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Natural cells have been explored as drug carriers for a long period. They have received growing interest as a promising drug delivery system (DDS) until recently along with the development of biology and medical science. The synthetic materials, either organic or inorganic, are found to be with more or less immunogenicity and/or toxicity. The cells and extracellular vesicles (EVs), are endogenous and thought to be much safer and friendlier. Furthermore, in view of their host attributes, they may achieve different biological effects and/or targeting specificity, which can meet the needs of personalized medicine as the next generation of DDS. In this review, we summarized the recent progress in cell or cell membrane-based DDS and their fabrication processes, unique properties and applications, including the whole cells, EVs and cell membrane coated nanoparticles. We expect the continuing development of this cell or cell membrane-based DDS will promote their clinic applications.

Cancer immunotherapy is mainly focused on manipulating patient's own immune system to recognize and destroy cancer cells. Vaccine formulations based on nanotechnology have been developed to target delivery antigens to antigen presenting cells (APCs), especially dendritic cells (DCs) for efficiently induction of antigen-specific T cells response. To enhance DC targeting and antigen presenting efficiency, we developed erythrocyte membrane-enveloped poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles for antigenic peptide (hgp10025-33) and toll-like receptor 4 agonist, monophosphoryl lipid (MPLA). A Mannose-inserted membrane structure was constructed to actively target APCs in the lymphatic organ, and redox-sensitive peptide-conjugated PLGA nanoparticles were fabricated which prone to cleave in the intracellular milieu. The nanovaccine demonstrated the retained protein content in erythrocyte and enhanced in vitro cell uptake. An antigen-depot effect was observed in the administration site with promoted retention in draining lymph nodes. Compared with other formulations after intradermal injection, the nanovaccine prolonged tumor-occurring time, inhibited tumor growth, and suppressed tumor metastasis in prophylactic, therapeutic, and metastatic melanoma models, respectively. Additionally, we revealed that nanovaccine effectively enhanced IFN-γ secretion and CD8(+) T cell response. Taken together, these results demonstrated the great potential in applying an erythrocyte membrane-enveloped polymeric nanoplatform for an antigen delivery system in cancer immunotherapy.

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The discrete coordination-driven self assemblies have received continuous attention due to their molecular architecture esthetics and applications in recognition, catalysis, storage, etc. [ 1 ] Among these self assemblies, one species that has emerged recently is the porous coordination nanocages formed between carboxylate ligands and metal clusters, which are also known as metal-organic polyhedra (MOP). [ 2 ] Due to the robust porous structure and versatile functionality, they have found applications as plasticizer, gas sponge, ion channel, coatings, and building units. [ 3 ] Presumably, the porous shell and uniform yet tunable cavity make them good candidates for drug delivery purpose. However, almost all the coordination nanocages reported so far are hydrophobic, which greatly limits their applications in aqueous condition. We hypothesize this problem can be circumvented by turning these nanocages into colloids through surface functionalization with hydrophilic polymers. In this Communication, we report a porous coordination nanocage covered with alkyne groups and its surface functionalization by grafting with azide-terminated polyethylene glycol (PEG) through "click chemistry". In addition, its drug load and release capacity has been evaluated using an anticancer drug 5-fl uorouracil as a model.The metal-organic cuboctahedron was chosen as the prototype of nanocage in this study. [ 2a , 2c ] It is composed of 12 dicopper paddlewheel clusters and 24 isophthalate moieties, with 8 triangular and 6 square windows that are roughly 8 and 12 Å across, respectively. The internal cavity has a diameter of around 15 Å. The 5-position of isophthalate moieties would be the reaction site for surface functionalization. The Cu(I)-catalyzed Huisgen cycloaddition between azide and alkyne, a so-called "click reaction", was chosen as the synthetic tool in this study due to its high yield, mild reaction condition, and easy operation. [ 4 ] Based on the retrosynthetic analysis and the convenience of implementation, alkyne-covered nanocage and azide-terminated PEG are two prerequisites. The synthesis and characterization of alkyne-covered metal-organic cuboctahedron is not as straightforward as it seems to be. Since NMR signal would be elusive due to the presence of paramagnetic Cu(II) in these nanocages, [ 5 ] single crystal X-ray diffraction might be the only characterization tool available. Therefore, obtaining a single crystal of the nanocage would be of paramount importance for characterization. Figure 1a illustrates all the ligand precursors we've tried in synthesizing this "clickable" nanocage, which comprise isophthalate moiety capable of forming metalorganic cuboctahedron and alkyne group suitable for click reaction. Solvothermal reaction, a process involving heating the ligand/metal mixture solution within sealed environment at high temperature, is often used in synthesizing these coordination nanocages. [ 2a ] The solvothermal reaction between 5-ethynylisophthalic acid (H 2 ei) and copper salt ended up with a coordin...