Surface engineering of nanomaterials with phospholipid-polyethylene glycol-derived functional conjugates for molecular imaging and targeted therapy.

In recent years, phospholipid-polyethylene glycol-derived functional conjugates have been widely employed to decorate different nanomaterials, due to their excellent biocompatibility, long blood circulation characteristics, and specific targeting capability. Numerous in vivo studies have demonstrated that nanomedicines peripherally engineered with phospholipid-polyethylene glycol-derived functional conjugates show significantly increased selective and efficient internalization by target cells/tissues. Targeting moieties including small-molecule ligands, peptides, proteins, and antibodies are generally conjugated onto PEGylated phospholipids to decorate liposomes, micelles, hybrid nanoparticles, nanocomplexes, and nanoemulsions for targeted delivery of diagnostic and therapeutic agents to diseased sites. In this review, the synthesis methods of phospholipid-polyethylene glycol-derived functional conjugates, biophysicochemical properties of nanomedicines decorated with these conjugates, factors dominating their targeting efficiency, as well as their applications for in vivo molecular imaging and targeted therapy were summarized and discussed.

Approaches for the synthesis of o-nitrobenzyl and coumarin linkers for use in photocleavable biomaterials and bioconjugates and their biomedical applications.

Photocleavable biomaterials and bioconjugates are particularly interesting because light sources are easy to obtain and the responsiveness of materials is convenient to control. In recent years, various photocleavable biomaterials and bioconjugates have been synthesized for the control of payload release, regulation of biomolecule activity, 3D cell culture, and investigation of molecular mechanisms. Photocleavable linkers are crucial components of photocleavable biomaterials, which significantly influence the photoresponsive capabilities of materials. Photosensitive molecules, such as o-nitrobenzyls and coumarins, have been extensively developed as photocleavable linkers. In the present review, we provide comprehensive knowledge regarding the synthetic strategies of o-nitrobenzyl and coumarin derived linkers with various functional groups and their applications for the construction of photocleavable biomaterials and bioconjugates. Finally, the biomedical applications of o-nitrobenzyl and coumarin-based photocleavable biomaterials and bioconjugates will be summarized and discussed.

A self-illuminating nanoparticle for inflammation imaging and cancer therapy.

Nanoparticles have been extensively used for inflammation imaging and photodynamic therapy of cancer. However, the major translational barriers to most nanoparticle-based imaging and therapy applications are the limited depth of tissue penetration, inevitable requirement of external irradiation, and poor biocompatibility of the nanoparticles. To overcome these critical limitations, we synthesized a sensitive, specific, biodegradable luminescent nanoparticle that is self-assembled from an amphiphilic polymeric conjugate with a luminescent donor (luminol) and a fluorescent acceptor [chlorin e6 (Ce6)] for in vivo luminescence imaging and photodynamic therapy in deep tissues. Mechanistically, reactive oxygen species (ROS) and myeloperoxidase generated in inflammatory sites or the tumor microenvironment trigger bioluminescence resonance energy transfer and the production of singlet oxygen (1O2) from the nanoparticle, enabling in vivo imaging and cancer therapy, respectively. This self-illuminating nanoparticle shows an excellent in vivo imaging capability with suitable tissue penetration and resolution in diverse animal models of inflammation. It is also proven to be a selective, potent, and safe antitumor nanomedicine that specifically kills cancer cells via in situ 1O2 produced in the tumor microenvironment, which contains a high level of ROS.

Nanomaterial-dependent immunoregulation of dendritic cells and its effects on biological activities of contraceptive nanovaccines.

Nanovehicles are promising delivery systems for various vaccines. Nevertheless, different biophysicochemical properties of nanoparticles (NPs), dominating their in vitro and in vivo performances for vaccination, remain unclear. We attempted to elucidate the effects of NPs and their pH-sensitivity on in vitro and in vivo efficacy of resulting prophylactic nanovaccines containing a contraceptive peptide (FSHR). To this end, pH-responsive and non-responsive nanovaccines were produced using acetalated ß-cyclodextrin (Ac-bCD) and poly(lactic-co-glycolic acid) (PLGA), respectively. Meanwhile, FSHR derived from an epitope of the follicle-stimulating hormone receptor was used as the model antigen. FSHR-containing Ac-bCD and PLGA NPs were successfully prepared by a nanoemulsion technique, leading to well-shaped nanovaccines with high loading efficiency. The pH-sensitivity of Ac-bCD and PLGA nanovaccines was examined by in vitro hydrolysis and antigen release studies. Nanovaccines could be effectively engulfed by dendritic cells (DCs) via endocytosis in both dose and time dependent manners, and their intracellular trafficking was closely related to the pH-sensitivity of the carrier materials. Furthermore, nanovaccines could induce the secretion of inflammatory cytokines by DCs and T cells co-cultured with the stimulated DCs. In vivo evaluations demonstrated that nanovaccines were more potent than that based on the complete Freund's adjuvant, with respect to inducing anti-FSHR antibody, reducing the sperm count, inhibiting the sperm motility, and increasing the teratosperm rate. Immunization of male mice with nanovaccines notably decreased the parturition incidence of the mated females. Consequently, both in vitro and in vivo activities of FSHR could be considerably augmented by NPs. More importantly, our studies indicated that the pH-responsive nanovaccine was not superior over the non-responsive counterpart for the examined peptide antigen.

Engineering of Biocompatible pH-Responsive Nanovehicles from Acetalated Cyclodextrins as Effective Delivery Systems for Tumor Therapy.

There is still an unmet demand for materials with excellent biocompatibility, controlled hydrolytic capability, and elegant responsiveness to chemical or physical stimuli. To engineer biocompatible materials from ß-cyclodextrin (ß-CD), in this study, we synthesized acetalated ß-CDs (Ac-ßCDs) by one-pot acetalation using 2-ethoxypropene as an acetonation reagent, which can be further processed into nanoparticles (NPs) via the emulsion technique. Ac-ßCD NPs showed pH-labile hydrolysis and pH-triggered release of docetaxel (DTX) payload. Both properties were mainly dominated by the molar ratio of linear to cyclic acetal, which can be conveniently modulated by the acetalation time used for materials synthesis. Ac-ßCD NPs were found to be biocompatible in both in vitro cell culture and in vivo acute toxicity evaluations following intravenous injection. In vitro cell culture experiments demonstrated that antitumor activity of DTX against both sensitive and resistant cancer cells was remarkably improved by formulation into Ac-ßCD nanomedicines. In vivo antitumor study also substantiated the dramatically enhanced efficacy of DTX/Ac-ßCD NPs in a melanoma-bearing nude mouse model. These studies demonstrated that NPs derived from Ac-ßCDs may serve as biocompatible and effective carriers for drug delivery.

Biocompatible reactive oxygen species (ROS)-responsive nanoparticles as superior drug delivery vehicles.

A novel reactive oxygen species (ROS)-responsive nanoplatform can be successfully manufactured from a ROS-triggerable ß-cyclodextrin material. Extensive in vitro and in vivo studies validate that this nanoscaled system may serve as a new drug delivery vehicle with well-defined ROS-sensitivity and superior biocompatibility. This nanocarrier can be used for ROS-triggered transport of diverse therapeutics and imaging agents.