences are displayed between tissues and cellular compartments. Changes in the physicochemical properties of responsive nanocarriers due to variations in pH, can cause release of their cargos in a targeted and controllable manner offering spatiotemporal control. In this study, bovine serum albumin-poly(2-(diisopropylamino)ethyl methacrylate) (BSA-poly(DPA)) biohybrid nanoparticles were synthesized via controlled radical polymerization and found to be stable in neutral pH (7.4) while, at lower pHs (4–5.5) they were shown to disassemble and release their payload. In vitro tests demonstrated low cytotoxicity and energy-, dose- and time-depended internalization. BSA-poly(DPA) nanocarriers loaded with the metachromatic dye acridine orange, were successfully delivered in HeLa cells where, a pH-triggered release of their cargo into lysosomes was evidenced paving the way for applications related with the treatment of lysosomal diseases. Schematic representation of the proposed model of action of the pH sensitive, BSA-poly(DPA) nanocariers. When BSA-poly(DPA)-fluorescein nanoparticles are actively internalized, their presence in endosomes creates a punctuated pattern of green areas while green fluorescence is also detected inside lysosomes. BSA-poly(DPA) NPs loaded with acridine orange (AO) appear green in the membranes and the in endosomes since the dye is encapsulated in its monomeric form. However, when BSA-poly(DPA)-AO NPs reach the acidic environment of the lysosomes, they disassemble and release AO which is protonated and creates stacks that emit red fluorescence hence, green endosomes and few larger red lysosomes have been imaged. [Display omitted] •Protein-polymer biohybrid nanoparticles can act as pH sensitive nanocarriers for drug delivery.•BSA corona acts as a noncytotoxic agent, and offers a stealth effect, prolonging blood circulation time.•Stealth biohybrid nanocarriers release their cargos in a targeted and controllable manner.•pH sensitive, hybrid nanoparticles can be used for interlysosomal release of drugs for therapeutic applications.•Smart use of nanocarriers for enzymes could replace therapy to treat lysosomal storage disorders.