Latest ArticlesAs an extensively applied therapeutic approach to combat tumors, radiotherapy generates localized ionizing radiation to destruct tumor cells. Despite its importance in clinical oncology, radiotherapy would often cause significant organ toxicity, and its therapeutic effect is limited by tumor hypoxia. Moreover, although abscopal therapeutic effects have occasionally been observed, radiotherapy is still mostly employed as a local treatment method that could hardly control tumor metastases. In recent years, strategies involving biomaterials and nanomedicine have received increasingly high attention to enhance cancer radiotherapy. Beyond sensitizing tumors for radiotherapy via various mechanisms, many biomaterial systems with immune stimulating effects have also been introduced to boost the antitumor immunity post cancer radiotherapy. In this mini-review, we will summarize the progress of different biomaterials and nanomedicine systems in combination with radiotherapy to trigger antitumor immune responses and enhance the efficacy of immunotherapy, and discusses the perspectives and challenges of this research direction aimed at clinical translations.
Fluorescent dyes play a crucial role in fluorescence imaging and sensing technology. However, there is a dilemma that they are usually intrinsically hydrophobic which lacks of emission in water and modification with ionic groups to access water solubility may result in poor membrane permeability. Fluorescent dyes with strong fluorescence emission in both nonpolar and polar solvents are highly desirable. In this manuscript, we reported a strategy to develop fluorescent BODIPY dyes via installation of amide moiety at meso position of 1, 3, 5, 7-tetramethyl-BODIPY and discovered that N, N'-dialkylsubstituted BODIPY amides possessed highly fluorescent emission with favorable environment-insensitive properties.
Since antigen and adjuvant are rapid clearance in vivo, insufficient delivery to induce dendritic cells (DCs) maturation and cross-presentation, as well as limited migration efficiency of DCs to secondary lymph organs, greatly hinders the development of DCs-based immunotherapy. Herein, PCL-PEG-PCL polymersomes (PCEP-PS) as antigen and adjuvants delivery nanoplatforms (IMO-PS) were well-designed, which can electrostatically adsorb OVA antigen on the surface via DOTAP lipid and effectively encapsulate OVA antigen into the inner hydrophilic cavity to achieve both initial antigen exposure as well as slow and sustained antigen release, incorporate MPLA within the lipid layer to ligate with extracellular TLR4 of DCs as well as encapsulate IMQ in the hydrophobic membrane to ligate with intracellular TLR7/8 of DCs for activating synergistic immune responses via different signaling pathways. The IMO-PS significantly improved antigen uptake, promoted DCs maturation and cytokines production. DCs treated with IMO-PS could enhance migration into draining lymphoid nodes, and eventually induced antigen-specific CD8+ and CD4+ T cell responses and OVA-specific cytotoxic T lymphocyte (CTL) responses. Prophylactic vaccination of EG7-OVA tumor-bearing mice by IMO-PS + DCs significantly extended tumor-free time, effectively suppressed tumor growth, and greatly extended median survival time. The strategy may provide an effective nanoplatform for co-delivery antigen and dual-adjuvants in a spatio-temporally programmed manner for DC-based cancer immunotherapy.
Nanoscale metal organic frameworks (NMOFs) have been widely reported in biomedical field for their unique porous structure and tunable multifunctionality. However, when administrated in vivo, the protein corona will be formed on the surface of NMOFs, significantly affecting their biodistribution, pharmacokinetics and drug release. Few studies paid attention to the protein corona formation process and its influencing factors of NMOFs. As a well-established strategy for altering structure features of NMOFs, the organic ligand modification may have effect on the protein corona formation process, which is to be investigated. In this study, the zirconium (Zr)-based UIO66 was chosen as model NMOFs, the organic ligand of which was modified with amino group (-NH2) or carboxyl group (-COOH) to synthesize UIO66-NH2 and UIO66-2COOH, respectively. Bovine serum albumin (BSA) was chosen as model protein to investigate the protein corona formation process of NMOFs. The current results showed that the -COOH modification remarkably enhanced the BSA adsorption on NMOFs while -NH2 slightly decreased the protein binding affinity. These differences may be ascribed to the two different dominate protein corona formation modes, i.e., surface coating mode and porous embedded mode. The protein corona formation did not affect the crystal phase of NMOFs but increased the content of α-helix of BSA. Ultimately, upon protein corona formation, the cellular uptake of NMOFs was significantly affected. We believe our study will provide a new research paradigm to the design and applications of NMOFs.
Downregulated pro-apoptotic protein in cancer cells compromises the chemotherapy by a cytotoxic drug. Here, we report co-delivery of a pro-apoptotic protein, caspase 3 (Cas 3), and cytotoxic agent, oridonin (ORD), for synergistic cancer treatment, using a method of liposome-based anchoring and core encapsulation. First, ORD is modified with hyaluronic acid (HA) to improve its solubility. Then, the targeted co-delivery system is prepared by assembling the conjugate HA-ORD onto the Cas 3-loaded liposomes, which the surface HA can target the CD44 receptor on cancer cells. In vitro, the co-loaded liposomes (120 nm) are specifically taken up by 4T1 cells and endow a 1.5-fold increase of Cas 3. After intravenous injection into the tumor-bearing mice, the liposomes accumulate in the tumor with high efficacy and significantly inhibit tumor growth via promoting apoptosis and anti-proliferation of cancer cells. Mechanistically, the co-delivery works synergistically by upregulating the activated Cas form, cleaved-Cas 3.
Although targeted therapy and immunotherapy are now shining in the treatment of some cancers, chemotherapy is still the cornerstone of drug treatment for many cancer patients. The emergence of chemotherapy prodrugs can improve the drug activity and reduce the side effects of chemotherapy. When used, the tumor microenvironment has characteristics different from normal tissues, and the existence of the microenvironment provided a more convenient way to design responsive nanodrugs. Herein, we designed a glutathione (GSH)-responsive prodrug nanogels for enhancing tumor chemotherapy. In the nanogels of HHNP, 10-hydroxycamptothecin (HCPT) played an essential role in killing cancer cells. HCPT was jointed with a cross-linker agent with disulfide bond and was further coated with polyethylene glycol, which not only prolonged the half-life of the drug, but also made HCPT accurate transport to the tumor fractions and achieved precise and controllable release. The proposal of HHNP effectively retained the biological activity of the drug, and introduced functions such as targeting, selective release and biodegradation, which greatly improved the medical efficiency of the drug and effectively reduced the toxic and side effects. This chemotherapeutic prodrug nanogel offers a new window for constructing efficient drug delivery platform.
Fluorescence (FL) active 8-aryl guanosine derivatives were prepared and applied for cation mediated self-assembly to form the H-bonded G8-quadruplexes. The p-cyano (p-CN) and 8-anthracene (8-An) substituted guanosines were identified to give the strongest fluorescence with the formation of G8-octamers (G8) both in solution (NMR) and solid state (X-ray). This well-defined G8-octamer system has provided the first direct evidence on the self-assembled G-quadruplex fluorescence emission with aggregation-induced emission (AIE), which could be applied as the foundation for FL molecular probe design toward G-quadruplex recognition.
Since the concept of aptamer emerged, many scientists have launched a rich field of research around it. However, few nucleic acids aptamer which use cell as target can be put into practical applications. We believe that a great deal of this lies in the complexity and irreproducibility of aptamer screening experiments themselves. The complexity is due to the cumbersome processes and the technical requirements for laboratory personnel, whereas irreproducibility arises from the fact that the starting point of such screens is nucleic acid libraries with random fragments, and that different libraries directly determine the differences or even the success or failure of screening results. The complexity and irreproducibility mentioned above, in turn, lead to the inability of this experiment to unfold on a large scale, which naturally cannot lead to excellent results for practical applications. In response to this problem, our group has developed an instrument for automated screening of tumor cell nucleic acid aptamers and characterized the properties of nucleic acid aptamers obtained using this instrument in a comprehensive manner.
Stabilizing triplet excited states is important for room temperature phosphorescence (RTP) materials to achieve multifunctional applications in humid environment. However, due to the lack of preparation strategies, the realization of RTP materials in water still faces challenges. Herein, a new design strategy was presented to achieve RTP in water by confining carbonized polymer dots (CPDs) in amino functional mesoporous silica (MSNs-NH2). The as-prepared MSNs-CPDs aqueous dispersion exhibited blue afterglow, lasting more than 3 s to naked eyes. The triplet excited states were protected from non-radiative deactivation by the double-confinement effect including covalent bonding fixation and mesoporous structure confinement. The MSNs-CPDs inherited the structure of MSNs-NH2, so the stability of morphology and properties were superior to CPDs and even most of silica-based CPDs RTP materials. A water-related encryption technique demonstrated the promising application of MSNs-CPDs as smart materials in the field of information security. Besides, the possibility of potential application in ion detection was also explored.
Sulfur dioxide and its derivative sulfite widely existed in air, water as the environment pollutant. Sulfite is also commonly used as preservative and additive in fresh fruits, vegetables, wines and pharmaceutical materials. Due to sulfite is closely related with human diseases, it is very urgent for the sensitive and rapid quantification of sulfite in various samples. In our study, a turn-on near infrared (NIR) fluorescent probe (MDQ) was developed for sulfite detection based on a Michael addition reaction, with high sensitivity (LOD 4.16 nmol/L), selectivity and fast response time (400 s). Using MDQ, a quantify method for sulfite in traditional Chinese medicines (TCMs) was developed with the advantages of high precision, accuracy and convenient operation. Furthermore, according to the photophysical property of MDQ, a portable fluorescence detector is designed to quantify sulfite for TCMs and surface water in Dalian city of China. Therefore, the developed fluorescent probe MDQ and portable fluorescent detector as a rapid inspection instrument were successfully used to real-time monitor the sulfite in various complex samples.
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