Abstract Efficient antigen delivery to antigen-presenting cells remains a critical challenge in cancer nanovaccine development. In this study, we develop a dendrimer-based nanovaccine (DenV) for efficient tumor treatment and prevention via a red blood cell (RBC) hitchhiking strategy. Utilizing phenylboronic acid-grafted dendrimers, model antigen ovalbumin (OVA) and immune adjuvant CpG oligodeoxynucleotide (CpG ODN) can be efficiently co-loaded to get DenV with a relatively simple fabrication process. Upon further RBC anchoring, DenV@RBC demonstrates a distinct application feature from DenV with a desired delivery profile to lymphoid organs. In vivo antitumor results in a mouse subcutaneous melanoma model show that both DenV and DenV@RBC achieve excellent antitumor effects following systemic administration, where the therapeutic efficacy of DenV@RBC is slightly superior to that of DenV. Meanwhile, DenV and DenV@RBC allow excellent tumor-preventive effects, regardless of local or systematic administration routes. It is also found that DenV is more robust upon local injection, while DenV@RBC yields better tumor prevention performance when administered systemically via the bloodstream. Our study offers a dendrimer-based strategy with interaction to natural RBCs for the development of highly efficient nanovaccines and holds substantial application potential in the field of cancer immunotherapy.
Abstract Silk-based materials are regarded as promising biomaterials. However, the simultaneous improvement of robustness and bioactivity remains a challenge for regenerated silk fibroin (SF). Herein, copper ion-coordinated SF (Cu@SF) films were fabricated via a one-step strategy, where Cu2+ coordination triggered the modulation of the SF aggregation structure. Cu2+ effectively modulates the aggregation structure of SF, which preserves intrinsic β-sheet nanocrystals (∼ 39%) and reinforces amorphous domains through coordination bonding. Benefiting from the reconstruction of amorphous domains triggered by Cu2+ coordination, the Cu@SF films exhibit enhanced toughness (25.62 MJ m−3). Also, the retained nanocrystal-confined amorphous network structure of Cu@SF results in a labyrinth effect when coated on magnesium, realizing anticorrosion robustness. Further, the dynamic coordination regulates Cu2+ release behavior, endowing the Cu@SF with efficient antibacterial activity (over 98% for E. coli and S. aureus) and favorable osteogenic bioactivity. This work provides a facile strategy for the rational design of robust and multifunctional silk-based biomaterials.
Abstract Fluorine-19 magnetic resonance imaging (19F MRI) offers low-background, concentration-responsive imaging but suffers from low sensitivity and short transverse relaxation times. Aggregation-induced emission (AIE) fluorophores provide complementary optical imaging through strong fluorescence upon aggregation. Here, fluorinated amphiphilic block copolymers were prepared by reversible addition−fragmentation chain-transfer (RAFT) polymerization of dimethylaminoethyl methacrylate (DMAEMA) and tetraphenylethylene acrylate (TPEA), followed by phosphocholine fluorination. The resulting PTPE-PFCP nanoparticles self-assembled into core−shell structures with a hydrophobic AIE-active PTPE core and a hydrophilic fluorinated phosphocholine corona. The optimized nanoparticles showed well-resolved 19F signals, with T1 and T2 values of 0.222 and 0.184 s, respectively, and gave readily detectable 19F MRI signals. Fluorescence increased over 6 h, while cell viability remained above 70% at 100 μM, with time-dependent cellular fluorescence consistent with nanoparticle uptake. This work presents a feasible strategy for fluorinated AIE-active copolymers as dual-mode 19F MRI/fluorescence imaging probes.
Abstract Liquid embolic agents are used for permanent vascular occlusion, but Histoacryl lacks intrinsic radiopacity and exhibits strong microcatheter adhesion. In this study, iodinated and fluorinated cyanoacrylates were investigated for liquid embolic compositions. 2-Iodoethyl 2-cyanoacrylate (IECA) had a calculated iodine concentration of 1100 mg I/mL. Among the fluorinated cyanoacrylates evaluated, 2,2,3,3,3-pentafluoropropyl 2-cyanoacrylate (PFPCA) showed the highest polymerization rate (15.77 ± 1.96 μL/s). The IECA/PFPCA blend containing 67% IECA (IF67) had an iodine concentration of 730 mg I/mL. The optimized formulation, IFO50, containing IF67 and 50% ethyl oleate, showed a polymerization rate of 0.80 ± 0.07 μL/s, an iodine concentration of 370 mg I/mL, and a microcatheter adhesion force of 2.24 ± 0.36 N. In rabbit renal artery embolization, IFO50 was visible under fluoroscopy, and post-embolization digital subtraction angiography showed no contrast-medium opacification of the treated artery. Computed tomography at 7 days showed the embolic cast in the treated kidney without apparent migration to distant organs.
Abstract Novel biomimetic surgical adhesives were prepared in this work by the straightforward incorporation of L-3,4-dihydroxyphenylalanine (DOPA) in poly(ester amide)s (PEAs). A library of DOPA-based PEAs (DOPA-PEAs) with varying compositions was successfully synthesized by solution polycondensation (SPC), while preserving the catechol functionality without requiring protection/deprotection steps. Thermal analyses revealed that introducing different hydrophilic moieties and increasing molecular weight enhanced both thermal stability and glass transition temperatures (Tg). In vitro enzymatic degradation studies demonstrated tunable biodegradability, with degradation profiles suitable for supporting the early stages of wound healing. Adhesive formulations were prepared as liquid glues and tested directly on two distinct ex vivo tissues, dermis and liver, exhibiting comparable or superior wet adhesion to the commercial cyanoacrylate reference, Dermabond. Cytocompatibility assays using human dermal fibroblasts confirmed that selected adhesives supported cell viability, proliferation, and adhesion more effectively than Dermabond. Overall, the results highlight the versatility of DOPA-PEAs as biomimetic surgical adhesives with customizable structure−property relationships, enabling strong, moisture-resistant tissue adhesion and favourable biological compatibility.
