Bis-2'-F-cGSASMP isomers encapsulated in cytidinyl/cationic lipids act as potent in situ autologous tumor vaccines.

Cancer immunotherapy has greatly improved the prognosis of tumor-bearing patients. Nevertheless, cancer patients exhibit low response rates to current immunotherapy drugs, such as PD1 and PDL1 antibodies. Cyclic dinucleotide analogs are a promising class of immunotherapeutic agents. In this study, in situ autologous tumor vaccines, composed of bis-2'-F-cGSASMP phosphonothioate isomers (FGA-di-pS-2 or FGA-di-pS-4) and cytidinyl/cationic lipids (Mix), were constructed. Intravenous and intratumoral injection of FGA-di-pS-2/Mix or FGA-di-pS-4/Mix enhanced the immunogenic cell death of tumor cells in vivo, leading to the exposure and presentation of whole tumor antigens, inhibiting tumor growth in both LLC and EO771 tumor in situ murine models and increasing their survival rates to 50% and 23%, respectively. Furthermore, the tumor-bearing mice after treatment showed potent immune memory efficacy and exhibited 100% protection against tumor rechallenge. Intravenous administration of FGA-di-pS-2/Mix potently promoted DC maturation, M1 macrophage polarization and CD8+ T cell activation and decreased the proportion of Treg cells in the tumor microenvironment. Notably, two doses of ICD-debris (generated by FGA-di-pS-2 or 4/Mix-treated LLC cells) protected 100% of mice from tumor growth. These tumor vaccines showed promising results and may serve as personalized cancer vaccinations in the future.

Transmission mode transformation of rotating controllable beams induced by the cross phase.

In this paper, complex-variable sine-Gaussian cross-phase (CVSGCP) beams are proposed, and the transmission dynamics properties of the CVSGCP beams in strongly nonlocal nonlinear media are investigated. CVSGCP beams can produce a variety of mode transformation characteristics during transmission. The roles of parameters in the sine and cross-phase terms of the initial light field expression in the evolution of light intensity modes, phase, and beam width are analyzed in detail, and it is proved that the effect of cross phase is to cause the beams to rotate. The control of different modes can be achieved by selecting suitable parameters, which have certain advantages in the practical application of CVSGCP beams. CVSGCP beams can be regarded as generalized high-order breathers because light intensity modes and beam width show periodic oscillation distribution during transmission. The typical evolution characteristics of the CVSGCP beams are verified by numerical simulation. Strongly nonlocal nonlinear optical media can be mathematically equivalent to a variety of optical systems, such as gradient index potential wells and resonant potential wells, so the conclusions in this paper can also be extended to these equivalent optical systems.

Design and Validation of a Short Novel Estradiol Aptamer and Exploration of Its Application in Sensor Technology.

The specific and sensitive detection of 17ß-estradiol (E2) is critical for diagnosing and treating numerous diseases, and aptamers have emerged as promising recognition probes for developing detection platforms. However, traditional long-sequence E2 aptamers have demonstrated limited clinical performance due to redundant structures that can affect their stability and recognition ability. There is thus an urgent need to further optimize the structure of the aptamer to build an effective detection platform for E2. In this work, we have designed a novel short aptamer that retains the key binding structure of traditional aptamers to E2 while eliminating the redundant structures. The proposed aptamer was evaluated for its binding properties using microscale thermophoresis, a gold nanoparticle-based colorimetric method, and electrochemical assays. Our results demonstrate that the proposed aptamer has excellent specific recognition ability for E2 and a high affinity with a dissociation constant of 92 nM. Moreover, the aptamer shows great potential as a recognition probe for constructing a highly specific and sensitive clinical estradiol detection platform. The aptamer-based electrochemical sensor enabled the detection of E2 with a linear range between 5 pg mL-1 and 10 ng mL-1 (R2 = 0.973), and the detection capability of a definite low concentration level was 5 pg mL-1 (S/N = 3). Overall, this novel aptamer holds great promise as a valuable tool for future studies on the role of E2 in various physiological and pathological processes and for developing sensitive and specific diagnostic assays for E2 detection in clinical applications.

Recent Advances in Tactile Sensory Systems: Mechanisms, Fabrication, and Applications.

Flexible electronics is a cutting-edge field that has paved the way for artificial tactile systems that mimic biological functions of sensing mechanical stimuli. These systems have an immense potential to enhance human-machine interactions (HMIs). However, tactile sensing still faces formidable challenges in delivering precise and nuanced feedback, such as achieving a high sensitivity to emulate human touch, coping with environmental variability, and devising algorithms that can effectively interpret tactile data for meaningful interactions in diverse contexts. In this review, we summarize the recent advances of tactile sensory systems, such as piezoresistive, capacitive, piezoelectric, and triboelectric tactile sensors. We also review the state-of-the-art fabrication techniques for artificial tactile sensors. Next, we focus on the potential applications of HMIs, such as intelligent robotics, wearable devices, prosthetics, and medical healthcare. Finally, we conclude with the challenges and future development trends of tactile sensors.

Design and synthesis of nucleotidyl lipids and their application in the targeted delivery of siG12D for pancreatic cancer therapy.

Nucleic acid drugs are attracting significant attention as prospective therapeutics. However, their efficacy is hindered by challenges in penetrating cell membranes and reaching target tissues, limiting their applications. Nucleotidyl lipids, with their specific intermolecular interactions such as H-bonding and π-π stacking, offer a promising solution as gene delivery vehicles. In this study, a novel series of nucleotide-based amphiphiles were synthesized. These lipid molecules possess the ability to self-assemble into spherical vesicles of appropriate size and zeta potential in aqueous solution. Furthermore, their complexes with oligonucleotides demonstrated favorable biocompatibility and exhibited antiproliferative effects against a broad range of cancer cells. Additionally, when combined with the cationic lipid CLD, these complexes displayed promising in vitro performance and in vivo efficacy. By incorporating DSPE-PEGylated cRGD into the formulation, targeted accumulation of siG12D in pancreatic cancer cells increased from approximately 6% to 18%, leading to effective treatment outcomes (intravenous administration, 1 mg/kg). This finding holds significant importance for the liposomal delivery of nucleic acid drugs to extrahepatic tissues.

Correction: Aptamer AS1411 interacts with the KRAS promoter/hnRNP A1 complex and shows increased potency against drug-resistant lung cancer.

[This corrects the article DOI: 10.1039/D3MD00752A.].

Aptamer AS411 interacts with the KRAS promoter/hnRNP A1 complex and shows increased potency against drug-resistant lung cancer.

G-quadruplex (G4) aptamers that can competitively binding protein with oncogene promoter G4 hold promise for cancer treatment. In this study, a neutral cytidinyl lipid, DNCA, was shown to transfect and deliver G4 aptamers (AS1411, TBA) into tumour cells, including multidrug-resistant tumour cells, and their nuclear localizations were clearly detected. Both AS1411/DNCA and TBA/DNCA showed excellent antitumour efficacies in the drug-resistant non-small cell lung cancer cell line A549/TXL at a low concentration (100 nM). Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) was identified as a new target of AS1411 and TBA. The binding affinities were measured, and the Kd values of AS1411/hnRNP A1 and TBA/hnRNP A1 were 17.5 nM and 21.1 nM, respectively. Then the expression of KRAS mRNA in A549/TXL cells was found to be higher than that in A549 cells, and KRAS mRNA was reduced by approximately 40% after administration of AS1411 or TBA in A549/TXL cells. Further, it was confirmed for the first time that AS1411 targeted not only hnRNP A1 but also the KRAS promoter/hnRNP A1 complexes. And although TBA cannot target the KRAS promoter/hnRNP A1 complexes, the biolayer interferometry (BLI) experiment showed that TBA and AS1411 have similar effects on several key proteins in tumour cells, especially hnRNP A1. Molecular docking and molecular dynamics simulation showed that AS1411 and the KRAS promoter bound to the same domain of hnRNP A1 protein, while TBA bound to another domain.