We report the construction of erythrocyte membrane-cloaked Janus polymeric motors (EM-JPMs) which are propelled by near-infrared (NIR) laser irradiation and are successfully applied in thrombus ablation. Chitosan (a natural polysaccharide with positive charge, CHI) and heparin (glycosaminoglycan with negative charge, Hep) were selected as wall materials to construct biodegradable and biocompatible capsules through the layer-by-layer self-assembly technique. By partially coating the capsule with a gold (Au) layer through sputter coating, a NIR-responsive Janus structure was obtained. Due to the asymmetric distribution of Au, a local thermal gradient was generated upon NIR irradiation, resulting in the movement of the JPMs through the self-thermophoresis effect. The reversible “on/off” motion of the JPMs and their motile behavior were easily tuned by the incident NIR laser intensity. After biointerfacing the Janus capsules with an erythrocyte membrane, the EM-JPMs displayed red blood cell related properties, which enabled them to move efficiently in relevant biological environments (cell culture, serum, and blood). Furthermore, this therapeutic platform exhibited excellent performance in ablation of thrombus through photothermal therapy. As man-made micromotors, these biohybrid EM-JPMs hold great promise of navigating in vivo for active delivery while overcoming the drawbacks of existing synthetic therapeutic platforms. We expect that this biohybrid motor has considerable potential to be widely used in the biomedical field.

c-CLEnA are obtained via cross-linking enzymes in the nanocavity of supramolecular stomatocytes. Such c-CLEnA can be recycled while retaining its activity – an excellent nanoreactors platform for in-flow bio-catalysis.

Medicine formulations at the nanoscale, referred to as nanomedicines, have managed to overcome key challenges encountered during the development of new medical treatments and entered clinical practice, but considerable improvement in terms of local efficacy and reduced toxicity still need to be achieved. Currently, the fourth-generation of nanomedicines is being developed, employing biocompatible nanocarriers that are targeted, multifunctional, and stimuli-responsive. Proteins and polypeptides can fit the standards of an efficient nanovector because of their biodegradability, intrinsic bioactivity, chemical reactivity, stimuliresponsiveness, and ability to participate in complex supramolecular assemblies. These biomacromolecules can be obtained from natural resources, produced in heterologous hosts, or chemically synthesized, allowing for different designs to access suitable carriers for a variety of drugs. To enhance targeting or therapeutic functionality, additional chemical modifications can be applied. This review demonstrates the potential of polypeptide and protein materials for the design of drug delivery nanocarriers with a special focus on their preclinical evaluation in vitro and in vivo.

Two pairs of oppositely charged PEO-b-poly(amino acid) copolymers with neutral poly(ethylene oxide) block and polypeptide block composed of the hydrophobic L-phenylalanine (Phe) amino acid mixed with either negative L-glutamic acid (Glu) or positive L-lysine (Lys) units were synthesized. N-carboxyanhydride (NCA) ring opening polymerization (ROP) was performed with either PEO46-NH2 or PEO114-NH2 macroinitiators, leading respectively to PEO46b-P(Glu100-co-Phe65) and PEO46-b-P(Lys100-co-Phe65), and PEO114-b-P(Glu60-co-Phe40) and PEO114-b-P(Lys60-co-Phe40). Polyion complexes (PIC) formed at near charge equilibrium led to vesicle formation (PICsomes), as shown by DLS, zetametry and TEM. The good stability of PICsomes, even in high salinity media, was interpreted by π-π stacking hydrophobic interactions between the Phe residues, playing the role of "physical cross-linking". These PICsomes were successfully loaded with siRNA directed against firefly luciferase enzyme expression. They also exhibit minimal cell cytotoxicity while superior silencing efficacy was shown by cell bioluminescence assay as compared to free siRNA and a standard lipofectamine-siRNA complex. As such, self-assembly of oppositely charged PEO-b-poly(amino acids) block copolymers enabled forming PICsomes of high stability thanks to π-π interactions of the Phe comonomer in the polypeptide block, with high potential as biocompatible nanocarriers for RNA interference.

In this study a histidine containing elastin‐like polypeptide (ELP) diblock copolymer is described with multiresponsive assembly behavior. Self‐assembly into micelles is examined by two methods. First, the self‐assembly is triggered by the addition of divalent metal ions, with Zn2+ being the most suitable one. Increasing the Zn2+ concentration stabilizes the nanoparticles over a large temperature window (4–45 °C). This diblock exhibits furthermore pH‐responsiveness, and particles disassemble under mildly acidic conditions. Second, the coassembly of this ELP with a diblock ELP is examined, which is not responsive to pH and metal ions. Coassembly is triggered by heating the ELPs quickly above the transition temperature of the less hydrophobic block, which results in stable nanoparticles without the need to add metal ions. This novel ELP system offers a versatile modular nanocarrier platform that can respond to different stimuli and can be tuned effectively.