Synthesis of Artificial Membrane of Copolymer (Acrylic Acid/Butyl Acrylate) PAA-PBA for the Design of Polymersomes

Polymersomes are synthetic vesicles that imitate biological membrane functions. The purpose of this work is to develop an artificial copolymer (acrylic acid/butyl acrylate) PAA-PBA membrane by random synthesis. A factorial design 2^k was applied to determine the conditions for this reaction. The Fourier transform infrared spectrometer indicated that the polymerization reaction was complete without a –C=C-absorption peak. The Gordon-Taylor equation showed that the hydrophilic part of the PAA-PBA composition is 20–40% and the hydrophobic part 60–80%. The authors selected the copolymers with low molecular weight, within the range of 3134.49 ± 994.21 g/mol and a polydispersity of 1.40.     

Preparation of Functionalized Polymersomes and the In Vivo Imaging

Recently, polymersomes self-assembled from amphiphilic block copolymers have attracted considerable interests with superior physicochemical properties. Here, the biotinylated block copolymers were blended with unmodified block copolymers to produce biotinylated polymersomes via film rehydration. Then, the avidin molecules were attached onto the biotin molecules covalently linked with block copolymers to form surface functionalized vesicles that are capable of carrying various biotinylated bioactive molecules, generating a relatively universal delivery platform. Hydrophobic fluorophores DAF and Nile Red were encapsulated respectively into hydrophobic membrane to prepare hydrophobic substances loaded polymersomes for investigating the nature of hydrophobic functionalization. Furthermore, the hydrophobic functionalized DiR-polymersomes were employed to perform in vivo imaging to survey the in vivo behavior for nano-polymersomes with hydrophobic functionalization.     

A Generalized System for Photo-Responsive Membrane Rupture in Polymersomes

Polymersomes are vesicles whose membranes are comprised of self-assembled block co-polymers. We recently showed that co-encapsulating conjugated multi-porphyrin dyes in a polymersome membrane with ferritin protein in the aqueous lumen confers photo-lability to the polymersome. In the present study, we illustrate that the photo-lability can be extended to vesicles containing dextran, an inert and inexpensive polysaccharide, as the luminal solute. Here we explore how structural features of the polymersome/porphyrin/dextran composite affect its photo-response. Increasing dextran molecular weight, decreasing block copolymer molecular weight, and altering fluorophore-membrane interactions results in increasing the photo-responsiveness of the polymersomes. Amphiphilic interactions of the luminal encapsulant with the membrane coupled with localized heat production in the hydrophobic bilayer likely cause differential thermal expansion in the membrane and the subsequent membrane rupture. This study suggests a general approach to impart photo-responsiveness to any biomimetic vesicle system without chemical modification, as well as a simple, bio-inert method for constructing photo-sensitive carriers for controlled release of encapsulants.     

Light‐Driven Proton Transfer for Cyclic and Temporal Switching of Enzymatic Nanoreactors

Temporal activation of biological processes by visible light and subsequent return to an inactive state in the absence of light is an essential characteristic of photoreceptor cells. Inspired by these phenomena, light‐responsive materials are very attractive due to the high spatiotemporal control of light irradiation, with light being able to precisely orchestrate processes repeatedly over many cycles. Herein, it is reported that light‐driven proton transfer triggered by a merocyanine‐based photoacid can be used to modulate the permeability of pH‐responsive polymersomes through cyclic, temporally controlled protonation and deprotonation of the polymersome membrane. The membranes can undergo repeated light‐driven swelling–contraction cycles without losing functional effectiveness. When applied to enzyme loaded‐nanoreactors, this membrane responsiveness is used for the reversible control of enzymatic reactions. This combination of the merocyanine‐based photoacid and pH‐switchable nanoreactors results in rapidly responding and versatile supramolecular systems successfully used to switch enzymatic reactions ON and OFF on demand.     

Advancements and Challenges in Multidomain Multicargo Delivery Vehicles

Reparative and regenerative processes are well‐orchestrated temporal and spatial events that are governed by multiple cells, molecules, signaling pathways, and interactions thereof. Yet again, currently available implantable devices fail largely to recapitulate nature's complexity and sophistication in this regard. Herein, success stories and challenges in the field of layer‐by‐layer, composite, self‐assembly, and core–shell technologies are discussed for the development of multidomain/multicargo delivery vehicles.     

Protein Toxin Chaperoned by LRP‐1‐Targeted Virus‐Mimicking Vesicles Induces High‐Efficiency Glioblastoma Therapy In Vivo

Glioblastoma is a most intractable and high‐mortality malignancy because of its extremely low drug accessibility resulting from the blood–brain barrier (BBB). Here, it is reported that angiopep‐2‐directed and redox‐responsive virus‐mimicking polymersomes (ANG‐PS) (angiopep‐2 is a peptide targeting to low‐density lipoprotein receptor‐related protein‐1 (LRP‐1)) can efficiently and selectively chaperone saporin (SAP), a highly potent natural protein toxin, to orthotopic human glioblastoma xenografts in nude mice. Unlike chemotherapeutics, free SAP has a low cytotoxicity. SAP‐loaded ANG‐PS displays, however, a striking antitumor activity (half‐maximal inhibitory concentration, IC₅₀ = 30.2 × 10^?9m ) toward U‐87 MG human glioblastoma cells in vitro as well as high BBB transcytosis and glioblastoma accumulation in vivo. The systemic administration of SAP‐loaded ANG‐PS to U‐87 MG orthotopic human‐glioblastoma‐bearing mice brings about little side effects, effective tumor inhibition, and significantly improved survival rate. The protein toxins chaperoned by LRP‐1‐targeted virus‐mimicking vesicles emerge as a novel and highly promising treatment modality for glioblastoma.