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Islet transplantation holds significant promise as a curative approach for type 1 diabetes (T1D). However, the transition of islet transplantation from the experimental phase to widespread clinical implementation has not occurred yet. One major hurdle in this field is the challenge of insufficient vascularization and subsequent early loss of transplanted islets, especially in non-intraportal transplantation sites. The establishment of a fully functional vascular system following transplantation is crucial for the survival and secretion function of islet grafts. This vascular network not only ensures the delivery of oxygen and nutrients, but also plays a critical role in insulin release and the timely removal of metabolic waste from the grafts. This review summarizes recent advances in effective strategies to improve graft revascularization and enhance islet survival. These advancements include the local release and regulation of angiogenic factors (e.g., vascular endothelial growth factor, VEGF), co-transplantation of vascular fragments, and pre-vascularization of the graft site. These innovative approaches pave the way for the development of effective islet transplantation therapies for individuals with T1D.

Microglia‐mediated inflammation is involved in the pathogenesis of Alzheimer's disease (AD), whereas human fibroblast growth factor 21 (hFGF21) has demonstrated the ability to regulate microglia activation in Parkinson's disease, indicating a potential therapeutic role in AD. However, challenges such as aggregation, rapid inactivation, and the blood–brain barrier hinder its effectiveness in treating AD. This study develops targeted delivery of hFGF21 to activated microglia using BV2 cell membrane‐coated PEGylated liposomes (hFGF21@BCM‐LIP), preserving the bioactivity of hFGF21. In vitro, hFGF21@BCM‐LIP specifically targets Aβ1‐42‐induced BV2 cells, with uptake hindered by anti‐VCAM‐1 antibody, indicating the importance of VCAM‐1 and integrin α4/β1 interaction in targeted delivery to BV2 cells. In vivo, following subcutaneous injection near the lymph nodes of the neck, hFGF21@BCM‐LIP diffuses into lymph nodes and distributes along the meningeal lymphatic vasculature and brain parenchyma in amyloid‐beta (Aβ1‐42)‐induced mice. Furthermore, the administration of hFGF21@BCM‐LIP to activated microglia improves cognitive deficits caused by Aβ1‐42and reduces levels of tau, p‐Tau, and BACE1. It also decreases interleukin‐6  (IL‐6) and tumor necrosis factor‐α (TNF‐α) release while increasing interleukin‐10 (IL‐10) release both in vivo and in vitro. These results indicate that hFGF21@BCM‐LIP can be a promising treatment for AD, by effectively crossing the blood–brain barrier and targeting delivery to brain microglia via the neck‐meningeal lymphatic vasculature‐brain parenchyma pathways. In this study, the BV2 cell membrane‐coated PEGylated‐liposomes for hFGF21 (hFGF21@BCM‐LIP) exhibit active targeting of Aβ‐activated microglia. Following subcutaneous injection in the neck skin, hFGF21@BCM‐LIP diffuses into the lymph node and subsequently distributes along the meningeal lymphatic vasculature, thereby bypassing the blood–brain barrier. This drug system effectively inhibits neuroinflammatory responses and improves amyloid‐beta (Aβ1‐42)‐induced deficits in learning and memory.

Disulfiram (DSF) is an FDA-approved anti-alcoholic drug that has recently proven to be effective in cancer treatment. However, the short half-life in the bloodstream and the metal ion-dependent antitumor activity significantly limited the further application of DSF in the clinical field. To this end, we constructed a silk fibroin modified disulfiram/zinc oxide nanocomposites (SF/DSF@ZnO) to solubilize and stabilize DSF, and, more importantly, achieve pH triggered Zn2+release and subsequent synergistic antitumor activity. The prepared SF/DSF@ZnO nanocomposites were spherical and had a high drug loading. Triggered by the lysosomal pH, SF/DSF@ZnO could induce the rapid release of Zn2+under the acidic conditions and caused nanoparticulate disassembly along with DSF release. In vitro experiments showed that cytotoxicity of DSF could be enhanced by the presence of Zn2+, and further amplified when encapsulated into SF/DSF@ZnO nanocomposites. It was confirmed that the significantly amplified cytotoxicity of SF/DSF@ZnO was resulted from pH-triggered Zn2+release, inhibited cell migration, and increased ROS production. In vivo study showed that SF/DSF@ZnO nanocomposites significantly increased the tumor accumulation and prolonged the retention time. In vivo antitumor experiments in the xenograft model showed that SF/DSF@ZnO exerted the highest tumor-inhibition rate among all the drug treatments. Therefore, this exquisite study established silk fibroin-modified disulfiram/zinc oxide nanocomposites, SF/DSF@ZnO, where ZnO not only acted as a delivery carrier but also served as a metal ion reservoir to achieve synergistic antitumor efficacy. The established DSF nanoformulation displayed excellent therapeutic potential in future cancer treatment.

Islet transplantation has been considered the most promising therapeutic option with the potential to restore the physiological regulation of blood glucose concentrations in type 1 diabetes treatment. However, islets suffer from oxidative stress and nonspecific inflammation in the early stage of transplantation, which attributed to the leading cause of islet graft failure. Our previous study reported that bilirubin exerted antioxidative and anti-inflammatory effects on hypothermic preserved islets, which inspire us to utilize bilirubin to address the survival issue of grafted islets. However, the application of bilirubin for islet transplantation is limited by its poor solubility and fast clearance. In this study, we designed a supramolecular carrier (PLCD) that could improve the solubility of bilirubin and slowly release bilirubin to protect islets after cotransplantation. PLCD was synthesized by conjugating activated β-cyclodextrin (β-CD) to the side chain of ε-polylysine (PLL) and acted as a carrier to load bilirubin via host–guest interactions. The constructed bilirubin supramolecular system (PLCD-BR) significantly improved the solubility and prolonged the action time of bilirubin. In vitro results confirmed that PLCD-BR coculture substantially enhanced the resistance of islets to excessive oxidative stress and proinflammatory stimulation and maximumly maintained the islet function. In vivo, PLCD could prolong drug duration at the transplant site, and the localized released bilirubin could protect the islets from oxidative stress and suppress the production of inflammatory cytokines. Crucially, islet transplantation with PLCD-BR significantly extended the stable blood glucose time of diabetic mice and produced a faster glucose clearance compared to those cotransplanted with free bilirubin. Additionally, immunohistochemical analysis showed that PLCD-BR had superior antioxidative and anti-inflammatory abilities and beneficial effects on angiogenesis. These findings demonstrate that the PLCD-BR has great potentials to support successful islet transplantation.

Keratinocyte growth factor (KGF) has a good therapeutic effect on injured corneas. However, due to the washout of tears and blinking, locally administrated KGF usually has a short residence time on the surface of an injured cornea, resulting in its poor bioavailability. Herein, a bioadhesive hydrogel is described produced using cysteine-modified γ-polyglutamic acid (PGA-Cys) as the hydrogel-forming material to locally deliver KGF. A series of PGA-Cys polymers with different graft ratios of cysteine were firstly synthesized and carefully characterized. Thereafter, the PGA-Cys hydrogel was screened by changing the graft ratio of cysteine and polymer concentration, and the apparent viscosities and bioadhesive force were also carefully investigated. It was found that PGA-Cys polymers with different graft ratios of cysteine exhibited tunable apparent viscosity and bioadhesive properties at the same polymer concentration. When PGA-Cys with a graft ratio of 1.5 mmol g−1of cysteine (PGA-Cys-1.5) was used as hydrogel-forming material, the hydrogel exhibited a good gelation property with an apparent viscosity of 5.2 Pa s and strong bioadhesive force of 167 ± 0.5 mN. In vitrorelease study showed that KGF was slowly released from PGA-Cys-1.5 hydrogel over a longer time in comparison to PGA solution alone. Moreover, PGA-Cys-1.5 hydrogel enabled most of the encapsulated KGF to be retained on the cornea and conjunctiva after local administration. Meanwhile, the morphology of the corneal epithelium in the alkali-injured cornea of mice was well repaired after 7 days of treatment with KGF-PGA-Cys-1.5 hydrogel. The therapeutic mechanism was strongly associated with inhibiting corneal inflammation and neovascularization, promoting proliferation of the corneal epithelium and inhibiting apoptosis. Overall, the use of the bioadhesive PGA-Cys hydrogel with a suitable KGF release profile may be a more promising approach than using PGA solution alone and KGF to repair injured corneas.

Currently, phototherapy initiated by local irradiation with a near-infrared (NIR) laser has emerged as a promising strategy for cancer treatment owing to its low toxicity. However, a key problem for effective phototherapy is how to specifically deliver a sufficient dose of photosensitizers to a tumor focus. Herein, indocyanine green (ICG), a United States Food and Drug Administration (US FDA)-approved photosensitizer, was first encapsulated in an inner aqueous compartment of liposome (ICG-LIP) to improve its stability. Thereafter, tumor cell membranes were isolated from native glioma cells and subsequently inlaid in the bilayer lipid membrane of ICG-LIP to construct cell-like liposomes (ICG-MCLs). ICG was easily encapsulated into the ICG-MCLs with a very high encapsulation efficiency, reaching 78.01 ± 0.72% and its concentration in the final formulation reached 200 μg mL−1. The ICG-MCLs displayed a spherical morphology with a hydrodynamic diameter (Dh) of 115.0 ± 0.5 nm, a PDI of 0.14, and a zeta potential of −11.2 ± 0.9 mV. Moreover, ICG-MCLs exhibited a good stability in terms of particle size and significantly improved the chemical stability of ICG in pH 7.4 PBS at 37 °C. In addition, the temperature of the ICG-MCLs rapidly increased to 63 °C after 10 min irradiation and this was maintained for a longer time. Owing to the cancer cell membrane associated protein, the ICG-MCLs were specifically internalized by homogenous glioma C6 cells in vitro, which resulted in the strong red fluorescence of ICG in cytoplasm. Moreover, in vivoimaging showed that the ICG-MCLs were effectively homed to the tumor site of C6 glioma-bearing Xenograft nude mice through vein injection, which resulted in the temperature of the tumor site rapidly rising, allowing the killing of tumor cells after local NIR irradiation. After treatment with the ICG-MCLs, the primary tumor focus was completely eradicated and lung metastases were effectively inhibited. In conclusion, liposomes inlaid with tumor cellular membranes may serve as an excellent nanoplatform for homologous-targeting phototherapy using ICG.

Hydrogel was not only used as an effective support matrix to prevent intrauterine adhesion after endometrial injury but also served as scaffold to sustain release of some therapeutics, especially growth factor. However, because of the rapid turnover of the endometrial mucus, the poor retention and bad absorption of therapeutic agents in damaged endometrial cavity were two important factors hindering their pharmacologic effect. Herein, a mucoadhesive hydrogel was described by using heparin-modified poloxamer (HP) as the matrix material and ε-polylysine (EPL) as functional excipient. Various EPL-HP hydrogels formulations are screened by rheological evaluation and mucoadhesion studies. It was found that the rheological and mucoadhesive properties of EPL-HP hydrogels were easily controlled by changing the amount of EPL in formulation. The storage modulus of EPL-HP hydrogel with 90 μg/mL of EPL (EPL-HP-90) was elevated to be 1.9 × 105Pa, in accordance with the adhesion force rising to 3.18 N (10-fold higher than HP hydrogels). Moreover, in vitro release of model drug keratinocyte growth factor (KGF) from EPL-HP hydrogel was significantly accelerated by adding EPL in comparison with HP hydrogel. Both strong mucoadhesive ability and the accelerated drug release behavior for EPL-HP-90 made more of the encapsulated KGF absorbed by the uterus basal layer and endometrial glands after 8 h of administration in uterus cavity. Meanwhile, the morphology of endometrium in the injured uterus was repaired well after 3 d of treatment with KGF-EPL-HP-90 hydrogels. Compared with KGF-HP group, not only proliferation of endometrial epithelial cell and glands but also angiogenesis in the regenerated endometrium was obviously enhanced after treatment with KGF-EPL-HP-90 hydrogels. Alternatively, the cellular apoptosis in the damaged endometrium was significantly inhibited after treatment with KGF-EPL-HP-90 hydrogels. Overall, the mucoadhesive EPL-HP hydrogel with a suitable KGF release profile may be a more promising approach than HP hydrogel alone to repair the injured endometrium.

Introduction:Though many agents have therapeutic potentials for brain diseases, few have been used in clinical environments because of the brain barriers. As an effective interventional technique, ultrasound (US) could be a potentially feasible approach to disrupt the blood-brain barrier (BBB) and deliver therapeutic agents into the brain.Areas covered:This article reviews up-to-date ultrasound-mediated strategies in opening the brain barriers for drug brain delivery. The mechanisms and problems of these approaches are discussed, as well as the challenges and potentials associated with the ultrasound-mediated strategies that are currently available or under development.Expert opinion:Despite recent successes in opening the blood brain barrier (BBB) via microbubble-enhanced focused ultrasound, the exact mechanisms of how the barrier is disrupted, remains unknown. A complete understanding of the mechanisms involved in the ultrasound-mediated disruption of the BBB and improving the efficiency of drug delivery to targeted brain regions can greatly facilitate the successful development and translation of the technology.

KPV (Lys–Pro–Val), which is a tripeptide derived from α-MSH (α-melanocyte-stimulating hormone), has an anti-inflammatory effect on colitis. However, KPV solution is very unstable when rectally administered, compromising its therapeutic efficacy. Herein, cysteamine-grafted γ-polyglutamic acid (SH-PGA) was synthesized by conjugating cysteamine with the carboxyl groups of γ-PGA. The synthesized SH-PGA has the thiol grafting amount of 4.5 ± 0.3 mmol/g. Without the use of the cross-linker, the SH-PGA hydrogel with 4% of the polymer was formed by self-cross-linking of thiol groups. Moreover, the formation of the SH-PGA hydrogel was not affected by KPV. The KPV/SH-PGA hydrogel presented higher elastic modulus (G′) than the corresponding viscous modulus (G″) at 0.01–10 Hz, exhibiting good mechanical stability. The KPV/SH-PGA hydrogel presented a shear-thinning behavior, which was helpful for rectal administration. Only 30% of KPV was released from the KPV/SH-PGA hydrogel within 20 min, followed by a sustained-release behavior. Importantly, the stability of KPV in the SH-PGA hydrogel was obviously enhanced, which was presented by detecting its anti-inflammatory activity and promoting cell migration potential after 2 h of exposure to 37 °C. The enhanced therapeutic effect of the KPV/SH-PGA hydrogel on colitis was confirmed on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis rats. The colitis symptoms including body weight loss and the disease activity index score were obviously attenuated by rectally administering the KPV/SH-PGA hydrogel. Besides, the KPV/SH-PGA hydrogel treatment prevented the colon shortening of TNBS-infused rats and decreased the colonic myeloperoxidase level. The morphology of the colon including the epithelial barrier, crypt, and intact goblet cells was recovered after KPV/SH-PGA hydrogel treatment. Besides, the KPV/SH-PGA hydrogel decreased the expression of proinflammatory cytokines such as tumor necrosis factor α and interleukin 6. Collectively, the KPV/SH-PGA hydrogel may provide a promising strategy for the treatment of ulcerative colitis.

Herein, a theranostic liposome (QSC‐Lip) integrated with superparamagnetic iron oxide nanoparticles (SPIONs) and quantum dots (QDs) and cilengitide (CGT) into one platform is constructed to target glioma under magnetic targeting (MT) for guiding surgical resection of glioma. Transmission electron microscopy and X‐ray photoelectron spectroscopy confirm the complete coencapsulation of SPIONs and QDs in liposome. Besides, CGT is also effectively encapsulated into the liposome with an encapsulation efficiency of ∼88.9%. QSC‐Lip exhibits a diameter of 100 ± 1.24 nm, zeta potential of −17.10 ± 0.11 mV, and good stability in several mediums. Moreover, each cargo shows a biphasic release pattern from QSC‐Lip, a rapid initial release within initial 10 h followed by a sustained release. Cellular uptake of QSC‐Lip is significantly enhanced by C6cells under MT. In vivo dual‐imaging studies show that QSC‐Lip not only produces an obvious negative‐contrast enhancement effect on glioma by magnetic resonance imaging but also makes tumor emitting fluorescence under MT. The dual‐imaging of QSC‐Lip guides the accurate resection of glioma by surgery. Besides, CGT is also specifically distributed to glioma after administration of QSC‐Lip under MT, resulting in an effective inhibition of tumors. The integrated liposome may be a potential carrier for theranostics of tumor. The accurate imaging of tumor marginsis pivotal for the complete surgical resection of glioma. In this study, a theranostic liposome (QSC‐Lip) is constructed to target glioma under an exogenous magnetic field (magnetic targeting) for magnetic resonance imaging and fluorescence imaging. The dual‐imaging ability of QSC‐Lip has successfully guided the accurate resection of glioma by surgery.

How to maintain the stability of basic fibroblast growth factor (bFGF) in wounds with massive wound fluids is important to accelerate wound healing. Here, a novel liposome with hydrogel core of silk fibroin (SF‐LIP) is successfully developed by the common liposomal template, followed by gelation of liquid SF inside vesicle under sonication. SF‐LIP is capable of encapsulating bFGF (SF‐bFGF‐LIP) with high efficiency, having a diameter of 99.8 ± 0.5 nm and zeta potential of −9.41 ± 0.10 mV. SF‐LIP effectively improves the stability of bFGF in wound fluids. After 8 h of incubation with wound fluids at 37 °C, more than 50% of free bFGF are degraded, while only 18.6% of the encapsulated bFGF in SF‐LIP are destroyed. Even after 3 d of preincubation with wound fluids, the cell proliferation activity and wound healing ability of SF‐bFGF‐LIP are still preserved but these are severely compromised for the conventional bFGF‐liposome (bFGF‐LIP). In vivo experiments reveal that SF‐bFGF‐LIP accelerates the wound closure of mice with deep second‐degree scald. Moreover, due to the protective effect and enhanced penetration ability, SF‐bFGF‐LIP is very helpful to induce regeneration of vascular vessel in comparison with free bFGF or bFGF‐LIP. The liposome with SF hydrogel core may be a potential carrier as growth factors for wound healing. Maintaining the stability of basic fibroblast growth factor (bFGF) in wound fluidsis important to accelerate wound healing. In this study, a novel liposome (LIP) with silk fibroin (SF) hydrogel core has been proposed as an innovative carrier of bFGF for deep second‐degree scald. Due to the protective effect and enhanced penetration ability, SF‐bFGF‐LIP exhibits a better wound healing effect than free bFGF or the common bFGF‐liposome.