Red blood cell (RBC) membrane-cloaked nanoparticles, reserving the intact cell membrane structure and membrane protein, can gain excellent cell-specific functions such as long blood circulation and immune escape, providing a promising therapy nanoplatform for drug delivery. Herein, a novel RBC membrane biomimetic combination therapeutic system with tumor targeting ability is constructed by embedding bovine serum albumin (BSA) encapsulated with 1,2-diaminocyclohexane-platinum (II) (DACHPt) and indocyanine green (ICG) in the targeting peptide-modified erythrocyte membrane (R-RBC@BPtI) for enhancing tumor internalization and synergetic chemophototherapy. R-RBC@BPtI displays excellent stability and high encapsulation efficiency with multiple cores enveloped in the membrane. Benefited from the stealth functionality and targeting modification of erythrocyte membranes, R-RBC@BPtI can significantly promote tumor targeting and cellular uptake. Under the near-infrared laser stimuli, R-RBC@BPtI presents remarkable instability by singlet oxygen and heat-mediated cleavage so as to trigger effective drug release, thereby achieving deep penetration and accumulation of DACHPt and ROS in the tumor site. Consequently, R-RBC@BPtI with tumor-specific targeting ability accomplishes remarkable ablation of tumors and suppressed lung metastasis in vivo by photothermal and chemotherapy combined ablation under phototriggering. This research provides a novel strategy of targeted biomimetic nanoplatforms for combined cancer chemotherapy-phototherapy.
A major challenge in siRNA vectors is developing approaches that ensure that when administered in vivo, the vectors can target their requisite site of action. This study reports a third type of nanoworm, biomimetic nanoerythrocytes for siRNA delivery, except for filomicelle and nanoworm iron‐oxide particle, which is the first approach that allows for targeted siRNA delivery by a process involving red blood cell (RBC) membrane cloaking of charge‐reversible polyplexes of siRNA and polycation. RBC membrane cloaking protects siRNA from RNase A degradation. Moreover, the RBC membrane‐cloaked charge‐reversible siRNA vector (RBC‐reversible polyplex (RP)) not only stays longer in the blood circulation than that of negatively charged bovine serum albumin (BSA) spheres and positively charged BSA, but is also able to escape from late endosomes/lysosomes, to achieve effective transfection for gene knockdown. The knockdown result in vivo is remarkably consistent with that of intracellular trafficking and transfection in vitro. Due to the outstanding biocompatibility and active targeting (cRGD), the 7 mg kg−1 dose siSurvivin in RGD‐RBC‐RP exhibits obviously superior anticancer effects at the animal level after two weeks. Therefore, the biomimetic worm‐like nanoerythrocyte charge‐reversible gene vector is a new and general method for highly efficient siRNA therapy in vivo.
A new kind of block copolymer micelles methoxy polyethylene glycol (mPEG) grafted a-zein protein (mPEG-g-a-zein) was synthesized. The chemical composition of mPEG-g-a-zein was identified with the help of FT-IR and 1 H-NMR. The biohybrid polymer can selfassemble into spherical core-shell nanoparticles in aqueous solution. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were used to investigate the self-assembled morphology of mPEG-g-a-zein. Dynamic light scattering (DLS) results showed that the particle size of mPEG-g-a-zein was about 90 nm. Moreover, the nanoparticles had a very low critical micelle concentration value with only 0.02 mg/mL. Then, the anticancer drug curcumin (CUR) was encapsulated into the biohybrid polymer micelles. The in vitro drug release profile showed a zero-order release of CUR up to 12 h at 378C. Cell viability studies revealed that the mPEG-g-a-zein polymer exhibited low cytotoxicity for HepG2 cells (human hepatoma cells). Consequently, the mPEG-g-a-zein micelles can be used as a potential nano-carrier to encapsulate hydrophobic drugs and nutrients.
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